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We're just a group of healthcare students learning about the epidemiology of type 2 diabetes.

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The Correlation of Age and Type 2 Diabetes

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The Correlation of Age and Type 2 Diabetes

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The American Diabetes Association found as your age increases, so does your risk of Type 2 Diabetes. Women also have higher risks than men and the rates vary among differing races and ethnicities.

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Wei Perng, Rebecca Conway, Elizabeth Mayer-Davis, Dana Dabelea; Youth-Onset Type 2 Diabetes: The Epidemiology of an Awakening Epidemic. Diabetes Care 1 March 2023; 46 (3): 490-499. https://doi.org/10.2337/dci22-0046

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Youth-Onset Type 2 Diabetes: The Epidemiology of an Awakening Epidemic

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In this narrative review, we describe the epidemiology (prevalence, incidence, temporal trends, and projections) of type 2 diabetes among children and adol

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Lifestyle habits for people with Diabetes

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Lifestyle habits for people with Diabetes

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Here is information regarding lifestyle habits that influence diabetes in people. These habits regard meal composition, meal timing, nutrient sequencing, and exercise before and after meals. These are all influences on glycemia.

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Five Evidence-Based Lifestyle Habits People With Diabetes Can Use

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Several evidence-based lifestyle habits focusing on the composition, timing, and sequence of meals and on pre- and postmeal exercise can improve diabetes management. Consuming low-carbohydrate, balanced meals and eating most carbohydrates early in…

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The 3 different types of diabetes and their symptoms

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Many people are confused about the different types of diabetes. Type 1 diabetes is usually linked to small children and young adults due to the body's inability to produce insulin. Type 2 is the pancreas slowing down the production of insulin. Gestational diabetes is where hormonal changes during pregnancy affect the mother's insulin levels.

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Why Pakistan is Consistently Among the Highest Type 2 Diabetes Affected Countries

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Why Pakistan is Consistently Among the Highest Type 2 Diabetes Affected Countries

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Type 2 diabetes prevalence in Pakistan: what is driving this? Clues from subgroup analysis of normal weight individuals in diabetes prevalence survey of Pakistan

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Type 2 diabetes mellitus (T2DM) is a global health tissue. We determined factors relating to the likelihood of developing T2DM in normal BMI individuals. This was a cross-sectional community-based representative survey, of people aged ≥20 years in…

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This article explains how the pancreas is connected to diabetes. It breaks it down in common language for us to understand how the improper function of the pancreas leads to the different types of diabetes.

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The pancreas is the organ that produces insulin. Insulin is an essential hormone for regulating blood glucose levels. Problems with the pancreas and insulin production can lead to diabetes.

Type 1 diabetes occurs when the pancreas does not make enough or any insulin. Conversely, type 2 diabetes develops when the body cannot use insulin correctly.

In this article, we look at the role of the pancreas in diabetes. We also describe complications of diabetes that relate to the pancreas and other disorders of the organ.

The pancreas digestive enzymes and sits within the abdomen, behind the stomach.

This organ also produces insulin, a hormone that helps regulate blood glucose levels. The cells that produce insulin are called beta cells and sit in the islets of Langerhans, a set of structures within the pancreas.

Insulin helps the body use carbohydrates in food for energy and helps transport glucose from the blood into the body's cells. Glucose provides the cells with the energy they need to function.

If there is insufficient insulin in the body, cells can no longer take up glucose from the blood. As a result, levels of glucose in the blood rise. A doctor may refer to this as having high blood glucose, or hyperglycemia.

Hyperglycemia is responsible for most of the symptoms and complications of diabetes.

The main feature of diabetes is high blood glucose. This results from insufficient insulin production or function, which can result from issues with the pancreas.

People with diabetes experience high or low blood glucose levels at different times, depending on what they eat, how much they exercise, and whether they take insulin or diabetes medication.

Type 1 and type 2 diabetes both the pancreas.
What are the treatment options for diabetes?
Type 1 diabetes

Type 1 diabetes occurs when the pancreas does not make enough, or any, insulin. Without this hormone, the cells cannot get enough energy from food.

This form of diabetes results from the body's immune system attacking the insulin-producing beta cells in the pancreas. The beta cells become damaged and, over time, the pancreas stops producing enough insulin to meet the body's needs.

People with type 1 diabetes can rebalance their blood glucose levels by receiving insulin injections or wearing an insulin pump every day.

Doctors once called this type "juvenile diabetes" because it often develops during the childhood or teenage years.

There is no clear cause of type 1 diabetes. Some suggests that it results from genetic or environmental factors. Almost 1.9 million people in the United States are living with type 1 diabetes.

Type 2 diabetes

This type of diabetes occurs when the body builds up a resistance to insulin. While the pancreas may still produce the hormone, the body's cells cannot use it effectively.

As a result, the pancreas produces more insulin to meet the body's needs and is often unable to keep up with the increased demand.

With too little insulin in the body, diabetes develops. Over time, the beta cells become damaged and may stop producing insulin altogether.

As with type 1 diabetes, type 2 diabetes can cause high blood glucose levels and prevent the cells from getting enough energy.

Type 2 diabetes may result from genetics and family history. Lifestyle factors, such as obesity, lack of exercise, and dietary choices, also play a role. Treatment often involves becoming more active, making dietary changes, and taking some prescription medications.

A doctor may be able to detect type 2 diabetes early, in a stage called prediabetes. A person with prediabetes may be able to prevent or delay the onset of the condition by making changes to their diet and exercise routines.
What is a prediabetes diet?
Gestational diabetes

Pregnancy can cause type 2 diabetes, known as gestational diabetes, which can result from complications during pregnancy and delivery.

After a person gives birth, gestational diabetes usually goes away, though it may increase the risk of developing type 2 diabetes later in life.

Pancreatitis causes inflammation in the pancreas, and there are types. The first is acute pancreatitis, where symptoms come on suddenly and last for a few days. The second is chronic pancreatitis, a long lasting condition where symptoms come and go for several years.

Chronic pancreatitis can damage the cells in the pancreas, potentially causing diabetes.

Pancreatitis is treatable, but severe cases can be life threatening and require hospitalization.

Symptoms of pancreatitis include:

nausea, vomiting, or both

pain in the upper abdomen that can radiate toward the back

pain that feels worse after eating

abdominal tenderness

a racing pulse

According to the Pancreatic Cancer Action Network, people who have lived with diabetes for 5 or more years are between 1.5 and two times more likely to develop pancreatic cancer. This type of cancer can affect blood glucose levels.

The National Cancer Institute says the onset of type 2 diabetes in people without risk factors for diabetes may sometimes indicate this disease.

For people with diabetes, having blood glucose levels that unexpectedly become harder to manage could also be a sign of pancreatic cancer.

The link between diabetes and pancreatic cancer is complex. Diabetes increases the risk of developing this type of cancer, while pancreatic cancer can sometimes lead to diabetes.

In its early stages, this type of cancer can cause no symptoms. Doctors often diagnose it when it is more advanced.

Other risk factors for pancreatic cancer :

having obesity

being over 55 years of age

having cirrhosis or a Heliobacter pylori infection

smoking

exposure to chemicals in certain environments, such as the drycleaning or metalwork industries

being male

a family history of the disease

being African American

Research has shown that Black people are more likely to develop pancreatic cancer than white individuals and that the survival rate is also lower. One reason for this could be disparities in access to healthcare and socioeconomic status.

People with cystic fibrosis can develop a type of insulin-requiring diabetes known as cystic fibrosis-related diabetes (CFRD).

In a person with cystic fibrosis, sticky mucus causes scar tissue to form on the pancreas. This scarring can prevent the organ from producing enough insulin.

A person with CFRD may not have the typical signs and symptoms of diabetes. For example, they are less likely to experience increased thirst and urination. For this reason, screening for CFRD is routine for people with cystic fibrosis.

Diabetes results from problems with the pancreas and insulin, as insufficient insulin can lead to high blood glucose.

Over time, persistently high glucose levels can cause serious complications. Monitoring and managing blood glucose levels can help reduce the risk of complications.

Diabetes can also occur with some chronic conditions, such as pancreatitis and cystic fibrosis.

A person could help prevent type 2 diabetes by not smoking if applicable, maintaining a moderate weight, eating a nutritious diet, and exercising regularly.

Both type 1 and type 2 diabetes are manageable health conditions, and lifestyle modifications and medications can help people manage their symptoms.

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Diabetes and the pancreas: Insulin, complications, and function

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The pancreas plays a role in diabetes because it produces insulin and helps regulate blood sugar levels. We look into the links between diabetes and the pancreas.

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Here is a information on specifically how type 2 diabetes damages the kidney and causes secondary diseases and illnesses.

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Over time, uncontrolled type 2 diabetes can overwork your kidneys and cause kidney disease. Find out how these kidney problems happen and how you can slow it down.

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Type 2 diabetes leading to kidney failure

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Type 2 diabetes leading to kidney failure

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This gives the pathophysiology of how type 2 diabetes leads to chronic kidney disease and kidney failure.

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Chronic kidney disease (CKD) is common in people with diabetes.

CKD often develops slowly and with few symptoms.

If you have diabetes, get your kidneys checked regularly to treat CKD early.

How CKD develops

Chronic kidney disease often develops slowly and with few symptoms. Many people don't realize they have CKD until it's advanced. At that point, they need dialysis (a treatment that filters the blood) or a kidney transplant to survive.

If you have diabetes, get your kidneys checked regularly. This is done by your doctor with simple blood and urine tests. Regular testing is your best chance for identifying CKD early if you do develop it. Early treatment is most effective and can help prevent additional health problems.

CKD is common in people with diabetes. Approximately 1 in 3 adults with diabetes has CKD. Both type 1 and type 2 diabetes can cause kidney disease.

How diabetes causes CKD

Each kidney is made up of millions of tiny filters called nephrons. Over time, high blood sugar from diabetes can damage blood vessels in the kidneys and nephrons. Many people with diabetes also develop high blood pressure, which can damage kidneys too.

CKD takes a long time to develop and usually doesn't have any signs or symptoms in the early stages. You won't know you have CKD unless your doctor checks you for it.

Tips for healthy kidneys

You can help keep your kidneys healthy by managing your blood sugar, blood pressure, and cholesterol levels. This is also very important for your heart and blood vessels. High blood sugar, blood pressure, and cholesterol levels are all risk factors for heart disease and stroke.

Keep your blood sugar levels in your target range as much as possible.

Get an A1C test at least twice a year. Ask your doctor how often is right for you.

Keep your blood pressure below 140/90 mm Hg (or the target your doctor sets).

Stay in your target cholesterol range.

Eat foods lower in sodium.

Eat more fruits and vegetables.

Be physically active.

Take your medicines as directed.

Prediabetes and CKD

If you have prediabetes, taking action to prevent type 2 diabetes is an important step in preventing CKD. CDC's National Diabetes Prevention Program can help you create the healthy lifestyle habits needed to prevent type 2 diabetes. Find a program in your community or online.

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Regular testing is your best chance for finding CKD early when treatment is most effective.

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Studies at the CDC show that the brain can actually be significantly affected by Type 2. Memory, mood shifts, weight gain, and more can occur if type 2 diabetes continues without help from a physician.

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Learn about the connection between diabetes and the brain and how to keep your brain healthy.

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Greater risk of dementia, Alzheimer's, and stroke

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Greater risk of dementia, Alzheimer's, and stroke

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Your cognitive health can rapidly decline when dealing with type 2 diabetes. Dementia, Alzheimer's, and even strokes are possible if your blood sugar becomes too high or too low.

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Type 2 Diabetes May Accelerate Cognitive Decline, Research Shows

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Learn how type 2 diabetes could affect your brain--and what you can do to keep it sharp.

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The organs affected by diabetes include the kidneys, brain, pancreas, liver, skeletal muscles, and intestines. Beta cell dysfunction and insulin resistance combined lead to hyperglycemia being amplified and type 2 diabetic concerns becoming more prevalent.

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1. Introduction

Type 2 Diabetes Mellitus (T2DM) is one of the most common metabolic disorders worldwide and its development is primarily caused by a combination of two main factors: defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond to insulin [ 1]. Insulin release and action have to precisely meet the metabolic demand; hence, the molecular mechanisms involved in the synthesis and release of insulin, as well as the insulin response in tissues must be tightly regulated. Therefore, defects in any of the mechanisms involved can lead to a metabolic imbalance that leads to the pathogenesis of T2DM.

This review analyses the key aspects of T2DM, as well as the molecular mechanisms and pathways implicated in insulin metabolism and associations between T2DM and cardiovascular pathophysiology. In this review, we describe the global trends of T2DM, the roles of major risk factors, in particular, obesity, lifestyle factors, genetic predispositions, gut dysbiosis, epigenetics and mitochondrial deregulation. We highlight physiological and molecular mechanisms leading to T2DM and its complications.

2. Type 2 Diabetes Mellitus: Background and Epidemiology

According to the World Health Organization (WHO) diabetes mellitus is a chronic, metabolic disease characterized by elevated levels of blood glucose, which leads over time to damage to the heart, vasculature, eyes, kidneys and nerves. Over 90% of diabetes mellitus cases are T2DM, a condition marked by deficient insulin secretion by pancreatic islet β-cells, tissue insulin resistance (IR) and an inadequate compensatory insulin secretory response [ 2, 3]. Progression of the disease makes insulin secretion unable to maintain glucose homeostasis, producing hyperglycaemia. Patients with T2DM are mostly characterized by being obese or having a higher body fat percentage, distributed predominantly in the abdominal region. In this condition, adipose tissue promotes IR through various inflammatory mechanisms, including increased free fatty acid (FFA) release and adipokine deregulation. The main drivers of the T2DM epidemic are the global rise in obesity, sedentary lifestyles, high caloric diets and population aging, which have quadrupled the incidence and prevalence of T2DM [ 4, 5].

The organs involved in T2DM development include the pancreas (β-cells and α-cells), liver, skeletal muscle, kidneys, brain, small intestine, and adipose tissue [ 6]. Evolving data suggest a role for adipokine dysregulation, inflammation, and abnormalities in gut microbiota, immune dysregulation, and inflammation have emerged as important pathophysiological factors [ 7].

Epidemiological data show alarming values that predict a worrisome projected future for T2DM. According to the International Diabetes Federation (IDF), in 2019, diabetes caused 4.2 million deaths; and 463 million adults aged between 20 and 79 years old were living with diabetes, a number that will likely rise up to 700 million by 2045. Diabetes was the underlying cause of at least 720 billion USD in health expenditure in 2019. Additionally, the true disease burden of T2DM is likely an underrepresentation as 1 in 3 diabetic people were underdiagnosed, equivalent to 232 million people. The greatest number of people suffering from diabetes are aged between 40 and 59 years old. Incidence and prevalence of T2DM vary according to geographical region, with more than 80% of patients living in low-to-middle-income countries, which poses additional challenges in effective treatment. Patients with T2DM have a 15% increased risk of all-cause mortality compared with people without diabetes with cardiovascular disease (CVD) as the greatest cause of morbidity and mortality associated with T2DM [ 8]. The association of diabetes with increased risk of coronary heart disease (hazard ratio [HR] 2.00; 95% CI 1.83-2.19), ischaemic stroke (HR 2.27; 1.95-2.65), and other vascular disease-related deaths (HR 1.73; 1.51-1.98) has been shown in a meta-analysis [ 9].

Epidemiology of T2DM is affected both by genetics and the environment. Genetic factors exert their effect following exposure to an environment characterized by sedentary behavior and high-calorie intake. Common glycaemic genetic variants for T2DM have been identified by genome-wide association studies, but these only account for 10% of total trait variance, suggesting that rare variants are important [ 10]. People of different ethnic origins may have different specific phenotypes that increase predisposition to clusters of CVD risk factors, including hypertension, insulin resistance, and dyslipidemia [ 11].

3. Risk Factors and Pathophysiology

T2DM risk factors include a complex combination of genetic, metabolic and environmental factors that interact with one another contributing to its prevalence. Although individual predisposition to T2DM due to non-modifiable risk factors (ethnicity and family history/genetic predisposition) has a strong genetic basis, evidence from epidemiological studies suggests that many cases of T2DM can be prevented by improving the main modifiable risk factors (obesity, low physical activity and an unhealthy diet) [ 12, 13].

3.1. Ethnicity and Family History/Genetic Predisposition

Globally, the incidence and prevalence of T2DM are found to vary widely depending on ethnicity and geographical region with Japanese, Hispanics and Native Americans having the highest risks [ 14, 15, 16]. It has been shown higher incidence rates in Asians compared with a White American population [ 17, 18], and white population in the UK, [ 19], where the highest risk is among the black population [ 20]. Whilst no clear reasons have been found, contributing factors such as modern lifestyle factors (which promote obesity), socioeconomic and direct genetic propensity or gene environmental interactions have been postulated.

3.2. Obesity, Low Physical Activity and Unhealthy Diet

Obesity (body-mass index [BMI]≥30 kg/m ²) is the strongest risk factor for T2DM [ 26, 27] and is associated with metabolic abnormalities resulting in IR [ 28]. There exist an inverse linear relationship between BMI and the age at diagnosis of T2DM [ 29]. The exact mechanisms by which obesity induces T2DM and IR remain to be elucidated; however, numerous factors have shown a significant role in the development of this pathological process, which involves both cell-autonomous mechanisms and inter-organ communications.

A sedentary lifestyle is another risk factor for T2DM as shown by the Women's Health Study and in the Kuipio Ischemic Heart Disease Risk Factor Study, which showed a reduction of 34% and 56% reduction of developing T2DM in participants walking 2-3 h a week or at least 40 min a week, respectively [ 30, 31]. There are three primary benefits of physical activity on the delay of T2DM onset. First, the contraction of skeletal muscle cells induces an increase in blood flow into the muscle, enhancing glucose uptake from plasma [ 32]. Second, physical activity reduces the notorious intra-abdominal fat, which is a known risk factor that promotes IR [ 33]. Finally, moderate-intensity exercise has been shown to improve glucose uptake by 40% [ 34]. Physical activity improves glucose uptake and insulin sensitivity but it can also improve or even reverse inflammation and oxidative stress, which are T2DM predisposing factors [ 32].

3.3. Pathophysiology

Regarding the pathophysiology of the disease, a malfunctioning of the feedback loops between insulin action and insulin secretion results in abnormally high glucose levels in blood [ 2]. In the case of β-cell dysfunction, insulin secretion is reduced, limiting the body's capacity to maintain physiological glucose levels. On the other hand, IR contributes to increased glucose production in the liver and decreased glucose uptake both in the muscle, liver and adipose tissue. Even if both processes take place early in the pathogenesis and contribute to the development of the disease, β-cell dysfunction is usually more severe than IR. However, when both β-cell dysfunction and IR are present, hyperglycaemia is amplified leading to the progression of T2DM [ 35, 36].

4. Mechanisms Leading to T2DM and Pathophysiology

4.1. Insulin Secretion: Physiological and Dysfunctional Mechanisms Leading to T2DM

4.1.1. β-Cell Physiology

To safeguard proper β-cell function, cellular integrity must be ensured and the mechanisms and pathways implicated in the physiology of β-cell must be tightly regulated [ 35].

β-cells are responsible for insulin production, which is synthesized as pre-proinsulin. In the maturation process, pre-proinsulin undergoes a conformational modification carried out with the help of several proteins in the endoplasmic reticulum (ER) to yield proinsulin [ 37]. Afterwards, proinsulin is translocated from the ER to the Golgi apparatus (GA), entering into immature secretory vesicles and being cleaved into C-peptide and insulin [ 38, 39].

Once matured, insulin is stored in granules until insulin release is triggered. Insulin release is primarily triggered by a response to high glucose concentrations. It is worth noting that some other factors can also induce insulin release such as amino acids, fatty acids and hormones [ 40]. When circulating glucose levels increase, β-cells take in glucose mainly through the glucose transporter 2 (GLUT2), a solute carrier protein that also works as a glucose sensor for β-cells. Once glucose enters, glucose catabolism is activated, increasing the intracellular ATP/ADP ratio, which induces the closing of ATP-dependant potassium channels in the plasma membrane. This leads to membrane depolarization and opening of the voltage dependant Ca ²⁺ channels, enabling Ca ²⁺ to enter the cell. The rise in the intracellular Ca ²⁺ concentration triggers the priming and fusion of the secretory insulin-containing granules to the plasma membrane, resulting in insulin exocytosis [ 38, 40, 41, 42] ( Figure 1 A).

Additionally, Ca ²⁺ signals can be amplified by the RY receptors (RYR) and may play important roles in stimulus- insulin secretion coupling by virtue of their strategic locations within the cell and their ability to mediate Ca ²⁺ induced Ca ²⁺ release (CICR). RYR amplifies Ca ²⁺ signals when the channel is sensitized by messenger molecules generated from the nutrient metabolism or ligand-binding and are involved in the amplification of insulin secretion [ 43] ( Figure 1 A).

Nevertheless, other cell signals can also assist or enhance insulin release from β-cells. Among them, cAMP might be the most important messenger potentiating insulin release. Accumulated evidence suggests that cAMP induces insulin-containing secretory vesicle mobilization by depleting intracellular Ca ²⁺ reservoirs, thereby increasing intracellular Ca ²⁺ concentrations [ 44]. There is also compelling evidence that extracellular ATP is another important regulator of β-cell function. It is well-documented that β-cells release ATP through exocytosis of insulin granules upon glucose stimulation. Purinergic signaling via P2Y and P2X purinergic receptors stimulates Ca ²⁺ mobilization and regulates insulin exocytosis also independently of glucose. P2Y purinoreceptors have been reported to be coupled to G-proteins [ 45, 46] whereas P2X-type receptors are ATP-activated ligand-gated ion channels non-selective for cations [ 47]. In the case of P2Y receptors, it has been proposed that insulin release could be mediated by intracellular Ca ²⁺ mobilization in response to inositol-1,4,5-trisphosphate (IP3) formation that triggers the release of Ca ²⁺ from ER stores, which amplifies the exocytosis-triggering Ca ²⁺ signal [ 48, 49] ( Figure 1 A).

4.1.2. Mechanisms Leading to β-Cell Dysfunction

β-cell dysfunction has been traditionally associated with β-cell death [ 50]. However, recent evidence suggests that the dysfunction of β-cells in T2DM might be due to a more complex network of interactions between the environment and different molecular pathways implicated in cell biology [ 51]. In an excessive nutritional state, similar to that found in obesity, hyperglycemia and hyperlipidemia are often present, favoring IR and chronic inflammation. Under these circumstances, β-cells, due to differences in their genetic susceptibility, are subject to toxic pressures including inflammation, inflammatory stress, ER stress, metabolic/oxidative stress, amyloid stress, with the potential of ultimately leading to a loss of islet integrity [ 50].

An excess of FFAs and hyperglycemia lead to β-cell dysfunction by inducing ER stress through the activation of the apoptotic unfolded protein response (UPR) pathways [ 52]. In fact, lipotoxicity, glucotoxicity and glucolipotoxicity occurring in obesity, induce metabolic and oxidative stress that leads to β-cell damage [ 51]. Stress derived from high levels of saturated FFAs can activate the UPR pathway by several mechanisms including inhibition of the sarco/endoplasmic reticulum Ca ²⁺ ATPase (SERCA) responsible for ER Ca ²⁺ mobilization; activation of IP3 receptors or direct impairment of ER homeostasis. In addition, sustained high glucose levels increase proinsulin biosynthesis and islet amyloid polypeptides (IAAP) in β-cells, leading to the accumulation of misfolded insulin and IAAP and increasing the production of oxidative protein folding-mediated reactive oxygen species (ROS) [ 52]. These effects alter physiological ER Ca ²⁺ mobilization and favor proapoptotic signals, proinsulin mRNA degradation and induce interleukin (IL)-1 β release that recruits macrophages and enhances local islet inflammation [ 51] ( Figure 1 B).

As previously mentioned, insulin secretion has to be finely regulated to precisely meet metabolic demand. For that reason, proper islet integrity must be conserved in order to allow β-cells to respond to metabolic needs. Under pathogenic conditions, the mechanism described above can ultimately lead to disruption of islet integrity/organization, impairing optimal cell-to-cell communication within pancreatic islets, contributing to poor regulation of insulin and glucagon release and ultimately exacerbating the hyperglycemia. Defects in the synthesis of any insulin precursors, or insulin itself, as well as disruption of the secretion mechanism, can lead to insulin secretory dysfunction, the primary driver of β-cell failure, and a foundation of T2DM. For instance, reduced expression in the GLUT2 glucose transporter would affect the downstream signaling pathway [ 53], while failure in the folding of proinsulin is another finding commonly linked to deficient insulin production and diabetes [ 54].

4.1.3. Pathological Conditions Perpetuating T2DM

Nutritional Factors

Physical Activity

Gut Dysbiosis

Mitochondrial Dysfunction

5. Insulin Resistance

IR refers to a decrease in the metabolic response of insulin-responsive cells to insulin or, at a systemic level, an impaired/lower response to circulating insulin by blood glucose levels [ 153]. There are three broad categories of IR or insulin-deficient conditions: (1) diminished insulin secretion by β-cells; (2) insulin antagonists in the plasma, due either to counter-regulatory hormones or non-hormonal bodies that impair insulin receptors or signaling; and (3) impaired insulin response in target tissues [ 154]. The action of insulin is influenced by the interplay of additional molecules including growth hormone and IGF-1 in the fed state. While fasting, the insulin response is mitigated by glucagon, glucocorticoids and catecholamines in order to prevent insulin-induced hypoglycemia. The ratio of insulin/glucagon plays a major role in this regulation, since it determines the relative degree of phosphorylation of downstream enzymes in the regulatory signaling pathways. While catecholamines promote lipolysis and glycogenolysis, glucocorticoids promote muscle catabolism, gluconeogenesis and lipolysis. Hence, excessive secretion of these hormones may be responsible for inducing IR [ 155, 156]. Regarding the last category, there are three main extra-pancreatic insulin-sensitive organs that play major roles in the aforementioned processes: skeletal muscle, adipose tissue and liver. A defective action of insulin in these tissues often precedes the development of systemic IR, thus progressively leading T2DM.

5.1. Skeletal Muscle

Skeletal muscle IR is considered to be the most important extra-pancreatic factor in the development of T2DM [ 157]. Under physiological conditions, insulin stimulates muscle glycogen synthesis by enhancing glucose uptake from plasma. There are three primary rate-limiting factors implicated in glucose uptake and glycogen synthesis: glycogen synthase, hexokinase and the glucose transporter GLUT4 [ 158]. Upon insulin binding to insulin receptor (INSR) in muscle cells, GLUT4 translocates from intracellular compartments (early endosomes (EE), endosomal recycling compartment (ERC) and trans-Golgi network (TGN)) to the plasma membrane. This process allows glucose uptake and reduces circulating glucose levels [ 159].

5.2. Adipose Tissue

Adipose tissue is a metabolically dynamic tissue capable of synthesizing a wide range of biologically active compounds that regulate metabolic homeostasis at a systemic level [ 163]. Indeed, adipose tissue participates in a broad range of biological processes involving, among others, immunity, coagulation, angiogenesis, fibrinolysis, reproduction, vascular tone control, appetite regulation, body weight homeostasis and glucose and lipid metabolism [ 164].

Insulin acts on adipose tissue in two different ways: (1) stimulating glucose uptake and triglyceride synthesis; and (2) suppressing triglyceride hydrolysis and inducing the uptake of FFA and glycerol from circulation [ 165]. In the fed state, GLUT4 allows uptake of glucose from the bloodstream into adipocytes, activating glycolysis in which glycerol-3-phospate (glycerol-3-P) is produced and incorporated into lipogenic pathways. Glycerol-3-P, along with the fatty acids coming from VLDLs, are esterified, forming triacylglycerol (TGA) that is stored in lipid droplets. During metabolic stress, TGA droplets the adipocyte are depleted, in order to provide FFA to be used as an energy source in other tissues.

An impaired response to insulin stimulation by adipose tissue is known as adipose IR (Adipose-IR). Adipose-IR can lead to impaired suppression of lipolysis, impaired glucose uptake, and enhanced FFA release into plasma even in the presence of high insulin levels [ 166]. Among the signaling elements affected by adipose-IR, we found that defective AKT activation impairs GLUT4 translocation to the membrane and promotes the activation of lipolytic enzymes that aggravate hyperglycemia [ 153]. Adipose-IR, as mentioned before, is associated with glucose intolerance and elevated release of FFA into a plasma that accumulates in other tissues such as muscle or liver. In the case of the liver, FFA accumulation results in impaired insulin signaling that promotes hepatic gluconeogenesis and impairs the glucose-stimulated insulin response, inducing T2DM development.

5.3. Liver

In the liver, insulin does not only regulate glucose production/utilization but also affects lipid metabolism more broadly. When circulating glucose levels increase and insulin is secreted by pancreatic β-cells, insulin binding to liver INSR induces autophosphorylation of the receptor. Consequently, insulin receptor substrates (IRSs) are recruited and phosphorylated. In turn, IRSs activate PI3K, which phosphorylates phosphatidylinositol (4,5)-bisphosphate (PIP2), generating phosphatidylinositol (3,4,5)-triphosphate (PIP3). PIP3 then activates PDK1, which phosphorylates AKT. In addition, AKT is phosphorylated by mTORC2. Once AKT is fully activated, it participates in several downstream pathways that regulate multiple metabolic processes including glycogen synthesis, gluconeogenesis, glycolysis and lipid synthesis [ 169].

In physiological states, the combined action of glucagon and insulin allows the precise regulation of hepatic glucose output. While glucagon induces hepatic glucose production, insulin acts as a potent inhibitor of glucose production when its concentration in the blood is elevated [ 170]. The effect of insulin on hepatic glucose production is due to both direct and indirect mechanisms. However, the relative importance of each of these mechanisms remains unclear [ 171].

Similar to the case in insulin-sensitive tissues, in states of IR, physiologic levels of circulating insulin are insufficient to elicit the appropriate insulin response in hepatic cells [ 176]. In the liver, IR impairs glycogen synthesis, fails to suppress glucose production, enhances lipogenesis, and increases the synthesis of proteins such as the proinflammatory CRP. In fact, the abnormal production of proinflammatory proteins such as adipocytokines and cytokines, combined with conditions such as oxidative stress, can lead to an inflammatory state responsible for altered insulin response by the liver [ 175].

6. T2DM Outcomes/Complications: Cardiovascular Risk

As described in the previous sections, T2DM is a multisystem disease with a strong correlation with CVD development [ 177]. T2DM leads to a two- to four-fold increase in the mortality rate of adults from heart disease and stroke and is associated with both micro- and macro-vascular complications, the latter consisting of accelerated atherosclerosis leading to severe peripheral vascular disease, premature coronary artery disease (CAD) and increased risk of cerebrovascular diseases [ 178, 179, 180]. These factors lead to T2DM being considered a significant risk factor for CVD [ 181], likely through the involvement of several molecular mechanisms and pathological pathways. These include the role of IR in atherosclerosis, vascular function, oxidative stress, hypertension, macrophage accumulation and inflammation [ 182, 183, 184, 185]. The following sections describe in detail the main factors implicated in cardiovascular risk outcomes from T2DM and the interactions between them ( Figure 6).

6.1. Diabetic Dyslipidaemia and Atherosclerosis Development

Dyslipidaemia is a common feature of T2DM, and increases the incidence of atherosclerosis and mortality of diabetic patients [ 186]. The hallmark of diabetic dyslipidemia is a characteristic dyslipidaemic profile consisting of elevated TG, TG-rich lipoproteins (TRLs), small dense LDLs (sdLDL), and reduced HDL levels [ 187, 188, 189]. Although the pathophysiology of dyslipidemia in T2DM is not completely characterized, several factors such as hyperglycemia, insulin resistance, hyperinsulinemia, abnormalities in adipokines and adipocytokines have been implicated [ 190]. Epidemiological studies indicate that TG-rich lipoproteins and their remnants contribute to atherogenesis and CVD risk [ 191, 192, 193, 194, 195] and experimental studies indicated a connection between cholesterol deposition and inflammation as a result of TRLs entry into the artery wall [ 196, 197]. TRLs consist of a great variety of nascent and metabolically modified lipoprotein particles including intestine-derived apoB48 (chylomicrons and chylomicron remnants) and liver-derived apoB100 (VLDL and its remnants). TRLs are highly heterogeneous in size, density, and apolipoprotein composition [ 198].

Mechanisms Leading to T2DM Dyslipidemia and Atherosclerosis

Increased hepatic TG content present in T2DM patients leads to elevated hepatic production of VLDL and normal or slightly elevated LDL-C levels, most commonly sdLDLs enriched in TG [ 189, 201]. One of the primary abnormalities in IR is impaired adipose tissue fat storage, resulting from insulin's inability to inhibit hormone-sensitive lipase (HSL). This results in constitutive FFA release from the intracellular TG stores of adipocytes. The released FFAs are taken up by hepatocytes, where they can be directed to the mitochondria and undergo β-oxidation; be re-assimilated into TG to assemble new VLDL particles; shifted to gluconeogenesis resulting in a worsening of hyperglycemia; or stored as TG leading to hepatic steatosis.

The dominant feature of diabetic dyslipidemia is the increased production rate of VLDL-apoB100 by the liver, mainly VLDL1, which is related to insulin sensitivity indices [ 202]. This highlights the role of insulin on VLDL assembly and secretion by hepatocytes [ 203]. Insulin plays a role in almost all the steps of VLDL assembly and secretion. It is known that insulin inhibits the transcription of Mttp, the gene coding for the microsomal transfer protein (MTP), the protein responsible for assembling TG with apoB100 [ 204]. MTP facilitates concerted lipid transfer and apoB100 folding as it enters the ER lumen and lipidation determines the amount of the active pool of apoB100 [ 205]. Lipidation of apoB100 is a co-translational event and a rate-limiting step of apoB100 mRNA stability thus low availability of TG leads to apoB100 degradation. The addition of TG to apoB100 generates nascent VLDL particles that are transported to the GA by Sar2/COPII-containing vesicles. Within the GA, VLDL maturation occurs in a process promoted by the phospholipase D1 (PLD1) [ 203]. Therefore, in insulin-resistant condition, MTP expression and activity is increased thus contributing to raising apoB100 lipidation and to its rescue from degradation. Indeed, IR leads to a loss of the acute insulin-mediated inhibition of apoB100 secretion [ 205].

Availability of TGs within hepatocytes is important for VLDL synthesis [ 206] and the liver uses both de novo synthesized FAs and extra-hepatic FFAs as a substrate for TG synthesis [ 207]. De novo lipogenesis occurs primarily in the fed state in which the expression of lipogenic genes is regulated by the sterol regulatory element-binding protein (SREBP). The SREBP-1c isoform up-regulates almost all the enzymes involved in FA synthesis as well as enzymes that supply acetyl-CoA units and reducing equivalents to the pathway [ 208]. Insulin regulates SREBP-1c, which explains the lipogenic effect of chronic hyperinsulinemia [ 208]. FFAs derived from adipose tissue is also a major source of liver TGs and VLDL production. As mentioned above, T2DM is characterized by increased production of FFAs by adipose tissue [ 207]. Therefore, in IR, an increase in TG lipolysis in adipose tissue and FFA influx serves as another source of lipid to the liver [ 207].

The lower HDL concentration and modified composition of HDL have an important impact in diminishing the particle capacity of inducing cholesterol efflux from the cells, which is the first step in reverse cholesterol transport (RCT) [ 218]. The impaired RCT activity has been associated with increased risk of CAD [ 219] and with flow-mediated vasodilation in T2DM patients [ 220].

Atherosclerosis is accelerated by the increased permeability of sdLDL into the subendothelial space ( Figure 7) [ 221, 222]. SdLDL particles are characterized by a lower affinity for LDLR due to conformational rearrangements occurring in apoB100 as the particle decreases in volume and size [ 223]. Furthermore, sdLDL particles are more susceptible to oxidation and thus avidly scavenged by activated macrophages in the subendothelial space, giving rise to foam cells [ 224]. In addition, sdLDL particles show increased proteoglycan binding and facilitated entry into the arterial wall, increased arterial retention, and a longer half-life [ 225]. sdLDL particles are also more likely to be glycated, more resistant to breakdown, and more susceptible to oxidation by free radicals [ 226].

There is an insulin response element in the gene for apoA-I, the primary apolipoprotein constituent of HDL particles [ 227, 228]. As the liver becomes more insulin resistant, less apoA-I is produced and there is less HDL biogenesis. Adipocytes express the ATP-binding membrane cassette transport protein A1 (ABCA1). IR downregulates the expression of ABCA1 on the surface of adipocytes and reduces HDL formation by these cells [ 229, 230, 231]. Chylomicrons are enriched with apoA-I. IR reduces the release of this apoA-I into the serum by inhibiting LPL. In addition, within the milieu of IR of diabetes, HDL particle concentrations are not only quantitatively reduced, but also tend to be dysfunctional and unable to perform their primary functions, including reversal of cholesterol transport and inhibition of oxidative and inflammatory phenomena [ 232].

Diabetic dyslipidemia acts in concert with other metabolic and vascular abnormalities to further compound vascular risk. Chronic hyperglycemia induces endothelial dysfunction through a variety of mechanisms such as by reducing vasodilation, increasing vasoconstriction, increasing exposure to free radicals and impairing endothelial cell function, with a net effect of facilitating pro-atherogenic conditions [ 238]. Increased activity of the renin-angiotensin axis has also been found to further increase oxidative stress [ 239].

6.2. Impaired Endothelial Function and Atherosclerosis Development

Endothelium plays an important role in the regulation of vascular tone and structure through a balanced release of endothelial-derived relaxing and contracting factors. This balance is altered in T2DM leading to alteration of the physicochemical properties of the vascular wall via endothelial dysfunction, oxidative stress, platelet hyperreactivity, and inflammation [ 240, 241]. These abnormalities lead to enhanced vasoconstriction, development of atherosclerosis, and favored thrombus formation [ 179, 180].

6.2.1. Mechanisms Leading to Endothelial Dysfunction in T2DM

Vascular endothelial cells are particularly susceptible to developing intracellular hyperglycemia because glucose diffuses passively through their plasma membrane. In T2DM, the excess of glucose can be metabolized in the sorbitol pathway to sorbitol and fructose by aldose reductase, which activates the aldose reductase secondary metabolic pathway, with concomitant oxidation of NADPH to NADP⁺ and reduction of NAD⁺ to NADH. NADPH depletion and an increased NADH/NAD⁺ cytosolic ratio leads to a change in redox potential that accelerates glycolysis and increases de novo synthesis of DAG [ 242]. As a result, protein kinase C (PKC) is activated, nitric oxide (NO) is reduced. These effects cause vascular permeability and increase contractility. Simultaneously, the increased NADH/NAD⁺ ratio also results in higher production of O ₂−, LDL oxidation, cytotoxic effects on endothelial cells and reduced NO availability, leading to endothelial dysfunction [ 241, 242].

The overproduction of aldoses by the sorbitol pathway promotes protein glycosylation that yields the formation of the stable Amadori products (such as glycosylated hemoglobin) and AGEs. AGEs are associated with several molecules that augment oxidant activity and consequently the production of ROS, which increases oxidative stress and prevents the release of NO, resulting in vascular lesions. AGEs may also reduce endothelium-derived NO bioavailability and activity, further compromising vascular activity [ 243]. In addition, AGEs can trigger an inflammatory and pro-coagulant state and can cause endothelial activation through the induction of receptor-mediated gene transcription. AGE binding to the RAGE-receptor, nuclear transcription factor NF-κB [ 242, 243] is activated leading to transcription of endothelin-1, VCAM-1, ICAM-1, E-selectin, thrombomodulin, TF, vascular endothelial growth factor (VEGF), IL-1, IL-6, and TNF-α [ 242, 244]. Increased expression of inflammatory and adhesion molecules amplifies the inflammatory response and aggravates diabetic vascular complications. These pro-inflammatory cytokines stimulate the expression and release of pro-coagulant molecules and inhibit the expression of anti-coagulant molecules by endothelial cells [ 245]. This leads to a pro-coagulant state in the surface of the endothelium and increases growth factor production resulting in a thickening of the basement membrane, thus favoring protein and lipid deposition and impairing vasodilation [ 242, 246].

6.2.2. Endothelial Dysfunction in T2DM and Atherosclerosis Development

6.3. Diabetes-Associated Chronic Inflammation and Atherosclerosis Progression

A critical component of T2DM is a chronic low-grade inflammatory state, referred to as "metaflammation" [ 250]. This chronic condition involves the same cellular and molecular players of acute inflammatory responses and has been suggested as an underlying cause of the progression of atherosclerosis in T2DM. Hyperglycaemia can increase circulating cytokines that can lead to chronic inflammation in T2DM [ 250]. Among them, patients with T2DM have higher levels of IL-1b, IL-6, IL-8, MCP-1, and other major cytokines in both monocytes and macrophages [ 130]. The underlying mechanisms involved in this process are ROS-mediated activation of p38 and other proinflammatory kinases, upregulation of NF-kB induction, oxidative stress, and activation of the AGE-RAGE pathway [ 129, 130]. In addition, exposure to high glucose levels impairs the phagocytic activity of macrophages, which partially explains the increased incidence of chronic infection among T2DM patients [ 251]. Indeed, T2DM is associated with increased activity of the inflammasome, upregulation of the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3), increased levels of IL-1β and IL-18 [ 252, 253, 254]. These events trigger neutrophil extracellular trap activation, or NETosis, a characteristic cell death of macrophages causing chronic inflammation [ 255]. High levels of these markers have been found in T2DM patients [ 256], which are enhanced in hyperglycaemic conditions [ 257].

6.4. Adipokine Balance and CVD Risk

Adipose tissue dysfunction as a result of T2DM can result in an imbalance between pro-inflammatory and anti-inflammatory adipokines, and is one of the mechanisms of T2DM complications. Several studies indicate that adipokines are related to IR, and can result in endothelial dysfunction, and pro-inflammatory and pro-atherogenic states [ 258, 259].

Adiponectin is a well-described insulin-sensitizing hormone and its expression and circulating levels are inversely proportional to the extent of adiposity. Adiponectin has insulin-sensitizing properties [ 260, 261]. Adiponectin acts through ADIPOR1 and ADIPOR2 receptors [ 262] and the peroxisome proliferator-activated receptor α (PPARα) pathway, leading to decreased hepatic gluconeogenesis, increased liver and skeletal muscle fatty acid oxidation, increased glucose uptake in skeletal muscle and white adipose tissue, and decreased white adipose tissue inflammation [ 263]. In addition, adiponectin ameliorates β-cell death by neutralizing inflammatory and lipotoxic ceramides and DAGs [ 264] and shows strong anti-inflammatory effects on other cell types such as macrophages and fibrogenic cells [ 263, 265, 266]. Low concentrations of adiponectin have been found in T2DM patients and are correlated with increased risk of developing premature arteriosclerosis, and are thus considered an additional CVD risk factor [ 267]. Notably, adiponectin deficiency is associated with coronary artery disease, hypertension, endothelial dysfunction and greater carotid intima-media thickness [ 268, 269, 270, 271]. Low concentrations of adiponectin lead to an increased expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, promotes differentiation of macrophages into foam cells and enhances the proliferation and migration of smooth muscle cells [ 272].

Omentin is an adipokine secreted from white adipose tissue and is involved in glucose homeostasis [ 273, 274]. Omentin circulates in the blood [ 275, 276], and is associated with reduced levels in T2DM patients [ 277, 278]. In vitro studies have shown that omentin enhances insulin-stimulated glucose uptake in human adipocytes by AKT signaling pathway activation [ 273]. In humans, an inverse correlation between omentin levels and IR is seen, both at the protein and mRNA levels [ 277, 279, 280]. Additional studies show that omentin has anti-inflammatory properties, diminishes cytokine expression [ 281, 282], and is negatively associated with systemic inflammatory markers such as TNF and IL-6 [ 283].

Vaspin (visceral adipose tissue-derived serine protease inhibitor) is an adipokine that inhibits proteases responsible for IR and protects against atherosclerosis and plaque development [ 284, 285]. It has been shown that T2DM patients have higher serum vaspin levels than healthy controls. Higher vaspin levels are associated with a 1.7-fold increased risk of CVD [ 70]. High vaspin is also associated with increased severity of coronary artery disease [ 286].

7. Conclusions

The importance of research in the fields of glucose homeostasis, insulin and diabetes has not faded. In fact, due to rapid globalization and the normalization of a sedentary lifestyle, along with increased obesity, diabetes and their consequent co-morbidities, research in this topic must continue to grow. Understanding the mechanisms implicated in every step in the development and complications of T2DM is crucial in order to prevent, control, treat or revert the pathophysiology of T2DM its complications. Although quality outcomes for patients are optimized by early detection of T2DM through screening and intensive patient-centered management, research efforts are needed to define causative factors accounting for correlations among different demographic subsets and the corresponding variable risks for T2DM as well as the drivers of increased risk in individuals of low socioeconomic status. Being the pathophysiology and underlying mechanisms of T2DM increasingly understood, precision medicine should be implemented and treatments individualized and targeted appropriately with the help of molecular genetic tools by identifying specific variants contributing to disease development as well as by searching biomarkers to assess progression and response to therapeutic interventions. Additional research is needed to determine a direct causal role of the intestinal microbiota in pathogenesis of T2DM and response to therapies needs to be determined.

Taking everything in this review into consideration, it is clear that there is still a long way until we fully understand each of the many stakeholders in glucose homeostasis.

Author Contributions

U.G.-C., A.B.-V., S.J., A.L.-S., H.S., K.B.U., H.O. and C.M. have contributed to the writing of the manuscript. U.G.-G. and C.M. conceptualized the review. A.B.-V. and C.M. drawn the images. H.S. edited language. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the Basque Government (Grupos Consolidados IT-1264-19). U.G-G. was supported by Fundación Biofísica Bizkaia. A.B.-V. was supported by Programa de especializaci.n de Personal Investigador Doctor en la UPV/EHU (2019) 2019-2020. S.J. and A.L-S. were supported by a grant PIF (2017-2018) and (2019-2020), Gobierno Vasco, respectively. A.L.-S. was partially supported by Fundación Biofísica Bizkaia.

Conflicts of Interest

The authors declare no conflict of interest.

References

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Figure 1. Signaling pathways involved in insulin secretion in β-cells in physiological conditions ( A) and mechanisms leading to dysfunction ( B). ( A) Insulin release is primarily triggered by a response to high glucose concentrations and glucose in mainly internalized mainly through GLUT2 transporter. Glucose catabolism increases ATP/ADP ratio, ATP-dependant potassium channels are closed leading to membrane depolarization and opening of the voltage dependant Ca ²⁺ channels. The latter enables Ca ²⁺ influx triggering insulin exocytosis. Additional Ca ²⁺ channels as P2X, P2Y, SERCA and RYR contribute to Ca ²⁺ mobilization and insulin secretion. ( B) hyperglycemia and hyperlipidemia promote oxidative stress leading to ROS generation that inhibits Ca ²⁺ mobilization and activates proapoptotic signals. Additionally, an excess of FFAs and hyperglycemia lead to the activation of the apoptotic unfolded protein response (UPR) pathways and generation of ER stress. Sustained high glucose levels increase proinsulin and IAAP biosynthesis, which generate ROS. GLUT2: glucose transporter 2, P2X: purinergic receptor X; P2Y: purinergic receptor Y; IP2: inositol 1,3-bisphosphate; IP3: inositol 1,4,5-trisphosphate; RYR: ryanodine receptor channel; SERCA: sarco-endoplasmic reticulum Ca ²⁺-ATPase; FFA: free fatty acid, ROS: reactive oxygen species; UPR: unfolded protein response.

Figure 3. Mitochondrial dysfunction and contribution to T2DM development. Oxidative stress, defective mitochondrial biogenesis and impaired mitophagy promote mitochondrial dysfunction. Generation of ROS links mitochondrial dysfunction and IR. As a consequence of nutrient overload, electron supply to the mitochondrial ETC increases and the electron excess is transferred to oxygen generating O ₂− and H ₂O ₂. ROS oxidize proteins, damage DNA and membrane lipids. Mitofusin-2 and PGC 1α are downregulated leading to reduced mitochondrial biogenesis. Cellular stress and ROS production contribute to higher mitochondrial fission and impaired mitophagy. PCG 1α: Peroxisome proliferator-activated receptor-gamma coactivator-1.

Figure 7. Diabetic dyslipidemia: mechanisms leading to T2DM dyslipidemia and lipoprotein clearance in physiological an IR conditions. ( A) IR leads to an impaired adipose tissue fat storage, resulting in constitutive FFA release from the intracellular TG stores of adipocytes. The released FFAs are taken up by hepatocytes, where they can be directed to the mitochondria and undergo β-oxidation; be re-assimilated into TG to assemble new VLDL particles; shifted to gluconeogenesis resulting in a worsening of hyperglycemia; or stored as TG leading to hepatic steatosis. ( B) Under physiological conditions, VLDL particles incorporate apo-CII and apoE from HDL allowing VLDL to be progressively lipolyzed leading to the generation of smaller VLDL particles (upper panel). T2DM and IR impair metabolism and clearance of chylomicrons and VLDLs. Activation of CETP promotes an exchange of TG out of RLPs and incorporates CE from HDL and LDL particles leading to reduced levels of circulating HDL-C and an increase in the more atherogenic sdLDL particles (lower panel). TG: triglyceride; FFA: free fatty acid, LPL: lipoprotein Lipase; CR: chylomicron remnants; HL: hepatic lipase; CETP: Cholesteryl Ester Transfer Protein; ApoE: apolopoprotein E; ApoC-II: apolipoprotein CII; apoC-III: apolipoprotein CIII; VLDL: very low-density lipoprotein; sdLDL: small dense lipoprotein.

Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, Ostolaza H, Martín C. Pathophysiology of Type 2 Diabetes Mellitus. International Journal of Molecular Sciences. 2020; 21(17):6275. https://doi.org/10.3390/ijms21176275

Chicago/Turabian Style

Galicia-Garcia, Unai, Asier Benito-Vicente, Shifa Jebari, Asier Larrea-Sebal, Haziq Siddiqi, Kepa B. Uribe, Helena Ostolaza, and César Martín. 2020. "Pathophysiology of Type 2 Diabetes Mellitus" International Journal of Molecular Sciences 21, no. 17: 6275. https://doi.org/10.3390/ijms21176275

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Pathophysiology of Type 2 Diabetes Mellitus

# data[].attributes.attachment_link.description
Type 2 Diabetes Mellitus (T2DM), one of the most common metabolic disorders, is caused by a combination of two primary factors: defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin.

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High blood sugar can affect the small blood vessels in the eyes, potentially leading to blurred or distorted vision.

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High blood sugar levels can cause the kidneys to work harder to remove excess sugar, leading to increased urination and dehydration, which in turn triggers thirst.

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Increased thirst caused by type 2 diabetes

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This article is explains the treatment for diabetic thirst.

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What Is Diabetic Thirst and How Can You Fix It?

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Excessive thirst and a dry mouth are telltale signs of high blood sugar. Learn more about diabetic thirst (polydipsia). Causes, symptoms, & what you can do.

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Kidney Disease:

High blood sugar can damage the small blood vessels in the kidneys, leading to diabetic nephropathy.

This damage can impair the kidneys' ability to filter waste products from the blood, potentially leading to chronic kidney disease and, in severe cases, kidney failure.

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Having too much sugar in your blood can cause damage to the retina. People with diabetic retinopathy can lead to diabetic macular edema and neovascular glaucoma both cause increased vision loss.

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Anyone with any kind of diabetes can get diabetic retinopathy - including people with type 1, type 2, and gestational diabetes (a type of diabetes that can develop during pregnancy).

Your risk increases the longer you have diabetes. Over time, more than half of people with diabetes will develop diabetic retinopathy. The good news is that you can lower your risk of developing diabetic retinopathy by controlling your diabetes.

Women with diabetes who become pregnant - or women who develop gestational diabetes - are at high risk for getting diabetic retinopathy. If you have diabetes and are pregnant, have a comprehensive dilated eye exam as soon as possible. Ask your doctor if you'll need additional eye exams during your pregnancy.

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Diabetic retinopathy is an eye condition that can cause vision loss and blindness in people who have diabetes. It affects blood vessels in the retina.

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overtime affected nerves will become damaged and cause four types of neuropathic issues including peripheral sensorimotor, autonomic, proximal, and mononeuropathy.

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Diabetic neuropathy is a type of nerve damage that can occur if you have diabetes. High blood sugar (glucose) can injure nerves throughout the body. Diabetic neuropathy most often damages nerves in the legs and feet.

Depending on the affected nerves, diabetic neuropathy symptoms include pain and numbness in the legs, feet and hands. It can also cause problems with the digestive system, urinary tract, blood vessels and heart. Some people have mild symptoms. But for others, diabetic neuropathy can be quite painful and disabling.

Diabetic neuropathy is a serious diabetes complication that may affect as many as 50% of people with diabetes. But you can often prevent diabetic neuropathy or slow its progress with consistent blood sugar management and a healthy lifestyle.

There are four main types of diabetic neuropathy. You can have one type or more than one type of neuropathy.

Your symptoms depend on the type you have and which nerves are affected. Usually, symptoms develop gradually. You may not notice anything is wrong until considerable nerve damage has occurred.

Peripheral neuropathy

This type of neuropathy may also be called distal symmetric peripheral neuropathy. It's the most common type of diabetic neuropathy. It affects the feet and legs first, followed by the hands and arms. Signs and symptoms of peripheral neuropathy are often worse at night, and may include:

Numbness or reduced ability to feel pain or temperature changes

Tingling or burning feeling

Sharp pains or cramps

Muscle weakness

Extreme sensitivity to touch - for some people, even a bedsheet's weight can be painful

Serious foot problems, such as ulcers, infections, and bone and joint damage

Autonomic neuropathy

The autonomic nervous system controls blood pressure, heart rate, sweating, eyes, bladder, digestive system and sex organs. Diabetes can affect nerves in any of these areas, possibly causing signs and symptoms including:

A lack of awareness that blood sugar levels are low (hypoglycemia unawareness)

Drops in blood pressure when rising from sitting or lying down that may cause dizziness or fainting (orthostatic hypotension)

Bladder or bowel problems

Slow stomach emptying (gastroparesis), causing nausea, vomiting, sensation of fullness and loss of appetite

Difficulty swallowing

Changes in the way the eyes adjust from light to dark or far to near

Increased or decreased sweating

Problems with sexual response, such as vaginal dryness in women and erectile dysfunction in men

Proximal neuropathy (diabetic polyradiculopathy)

This type of neuropathy often affects nerves in the thighs, hips, buttocks or legs. It can also affect the abdominal and chest area. Symptoms are usually on one side of the body, but may spread to the other side. Proximal neuropathy may include:

Severe pain in the buttock, hip or thigh

Weak and shrinking thigh muscles

Difficulty rising from a sitting position

Chest or abdominal wall pain

Mononeuropathy (focal neuropathy)

Mononeuropathy refers to damage to a single, specific nerve. The nerve may be in the face, torso, arm or leg. Mononeuropathy may lead to:

Difficulty focusing or double vision

Paralysis on one side of the face

Numbness or tingling in the hand or fingers

Weakness in the hand that may result in dropping things

Pain in the shin or foot

Weakness causing difficulty lifting the front part of the foot (foot drop)

Pain in the front of the thigh

Call your health care provider for an appointment if you have:

A cut or sore on your foot that is infected or won't heal

Burning, tingling, weakness or pain in your hands or feet that interferes with daily activities or sleep

Changes in digestion, urination or sexual function

Dizziness and fainting

The American Diabetes Association (ADA) recommends that screening for diabetic neuropathy begin immediately after someone is diagnosed with type 2 diabetes or five years after diagnosis with type 1 diabetes. After that, screening is recommended once a year.

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The exact cause of each type of neuropathy is unknown. Researchers think that over time, uncontrolled high blood sugar damages nerves and interferes with their ability to send signals, leading to diabetic neuropathy. High blood sugar also weakens the walls of the small blood vessels (capillaries) that supply the nerves with oxygen and nutrients.

Anyone who has diabetes can develop neuropathy. But these risk factors make nerve damage more likely:

Poor blood sugar control. Uncontrolled blood sugar increases the risk of every diabetes complication, including nerve damage.

Diabetes history. The risk of diabetic neuropathy increases the longer a person has diabetes, especially if blood sugar isn't well controlled.

Kidney disease. Diabetes can damage the kidneys. Kidney damage sends toxins into the blood, which can lead to nerve damage.

Being overweight. Having a body mass index (BMI) of 25 or more may increase the risk of diabetic neuropathy.

Smoking. Smoking narrows and hardens the arteries, reducing blood flow to the legs and feet. This makes it more difficult for wounds to heal and damages the peripheral nerves.

Diabetic neuropathy can cause a number of serious complications, including:

Hypoglycemia unawareness. Blood sugar levels below 70 milligrams per deciliter (mg/dL) - 3.9 millimoles per liter (mmol/L) - usually cause shakiness, sweating and a fast heartbeat. But people who have autonomic neuropathy may not experience these warning signs.

Loss of a toe, foot or leg. Nerve damage can cause a loss of feeling in the feet, so even minor cuts can turn into sores or ulcers without being noticed. In severe cases, an infection can spread to the bone or lead to tissue death. Removal (amputation) of a toe, foot or even part of the leg may be necessary.

Urinary tract infections and urinary incontinence. If the nerves that control the bladder are damaged, the bladder may not empty completely when urinating. Bacteria can build up in the bladder and kidneys, causing urinary tract infections. Nerve damage can also affect the ability to feel the need to urinate or to control the muscles that release urine, leading to leakage (incontinence).

Sharp drops in blood pressure. Damage to the nerves that control blood flow can affect the body's ability to adjust blood pressure. This can cause a sharp drop in pressure when standing after sitting or lying down, which may lead to lightheadedness and fainting.

Digestive problems. If nerve damage occurs in the digestive tract, constipation or diarrhea, or both are possible. Diabetes-related nerve damage can lead to gastroparesis, a condition in which the stomach empties too slowly or not at all. This can cause bloating and indigestion.

Sexual dysfunction. Autonomic neuropathy often damages the nerves that affect the sex organs. Men may experience erectile dysfunction. Women may have difficulty with lubrication and arousal.

Increased or decreased sweating. Nerve damage can disrupt how the sweat glands work and make it difficult for the body to control its temperature properly.

You can prevent or delay diabetic neuropathy and its complications by closely managing your blood sugar and taking good care of your feet.

Blood sugar management

The American Diabetes Association (ADA) recommends that people living with diabetes have a glycated hemoglobin (A1C) test at least twice a year. This test indicates your average blood sugar level for the past 2 to 3 months.

glycated hemoglobin (A1C) goals may need to be individualized, but for many adults, the ADA recommends an A1C of less than 7.0%. If your blood sugar levels are higher than your goal, you may need changes in your daily management, such as adding or adjusting your medications or changing your diet or physical activity.

Foot care

Foot problems, including sores that don't heal, ulcers and even amputation, are common complications of diabetic neuropathy. But you can prevent many of these problems by having a thorough foot exam at least once a year. Also have your health care provider check your feet at each office visit and take good care of your feet at home.

Follow your health care provider's recommendations for good foot care. To protect the health of your feet:

Check your feet every day. Look for blisters, cuts, bruises, cracked and peeling skin, redness, and swelling. Use a mirror or ask a friend or family member to help examine parts of your feet that are hard to see.

Keep your feet clean and dry. Wash your feet every day with lukewarm water and mild soap. Don't soak your feet. Dry your feet and between your toes thoroughly.

Moisturize your feet. This helps prevent cracking. But don't get lotion between your toes because it might encourage fungal growth.

Trim your toenails carefully. Cut your toenails straight across. File the edges carefully so that you have smooth edges. If you can't do this yourself, a specialist in foot problems (podiatrist) can help.

Wear clean, dry socks. Look for socks made of cotton or moisture-wicking fibers that don't have tight bands or thick seams.

Wear cushioned shoes that fit well. Wear closed-toed shoes or slippers to protect your feet. Make sure your shoes fit properly and allow your toes to move. A foot specialist can teach you how to buy properly fitted shoes and to prevent problems such as corns and calluses. If you qualify for Medicare, your plan may cover the cost of at least one pair of shoes each year.

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8. Baute V, et al. Complementary and alternative medicine for painful peripheral neuropathy. Current Treatment Options in Neurology. 2019; doi:10.1007/s11940-019-0584-z.

9. Feldman EL, et al. Diabetic neuropathy. Nature Reviews - Disease Primers. 2019; doi:10.1038/s41572-019-0092-1.

10. Cutsforth-Gregory (expert opinion). Mayo Clinic. Dec. 24, 2021.

11. Castro MR (expert opinion). Mayo Clinic. Jan. 21, 2022.

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An often preventable complication of diabetes-Diabetic neuropathy - Symptoms & causes - Mayo Clinic

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High blood sugar can lead to nerve damage in feet and other areas of the body. Know the signs and how to take steps to prevent this diabetes complication.

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People with diabetes are more likely to develop heart disease at a younger age and the risk of stroke doubles compared to the average adult without diabetes.

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National Institute of Diabetes and Digestive and Kidney Diseases

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Having diabetes means that you are more likely to develop heart disease and have a greater chance of a heart attack or a stroke. People with diabetes are also more likely to have certain conditions, or risk factors, that increase the chances of having heart disease or stroke, such as high blood pressure or high cholesterol. If you have diabetes, you can protect your heart and health by managing your blood glucose, also called blood sugar, as well as your blood pressure and cholesterol. If you smoke, get help to stop.

Over time, high blood glucose from diabetes can damage your blood vessels and the nerves that control your heart and blood vessels. The longer you have diabetes, the higher the chances that you will develop heart disease. ¹

People with diabetes tend to develop heart disease at a younger age than people without diabetes. In adults with diabetes, the most common causes of death are heart disease and stroke. Adults with diabetes are nearly twice as likely to die from heart disease or stroke as people without diabetes. ²

The good news is that the steps you take to manage your diabetes also help to lower your chances of having heart disease or stroke.

What else increases my chances of heart disease or stroke if I have diabetes?

If you have diabetes, other factors add to your chances of developing heart disease or having a stroke.

Smoking

Smoking raises your risk of developing heart disease. If you have diabetes, it is important to stop smoking because both smoking and diabetes narrow blood vessels. Smoking also increases your chances of developing other long-term problems such as lung disease. Smoking also can damage the blood vessels in your legs and increase the risk of lower leg infections, ulcers, and amputation.

High blood pressure

If you have high blood pressure, your heart must work harder to pump blood. High blood pressure can strain your heart, damage blood vessels, and increase your risk of heart attack, stroke, eye problems, and kidney problems.

Abnormal cholesterol levels

Cholesterol is a type of fat produced by your liver and found in your blood. You have two kinds of cholesterol in your blood: LDL and HDL.

LDL, often called "bad" cholesterol, can build up and clog your blood vessels. High levels of LDL cholesterol raise your risk of developing heart disease.

Another type of blood fat, triglycerides, also can raise your risk of heart disease when the levels are higher than recommended by your health care team.

Obesity and belly fat

Being overweight or obese can affect your ability to manage your diabetes and increase your risk for many health problems, including heart disease and high blood pressure. If you are overweight, a healthy eating plan with reduced calories often will lower your glucose levels and reduce your need for medications.

Excess belly fat around your waist, even if you are not overweight, can raise your chances of developing heart disease.

Even if you are a normal weight, excess belly fat can raise your risk for heart disease.

You have excess belly fat if your waist measures

more than 40 inches and you are a man

more than 35 inches and you are a woman

Learn how to correctly measure your waist.
Family history of heart disease

A family history of heart disease may also add to your chances of developing heart disease. If one or more of your family members had a heart attack before age 50, you may have an even higher chance of developing heart disease. ³

You can't change whether heart disease runs in your family, but if you have diabetes, it's even more important to take steps to protect yourself from heart disease and decrease your chances of having a stroke.

How can I lower my chances of a heart attack or stroke if I have diabetes?

Taking care of your diabetes is important to help you take care of your heart. You can lower your chances of having a heart attack or stroke by taking the following steps to manage your diabetes to keep your heart and blood vessels healthy.

Manage your diabetes ABCs

Knowing your diabetes ABCs will help you manage your blood glucose, blood pressure, and cholesterol. Stopping smoking if you have diabetes is also important to lower your chances for heart disease.

A is for the A1C test. The A1C test shows your average blood glucose level over the past 3 months. This is different from the blood glucose checks that you do every day. The higher your A1C number, the higher your blood glucose levels have been during the past 3 months. High levels of blood glucose can harm your heart, blood vessels, kidneys, feet, and eyes.

The A1C goal for many people with diabetes is below 7 percent. Some people may do better with a slightly higher A1C goal. Ask your health care team what your goal should be.

B is for blood pressure. Blood pressure is the force of your blood against the wall of your blood vessels. If your blood pressure gets too high, it makes your heart work too hard. High blood pressure can cause a heart attack or stroke and damage your kidneys and eyes.

The blood pressure goal for most people with diabetes is below 140/90 mm Hg. Ask what your goal should be.

C is for cholesterol. You have two kinds of cholesterol in your blood: LDL and HDL. LDL or "bad" cholesterol can build up and clog your blood vessels. Too much bad cholesterol can cause a heart attack or stroke. HDL or "good" cholesterol helps remove the "bad" cholesterol from your blood vessels.

Ask your health care team what your cholesterol numbers should be. If you are over 40 years of age, you may need to take medicine such as a statin to lower your cholesterol and protect your heart. Some people with very high LDL ("bad") cholesterol may need to take medicine at a younger age.

S is for stop smoking. Not smoking is especially important for people with diabetes because both smoking and diabetes narrow blood vessels, so your heart has to work harder.

If you quit smoking

you will lower your risk for heart attack, stroke, nerve disease, kidney disease, eye disease, and amputation

your blood glucose, blood pressure, and cholesterol levels may improve

your blood circulation will improve

you may have an easier time being physically active

If you smoke or use other tobacco products, stop. Ask for help so you don't have to do it alone. You can start by calling the national quitline at 1-800-QUITNOW or 1-800-784-8669. For tips on quitting, go to Smokefree.gov.

Ask your health care team about your goals for A1C, blood pressure, and cholesterol, and what you can do to reach these goals.

Develop or maintain healthy lifestyle habits

Developing or maintaining healthy lifestyle habits can help you manage your diabetes and prevent heart disease.

Follow your healthy eating plan.

Make physical activity part of your routine.

Stay at or get to a healthy weight

Get enough sleep.

Learn more about these tips to manage diabetes.

Develop or maintain healthy lifestyle habits. Physical activity can help you manage your diabetes and may help you cope with stress.

Watch a video about what you can do to keep your heart healthy.
Learn to manage stress

Managing diabetes is not always easy. Feeling stressed, sad, or angry is common when you are living with diabetes. You may know what to do to stay healthy but may have trouble sticking with your plan over time. Long-term stress can raise your blood glucose and blood pressure, but you can learn ways to lower your stress. Try deep breathing, gardening, taking a walk, doing yoga, meditating, doing a hobby, or listening to your favorite music. Learn more about healthy ways to cope with stress.

Take medicine to protect your heart

Medicines may be an important part of your treatment plan. Your doctor will prescribe medicine based on your specific needs. Medicine may help you

meet your A1C (blood glucose), blood pressure, and cholesterol goals.

reduce your risk of blood clots, heart attack, or stroke.

treat angina, or chest pain that is often a symptom of heart disease. (Angina can also be an early symptom of a heart attack.)

Ask your doctor whether you should take aspirin. Aspirin is not safe for everyone. Your doctor can tell you whether taking aspirin is right for you and exactly how much to take.

Statins can reduce the risk of having a heart attack or stroke in some people with diabetes. Statins are a type of medicine often used to help people meet their cholesterol goals. Talk with your doctor to find out whether taking a statin is right for you.

Talk with your doctor if you have questions about your medicines. Before you start a new medicine, ask your doctor about possible side effects and how you can avoid them. If the side effects of your medicine bother you, tell your doctor. Don't stop taking your medicines without checking with your doctor first.

Take medicines as prescribed.

How do doctors diagnose heart disease in diabetes?

Doctors diagnose heart disease in diabetes based on

your symptoms

your medical and family history

how likely you are to have heart disease

a physical exam

results from tests and procedures

Tests used to monitor your diabetes-A1C, blood pressure, and cholesterol-help your doctor decide whether it is important to do other tests to check your heart health.

Your health care provider will do a physical exam.

What are the warning signs of heart attack and stroke?

Call 9-1-1 right away if you have warning signs of a heart attack:

pain or pressure in your chest that lasts longer than a few minutes or goes away and comes back

pain or discomfort in one or both of your arms or shoulders; or your back, neck, or jaw

shortness of breath

sweating or light-headedness

indigestion or nausea (feeling sick to your stomach)

feeling very tired

Treatment works best when it is given right away. Warning signs can be different in different people. You may not have all of these symptoms.

If you have angina, it's important to know how and when to seek medical treatment.

Women sometimes have nausea and vomiting, feel very tired (sometimes for days), and have pain in the back, shoulders, or jaw without any chest pain.

People with diabetes-related nerve damage may not notice any chest pain.

Call 9-1-1 right away if you have warning signs of a stroke, including sudden

weakness or numbness of your face, arm, or leg on one side of your body

confusion, or trouble talking or understanding

dizziness, loss of balance, or trouble walking

trouble seeing out of one or both eyes

sudden severe headache

If you have any one of these warning signs, call 9-1-1. You can help prevent permanent damage by getting to a hospital within an hour of a stroke.

Call 9-1-1 if you have the warning signs of a heart attack or stroke. Treatment works best when given right away.

References

[1] Huo X, Gao L, Guo L, et al. Risk of non-fatal cardiovascular diseases in early-onset versus late-onset type 2 diabetes in China: a cross-sectional study. The Lancet Diabetes & Endocrinology. 2016;4(2):115-124.

[2] National Centers for Disease Control and Prevention. National diabetes statistics report, 2014. https://www.cdc.gov/diabetes/data/statistics/statistics-report.html. Accessed December 22, 2016.

[3] Kolber MR, Scrimshaw C. Family history of cardiovascular disease. Canadian Family Physician. 2014;60(11):1016.

Clinical Trials

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and other components of the National Institutes of Health (NIH) conduct and support research into many diseases and conditions.

What are clinical trials, and are they right for you?

Clinical trials are part of clinical research and at the heart of all medical advances. Clinical trials look at new ways to prevent, detect, or treat disease. Researchers also use clinical trials to look at other aspects of care, such as improving the quality of life for people with chronic illnesses. Find out if clinical trials are right for you.

What clinical trials are open?

Clinical trials that are currently open and are recruiting can be viewed at www.ClinicalTrials.gov.

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Diabetes, Heart Disease, and Stroke | NIDDK

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Having diabetes means that you are more likely to develop heart disease and have a greater chance of a heart attack or a stroke. People with diabetes are also more likely to have certain conditions, or risk factors, that increase the chances of having heart disease or stroke, such as high blood pressure or high cholesterol.

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Along with the high blood sugar, one symptom may be weight loss without any change to diet or exercise due to the increased urination and dehydration.

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What Are the Signs and Symptoms of Type 2 Diabetes?

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Early signs and symptoms of type 2 diabetes include thirst, hunger, and excessive urination. But often type 2 diabetes symptoms won’t appear until blood sugar gets high enough. Warning signs may also vary in men versus women. Here’s what to look for.

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Another symptom can be the slow-healing of wounds. This stems from the dehydration and the high blood sugar that doesn't allow your body to recover as quickly.

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The following symptoms of diabetes are typical. However, some people with type 2 diabetes have symptoms so mild that they go unnoticed.

Common symptoms of diabetes:

Urinating often

Feeling very thirsty

Feeling very hungry-even though you are eating

Extreme fatigue

Blurry vision

Cuts/bruises that are slow to heal

Tingling, pain, or numbness in the hands/feet (type 2)

Early detection and treatment of diabetes can decrease the risk of developing the complications of diabetes.

Although there are many similarities between type 1 and type 2 diabetes, the cause of each is very different. And the treatment is usually quite different, too. Some people, especially adults who are newly diagnosed with type 1 diabetes, may have symptoms similar to type 2 diabetes and this overlap between types can be confusing. Take our Risk Test to find out if you are at increased risk for having type 2 diabetes.

Maybe it's a different type

If you or someone you know is diagnosed with type 2 diabetes but isn't responding well to the typical treatments for type 2 diabetes, it may be worth a visit to an endocrinologist to determine what type of diabetes is happening. Generally, this requires antibody tests and possibly the measurement of a C-peptide level.

Gestational diabetes

Women with gestational diabetes often have no symptoms, which is why it's important for at-risk women to be tested at the proper time during pregnancy.

Symptoms of diabetes complications

Have you already been diagnosed with diabetes but are concerned about symptoms that may be the result of complications related to diabetes?
Find out more

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Read to understand type 2 diabetes symptoms, similarities between type 1 and type 2 diabetes. Take our 60- second type 2 risk test.

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Exercising more and eating healthier can help lead to better control of your body's blood sugar levels which can, overall, help with your Type 2.

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NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

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Learn about the symptoms of type 2 diabetes, what causes the disease, how it’s diagnosed, and steps you can take to help prevent or delay type 2 diabetes.

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One method of diagnosing Type 2 Diabetes is using a Fasting Plasma Glucose test. This has you fast overnight and then they test your blood sugar levels to see if there are abnormalities.

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Type 2 Diabetes| Adult-Onset Diabetes | MedlinePlus

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Type 2 Diabetes, previously referred to as Adult Onset Diabetes, is the more common type. Risk factors include obesity and family history.

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Another way to diagnose Type 2 is through an oral glucose tolerance test which consists of drinking a sugary drink and monitoring your blood glucose levels over the course of 2 hours. It is mainly used with pregnant women and people with cystic fibrosis.

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Diagnosis

Type 2 diabetes is usually diagnosed using the glycated hemoglobin (A1C) test. This blood test indicates your average blood sugar level for the past two to three months. Results are interpreted as follows:

Below 5.7% is normal.

5.7% to 6.4% is diagnosed as prediabetes.

6.5% or higher on two separate tests indicates diabetes.

If the A1C test isn't available, or if you have certain conditions that interfere with an A1C test, your health care provider may use the following tests to diagnose diabetes:

Random blood sugar test. Blood sugar values are expressed in milligrams of sugar per deciliter ( mg/dL) or millimoles of sugar per liter ( mmol/L) of blood. Regardless of when you last ate, a level of 200 mg/dL (11.1 mmol/L) or higher suggests diabetes, especially if you also have symptoms of diabetes, such as frequent urination and extreme thirst.

Fasting blood sugar test. A blood sample is taken after you haven't eaten overnight. Results are interpreted as follows:

Less than 100 mg/dL (5.6 mmol/L) is considered healthy.

100 to 125 mg/dL (5.6 to 6.9 mmol/L) is diagnosed as prediabetes.

126 mg/dL (7 mmol/L) or higher on two separate tests is diagnosed as diabetes.

Oral glucose tolerance test. This test is less commonly used than the others, except during pregnancy. You'll need to not eat for a certain amount of time and then drink a sugary liquid at your health care provider's office. Blood sugar levels then are tested periodically for two hours. Results are interpreted as follows:

Less than 140 mg/dL (7.8 mmol/L) after two hours is considered healthy.

140 to 199 mg/dL (7.8 mmol/L and 11.0 mmol/L) is diagnosed as prediabetes.

200 mg/dL (11.1 mmol/L) or higher after two hours suggests diabetes.

Screening. The American Diabetes Association recommends routine screening with diagnostic tests for type 2 diabetes in all adults age 35 or older and in the following groups:

After a diagnosis

If you're diagnosed with diabetes, your health care provider may do other tests to distinguish between type 1 and type 2 diabetes because the two conditions often require different treatments.

Your health care provider will test A1C levels at least two times a year and when there are any changes in treatment. Target A1C goals vary depending on age and other factors. For most people, the American Diabetes Association recommends an A1C level below 7%.

You also receive tests to screen for complications of diabetes and other medical conditions.

Treatment

Management of type 2 diabetes includes:

Healthy eating.

Regular exercise.

Weight loss.

Possibly, diabetes medication or insulin therapy.

Blood sugar monitoring.

These steps make it more likely that blood sugar will stay in a healthy range. And they may help to delay or prevent complications.

Healthy eating

There's no specific diabetes diet. However, it's important to center your diet around:

A regular schedule for meals and healthy snacks.

Smaller portion sizes.

More high-fiber foods, such as fruits, nonstarchy vegetables and whole grains.

Fewer refined grains, starchy vegetables and sweets.

Modest servings of low-fat dairy, low-fat meats and fish.

Healthy cooking oils, such as olive oil or canola oil.

Fewer calories.

Your health care provider may recommend seeing a registered dietitian, who can help you:

Physical activity

Exercise is important for losing weight or maintaining a healthy weight. It also helps with managing blood sugar. Talk to your health care provider before starting or changing your exercise program to ensure that activities are safe for you.

Aerobic exercise. Choose an aerobic exercise that you enjoy, such as walking, swimming, biking or running. Adults should aim for 30 minutes or more of moderate aerobic exercise on most days of the week, or at least 150 minutes a week.

Resistance exercise. Resistance exercise increases your strength, balance and ability to perform activities of daily living more easily. Resistance training includes weightlifting, yoga and calisthenics. Adults living with type 2 diabetes should aim for 2 to 3 sessions of resistance exercise each week.

Limit inactivity. Breaking up long periods of inactivity, such as sitting at the computer, can help control blood sugar levels. Take a few minutes to stand, walk around or do some light activity every 30 minutes.

Weight loss

Weight loss results in better control of blood sugar levels, cholesterol, triglycerides and blood pressure. If you're overweight, you may begin to see improvements in these factors after losing as little as 5% of your body weight. However, the more weight you lose, the greater the benefit to your health. In some cases, losing up to 15% of body weight may be recommended.

Your health care provider or dietitian can help you set appropriate weight-loss goals and encourage lifestyle changes to help you achieve them.

Monitoring your blood sugar

Your health care provider will advise you on how often to check your blood sugar level to make sure you remain within your target range. You may, for example, need to check it once a day and before or after exercise. If you take insulin, you may need to check your blood sugar multiple times a day.

Monitoring is usually done with a small, at-home device called a blood glucose meter, which measures the amount of sugar in a drop of blood. Keep a record of your measurements to share with your health care team.

Continuous glucose monitoring is an electronic system that records glucose levels every few minutes from a sensor placed under the skin. Information can be transmitted to a mobile device such as a phone, and the system can send alerts when levels are too high or too low.

Diabetes medications

If you can't maintain your target blood sugar level with diet and exercise, your health care provider may prescribe diabetes medications that help lower glucose levels, or your provider may suggest insulin therapy. Medicines for type 2 diabetes include the following.

Metformin (Fortamet, Glumetza, others) is generally the first medicine prescribed for type 2 diabetes. It works mainly by lowering glucose production in the liver and improving the body's sensitivity to insulin so it uses insulin more effectively.

Some people experience B-12 deficiency and may need to take supplements. Other possible side effects, which may improve over time, include:

Sulfonylureas help the body secrete more insulin. Examples include glyburide (DiaBeta, Glynase), glipizide (Glucotrol XL) and glimepiride (Amaryl). Possible side effects include:

Glinides stimulate the pancreas to secrete more insulin. They're faster acting than sulfonylureas. But their effect in the body is shorter. Examples include repaglinide and nateglinide. Possible side effects include:

Thiazolidinediones make the body's tissues more sensitive to insulin. An example of this medicine is pioglitazone (Actos). Possible side effects include:

DPP-4 inhibitors help reduce blood sugar levels but tend to have a very modest effect. Examples include sitagliptin (Januvia), saxagliptin (Onglyza) and linagliptin (Tradjenta). Possible side effects include:

GLP-1 receptor agonists are injectable medications that slow digestion and help lower blood sugar levels. Their use is often associated with weight loss, and some may reduce the risk of heart attack and stroke. Examples include exenatide (Byetta, Bydureon Bcise), liraglutide (Saxenda, Victoza) and semaglutide (Rybelsus, Ozempic, Wegovy). Possible side effects include:

SGLT2 inhibitors affect the blood-filtering functions in the kidneys by blocking the return of glucose to the bloodstream. As a result, glucose is removed in the urine. These medicines may reduce the risk of heart attack and stroke in people with a high risk of those conditions. Examples include canagliflozin (Invokana), dapagliflozin (Farxiga) and empagliflozin (Jardiance). Possible side effects include:

Vaginal yeast infections.

Urinary tract infections.

Low blood pressure.

High cholesterol.

Risk of gangrene.

Risk of bone fractures (canagliflozin).

Risk of amputation (canagliflozin).

Other medicines your health care provider might prescribe in addition to diabetes medications include blood pressure and cholesterol-lowering medicines, as well as low-dose aspirin, to help prevent heart and blood vessel disease.

Insulin therapy

Some people who have type 2 diabetes need insulin therapy. In the past, insulin therapy was used as a last resort, but today it may be prescribed sooner if blood sugar targets aren't met with lifestyle changes and other medicines.

Different types of insulin vary on how quickly they begin to work and how long they have an effect. Long-acting insulin, for example, is designed to work overnight or throughout the day to keep blood sugar levels stable. Short-acting insulin generally is used at mealtime.

Your health care provider will determine what type of insulin is right for you and when you should take it. Your insulin type, dosage and schedule may change depending on how stable your blood sugar levels are. Most types of insulin are taken by injection.

Side effects of insulin include the risk of low blood sugar - a condition called hypoglycemia - diabetic ketoacidosis and high triglycerides.

Weight-loss surgery

Weight-loss surgery changes the shape and function of the digestive system. This surgery may help you lose weight and manage type 2 diabetes and other conditions related to obesity. There are several surgical procedures. All of them help people lose weight by limiting how much food they can eat. Some procedures also limit the amount of nutrients the body can absorb.

Weight-loss surgery is only one part of an overall treatment plan. Treatment also includes diet and nutritional supplement guidelines, exercise and mental health care.

Generally, weight-loss surgery may be an option for adults living with type 2 diabetes who have a body mass index (BMI) of 35 or higher. BMI is a formula that uses weight and height to estimate body fat. Depending on the severity of diabetes or the presence of other medical conditions, surgery may be an option for someone with a BMI lower than 35.

Weight-loss surgery requires a lifelong commitment to lifestyle changes. Long-term side effects may include nutritional deficiencies and osteoporosis.

Pregnancy

People living with type 2 diabetes often need to change their treatment plan during pregnancy and follow a diet that controls carbohydrates. Many people need insulin therapy during pregnancy. They also may need to stop other treatments, such as blood pressure medicines.

There is an increased risk during pregnancy of developing a condition that affects the eyes called diabetic retinopathy. In some cases, this condition may get worse during pregnancy. If you are pregnant, visit an ophthalmologist during each trimester of your pregnancy and one year after you give birth. Or as often as your health care provider suggests.

Signs of trouble

Regularly monitoring your blood sugar levels is important to avoid severe complications. Also, be aware of symptoms that may suggest irregular blood sugar levels and the need for immediate care:

High blood sugar. This condition also is called hyperglycemia. Eating certain foods or too much food, being sick, or not taking medications at the right time can cause high blood sugar. Symptoms include:

Hyperglycemic hyperosmolar nonketotic syndrome (HHNS). This life-threatening condition includes a blood sugar reading higher than 600 mg/dL (33.3 mmol/L). HHNS may be more likely if you have an infection, are not taking medicines as prescribed, or take certain steroids or drugs that cause frequent urination. Symptoms include:

Diabetic ketoacidosis. Diabetic ketoacidosis occurs when a lack of insulin results in the body breaking down fat for fuel rather than sugar. This results in a buildup of acids called ketones in the bloodstream. Triggers of diabetic ketoacidosis include certain illnesses, pregnancy, trauma and medicines - including the diabetes medicines called SGLT2 inhibitors.

The toxicity of the acids made by diabetic ketoacidosis can be life-threatening. In addition to the symptoms of hyperglycemia, such as frequent urination and increased thirst, ketoacidosis may cause:

Nausea.

Vomiting.

Abdominal pain.

Shortness of breath.

Fruity-smelling breath.

Low blood sugar. If your blood sugar level drops below your target range, it's known as low blood sugar. This condition also is called hypoglycemia. Your blood sugar level can drop for many reasons, including skipping a meal, unintentionally taking more medication than usual or being more physically active than usual. Symptoms include:

If you have symptoms of low blood sugar, drink or eat something that will quickly raise your blood sugar level. Examples include fruit juice, glucose tablets, hard candy or another source of sugar. Retest your blood in 15 minutes. If levels are not at your target, eat or drink another source of sugar. Eat a meal after your blood sugar level returns to normal.

If you lose consciousness, you need to be given an emergency injection of glucagon, a hormone that stimulates the release of sugar into the blood.

More Information

Show more related information

Clinical trials

Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this condition.

Lifestyle and home remedies

Careful management of type 2 diabetes can reduce the risk of serious - even life-threatening - complications. Consider these tips:

Commit to managing your diabetes. Learn all you can about type 2 diabetes. Make healthy eating and physical activity part of your daily routine.

Work with your team. Establish a relationship with a certified diabetes education specialist, and ask your diabetes treatment team for help when you need it.

Identify yourself. Wear a necklace or bracelet that says you are living with diabetes, especially if you take insulin or other blood sugar-lowering medicine.

Schedule a yearly physical exam and regular eye exams. Your diabetes checkups aren't meant to replace regular physicals or routine eye exams.

Keep your vaccinations up to date. High blood sugar can weaken your immune system. Get a flu shot every year. Your health care provider also may recommend the pneumonia vaccine. The Centers for Disease Control and Prevention (CDC) also recommends the hepatitis B vaccination if you haven't previously received this vaccine and you're 19 to 59 years old. Talk to your health care provider about other vaccinations you may need.

Take care of your teeth. Diabetes may leave you prone to more-serious gum infections. Brush and floss your teeth regularly and schedule recommended dental exams. Contact your dentist right away if your gums bleed or look red or swollen.

Pay attention to your feet. Wash your feet daily in lukewarm water, dry them gently, especially between the toes, and moisturize them with lotion. Check your feet every day for blisters, cuts, sores, redness and swelling. Contact your health care provider if you have a sore or other foot problem that isn't healing.

Keep your blood pressure and cholesterol under control. Eating healthy foods and exercising regularly can go a long way toward controlling high blood pressure and cholesterol. Take medication as prescribed.

If you smoke or use other types of tobacco, ask your health care provider to help you quit. Smoking increases your risk of diabetes complications. Talk to your health care provider about ways to stop using tobacco.

Use alcohol sparingly. Depending on the type of drink, alcohol may lower or raise blood sugar levels. If you choose to drink alcohol, only do so with a meal. The recommendation is no more than one drink daily for women and no more than two drinks daily for men. Check your blood sugar frequently after drinking alcohol.

Make healthy sleep a priority. Many people with type 2 diabetes have sleep problems. And not getting enough sleep may make it harder to keep blood sugar levels in a healthy range. If you have trouble sleeping, talk to your health care provider about treatment options.

Alternative medicine

Many alternative medicine treatments claim to help people living with diabetes. According to the National Center for Complementary and Integrative Health, studies haven't provided enough evidence to recommend any alternative therapies for blood sugar management. Research has shown the following results about popular supplements for type 2 diabetes:

Chromium supplements have been shown to have few or no benefits. Large doses can result in kidney damage, muscle problems and skin reactions.

Magnesium supplements have shown benefits for blood sugar control in some but not all studies. Side effects include diarrhea and cramping. Very large doses - more than 5,000 mg a day - can be fatal.

Cinnamon, in some studies, has lowered fasting glucose levels but not A1C levels. Therefore, there's no evidence of overall improved glucose management.

Talk to your health care provider before starting a dietary supplement or natural remedy. Do not replace your prescribed diabetes medicines with alternative medicines.

Coping and support

Type 2 diabetes is a serious disease, and following your diabetes treatment plan takes commitment. To effectively manage diabetes, you may need a good support network.

Anxiety and depression are common in people living with diabetes. Talking to a counselor or therapist may help you cope with the lifestyle changes and stress that come with a type 2 diabetes diagnosis.

Support groups can be good sources of diabetes education, emotional support and helpful information, such as how to find local resources or where to find carbohydrate counts for a favorite restaurant. If you're interested, your health care provider may be able to recommend a group in your area.

You can visit the American Diabetes Association website to check out local activities and support groups for people living with type 2 diabetes. The American Diabetes Association also offers online information and online forums where you can chat with others who are living with diabetes. You also can call the organization at 800-DIABETES (800-342-2383).

Preparing for your appointment

At your annual wellness visit, your health care provider can screen for diabetes and monitor and treat conditions that increase your risk of diabetes, such as high blood pressure, high cholesterol or a high BMI.

If you are seeing your health care provider because of symptoms that may be related to diabetes, you can prepare for your appointment by being ready to answer the following questions:

When did your symptoms begin?

Does anything improve the symptoms or worsen the symptoms?

What medicines do you take regularly, including dietary supplements and herbal remedies?

What are your typical daily meals? Do you eat between meals or before bedtime?

How much alcohol do you drink?

How much daily exercise do you get?

Is there a history of diabetes in your family?

If you are diagnosed with diabetes, your health care provider may begin a treatment plan. Or you may be referred to a doctor who specializes in hormonal disorders, called an endocrinologist. Your care team also may include the following specialists:

Talk to your health care provider about referrals to other specialists who may be providing care.

Questions for ongoing appointments

Before any appointment with a member of your treatment team, make sure you know whether there are any restrictions, such as not eating or drinking before taking a test. Questions that you should regularly talk about with your health care provider or other members of the team include:

How often do I need to monitor my blood sugar, and what is my target range?

What changes in my diet would help me better manage my blood sugar?

What is the right dosage for prescribed medications?

When do I take the medications? Do I take them with food?

How does management of diabetes affect treatment for other conditions? How can I better coordinate treatments or care?

When do I need to make a follow-up appointment?

Under what conditions should I call you or seek emergency care?

Are there brochures or online sources you recommend?

Are there resources available if I'm having trouble paying for diabetes supplies?

What to expect from your doctor

Your health care provider is likely to ask you questions at your appointments. Those questions may include:

Do you understand your treatment plan and feel confident you can follow it?

How are you coping with diabetes?

Have you had any low blood sugar?

Do you know what to do if your blood sugar is too low or too high?

What's a typical day's diet like?

Are you exercising? If so, what type of exercise? How often?

Do you sit for long periods of time?

What challenges are you experiencing in managing your diabetes?

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High blood sugar levels are the main problem in diabetes. Learn about lifestyle changes to lower the risk and treatments to manage type 2 diabetes.

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Metformin is a medication that helps improve insulin sensitivity and also reduces the production of glucose by the liver. Its cost can range from $10-30 for generic Metformin, according to GoodRx.com. Most private insurance plans cover Metformin. Without this medication, there are other options but doing nothing, in general, will only allow things to get worse.

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Metformin and ageing: improving ageing outcomes beyond glycaemic control

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In a world where the population is ageing, there is growing interest and demand for research evaluating strategies that address the ageing process. After 60 years of successful use of metformin in our pharmaceutical armamentarium, we are learning…

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Physical therapy can help with Type 2 in many ways. You can suffer from joint problems, weight issues, as well as problems associated with walking. This can be short or long term depending on the severity of your Type 2 and if you can do the exercises on your own or need assistance. Stretching as well as weight training and balance training can all be provided by physical therapists or personal trainers.

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✉Corresponding author: Corresponding author name, Jill
Kanaley, PhD, University of Missouri, 204 Gwynn Hall, Columbia, MO

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Exercise/Physical Activity in Individuals with Type 2 Diabetes: A Consensus Statement from the American College of Sports Medicine - PMC

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This consensus statement is an update of the 2010 ACSM position stand on exercise and type 2 diabetes. Since then, a substantial amount of research on select topics in exercise in individuals of various ages with type 2 diabetes has been published…

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Speech therapy can help with the struggles that may come with Type 2. You can have dysphagia (trouble swallowing), as well as nerve damage. Exercises like tongue exercises or swallowing exercises can help prevent or halt these symptoms. Speech therapists specialize in helping with these issues and performing these exercises.

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Trio Rehabilitation & Wellness Solutions

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How Speech Therapy Helps with Dysphagia? - Trio Rehabilitation & Wellness Solutions

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Speech-Language Pathologists (SLP’s) also known as speech therapists have master’s degrees and are trained rehabilitation therapists with extensive knowledge about the physiological and anatomy of the upper digestive tract for swallowing and speech. Because dysphagia is a complex medical condition, SLP’s work with other professionals,…

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Short acting insulin treatment Novolin R

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Short acting insulin treatment Novolin R

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Novolin R is a short acting insulin treatment. These types of insulins are ideal for use before meals to help bring blood sugar back down to a safe level. This treatment is usually covered by insurance and medicare plans. After insurance a person's copay will usually sit around $50. This is one of many short acting insulins as a readily available and easy to use injection and available over the counter. Main concerns include missing a meal after using Novolin which could cause hypoglycemia.

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Novolin R Regular U-100 Insulin 100 unit/mL injection solution | Kaiser Permanente

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Insulin regular is used with a proper diet and exercise program to control high blood sugar in people with diabetes. Controlling high blood sugar help

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Glargine is a long acting insulin treatment. It is administered by a single injection once per day to maintain optimal glycemic levels, and this can be supported by short acting insulin for better results. This type of medication varies depending on insurance, ranging anywhere from $30 to $150 after insurance is applied. Just like short acting insulin, the main concern for this treatment is hypoglycemia due to overdose of glargine insulin and poor combination with other medications, including beta blockers, clonidine, and guanethidine.

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Continuing Education Activity

Insulin glargine is a synthetic version of human insulin that is FDA-approved to treat adults and children with type 1 diabetes and adults with type 2 diabetes to improve and maintain glycemic control. Insulin glargine is a long-acting insulin injected once daily and provides a basal insulin level throughout the day. Regimens often combine it with rapid-acting insulin to obtain optimal glycemic control. The insulin should not be used to treat diabetic ketoacidosis, as short-acting insulin is preferred. This activity will cover the indications, mechanism of action, adverse effects, contraindications, monitoring, and toxicity of insulin glargine pertinent for healthcare professionals.

Objectives:

Identify the mechanism of action of insulin glargine.

Determine the contraindications of insulin glargine.

Apply the appropriate monitoring for insulin glargine.

Communicate some interprofessional team strategies for improving care coordination and communication to advance treatment with insulin glargine and improve outcomes.

Access free multiple choice questions on this topic.
Indications

Insulin glargine is a synthetic version of human insulin that is FDA-approved to improve and maintain glycemic control in adults and children with type 1 diabetes and adults with type 2 diabetes. It is a long-acting insulin injected once daily that provides a basal insulin level throughout the day. Regimens often combine it with rapid-acting insulin to obtain optimal glycemic control. The insulin should not be used to treat diabetic ketoacidosis, as short-acting insulin is preferred.

In type 1 diabetes, long-acting and short-acting insulins are often necessary at the onset of the disease. In this condition, the body lacks the ability to produce insulin from the pancreas due to autoimmune-mediated beta cell destruction, resulting in a rapid loss of regulation of blood glucose levels. Insulin glargine functions as basal glycemic control due to its 24-hour duration of action, while rapid-acting insulin works as coverage of elevated blood glucose and carbohydrate intake due to its quick onset and short duration of action.

In adults with type 2 diabetes, insulin glargine, or another long-acting insulin, should be initiated for glycemic control after 2 or 3 oral antidiabetic medications have failed to attain glycemic control or in patients with a hemoglobin A1c value higher than 9% experiencing symptoms. Insulin glargine may be used alone in individual patients or with rapid-acting insulin or oral medication(s) for diabetes management. Insulin glargine does not have approval for children with type 2 diabetes.[1]

Insulin glargine is not FDA-approved in pregnancy, although studies have not shown contraindications to its use or adverse fetal outcomes. It is considered a first-line treatment for gestational diabetes after lifestyle modifications have proven insufficient.[2][3]

Mechanism of Action

Insulin glargine is a recombinant human insulin analog that binds to receptors (IR). Insulin is necessary to regulate lipid, glucose, and energy homeostasis. It acts mainly on the skeletal muscle, adipose tissue, and liver. The IR is a tyrosine kinase receptor with 2 extracellular alpha domains and 2 intracellular catalytic beta domains. Upon insulin binding, a conformational change occurs to the beta catalytic domains that activate the tyrosine kinase domains, causing them to auto-phosphorylate the beta subunits. Once activated, the beta subunits can bind docking proteins, which leads to the activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3k) and an intracellular signaling cascade, eventually activating protein kinase B (also known as Akt). Akt regulates the activity of the glucose transporter type 4 (GLUT4) receptor, protein kinase C (PKC), and the mitogen-activated protein kinase (MAPK or MAP kinase) pathway.[4]

Insulin glargine has an onset of action of 1.5 to 2 hours. It has a long duration of action of up to 24 hours due to modifications of amino acids, including Asn to Gly at position 21 of the A chain and the addition of 2 Arg residues and positions 31 and 32 of the B chain. This arrangement allows the insulin to remain soluble at a pH of 4.0, the pH of the solution in which it is administered, and then become insoluble at physiologic pH. Once insulin glargine is injected into the body and introduced to the higher pH, the insoluble precipitate that forms slowly releases soluble protein over 24 hours.[5]

Administration

Insulin glargine comes either in 100 ml vials or dosing pens containing 3 ml cartridges of medication and is administered via subcutaneous injection only. The drug is available at a concentration of 100 units per ml. Its administration includes a diluent with a pH of 4.0 to maintain the solubility of the drug before use. The medication is administered once daily at the same time of day by the patient. Decisions of when to administer insulin glargine depend on the patient's schedule and the effect of insulin on the patient's blood glucose levels. Patients should rotate injection sites to avoid lipodystrophy; these include the top of the thighs, back of the upper arms, buttocks, or abdomen.

The estimated starting dose of insulin therapy is usually 0.4 to 0.5 units/kg per day of total insulin. However, differing amounts might be necessary for patients undergoing puberty or those with obesity. The consensus regarding basal insulin dosing is that it should make up 50% of the total daily insulin requirement. However, it is worth noting that recent studies have suggested that a basal dose closer to 40% of total daily insulin may result in more optimal glycemic control.[6]

Adverse Effects

The most common adverse effect of insulin glargine is hypoglycemia. Special attention is necessary for insulin usage in fasting patients who have recently changed their diets or have had recent activity changes, such as beginning a workout program. Hypoglycemia characteristically demonstrates autonomic symptoms, including diaphoresis, nausea, palpitations, tremors, anxiety, lethargy, and decreased concentration, among others. With severe hypoglycemia, unconsciousness, seizures, coma, and death may occur. Adverse effects may also include allergic reactions to the diluent, site injection reactions or infection, and lipodystrophy at the injection site. Insulin glargine may also cause pain upon injection at the site due to the acidity of the diluent.[7]

It is also essential to be aware of medications administered concurrently with insulin glargine. Certain medications can increase the risk of hypoglycemia when given concomitantly with insulin. Certain medications may also diminish the effectiveness of insulin glargine, causing hyperglycemia or masking symptoms of hypoglycemia. The risk of hypoglycemia may increase with the coadministration of antidiabetic drugs, other insulins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, propoxyphene, salicylates, sulfonamide antibiotics, and somatostatin analogs. The effectiveness of insulin glargine may diminish when administered with atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, isoniazid, niacin, phenothiazines protease inhibitors, somatotropin, sympathomimetic agents, and thyroid hormone replacements.[8]

Another concern regarding drug interactions includes the possibility of medications such as beta-blockers, clonidine, guanethidine, and reserpine masking symptoms of hypoglycemia. Lastly, thiazolidinediones have an increased risk of causing dose-related fluid retention when administered with insulin.

Contraindications

Insulin glargine is contraindicated in patients with a documented hypersensitivity to the drug or 1 of its components. It also should not be administered during a hypoglycemic episode. However, patients can restart the medication once the episode has resolved. Caution is advisable in infection, hypokalemia, kidney dysfunction, and liver disease.[9]

Insulin glargine is considered safe during pregnancy, and there are no known risks of infant harm if using the medication during lactation. However, the FDA lists insulin glargine as category C in pregnancy, stating that the patient should only use it if the benefits outweigh the risks.[10][2][10][2]

Monitoring

There is no specific safe range for insulin glargine as the dose is adjusted individually and depends on factors specific to the individual, including responsiveness to the insulin, diet, and daily routine. Other contributing factors that merit consideration during dosing include the type of diabetes, body weight, compliance, and rate of medication elimination. Safety issues that can arise include confusing insulin glargine with another insulin the patient takes concurrently. If an individual takes an inappropriate insulin dose, they are at high risk of suffering severe hypoglycemia.

The effects of insulin glargine are monitored on an outpatient basis utilizing a glucometer or continuous glucose monitor to follow blood glucose trends. The dosing of insulin depends on those findings. Continuous glucose monitors are becoming a more popular means to monitor blood glucose levels and the efficacy of an insulin regimen.[11]

Toxicity

Overdose of insulin glargine leads to hypoglycemia, which can be severe and persistent due to the long-acting nature of this insulin. In the case of mild hypoglycemia, carbohydrate intake is typically sufficient to restore euglycemia. The patient should ingest 15 grams of carbohydrates, wait 15 minutes, and recheck their blood glucose level. If it remains hypoglycemic, the procedure is repeated. In the case of severe hypoglycemia or if there is a reason that oral intake is not possible, then injectable glucagon is an option. Another option typically reserved for severe hypoglycemia in the hospital or EMS setting is intravenous dextrose. From published reports, dextrose infusion alone was sufficient to correct hypoglycemia. The long-acting nature of the insulin must also merit consideration; dextrose infusions may need to be repeated beyond the predicted 24-hour lifetime of the medication.[12][13][14]

Enhancing Healthcare Team Outcomes

The increasing rates of type 2 diabetes and the relative paucity of endocrinologists mean that initiating glucose control in uncomplicated type 2 diabetes should be part of the routine practice of interprofessional healthcare teams. Ideally, these teams would comprise clinicians (MDs, DOs, NPs, PAs), practice nurses, pharmacists, and certified diabetes educators. Some obstacles to implementing such care within a primary interprofessional team include ambiguity of roles, uncertainty of competency, and poor communication. For example, there is some ambiguity in the role of the primary care versus specialist clinician in initiating insulin and determining which patients do or do not meet the criteria of 'complicated.' Furthermore, there are misunderstandings regarding the ability to administer, educate, and adjust insulin between clinicians, practice nurses, and diabetes nurse educators.

Finally, poor communication between professional categories can lead to inadequate care, such that physicians communicate better with other physicians than with practice nurses, etc. Overcoming the abovementioned obstacles can lead to better patient outcomes and improved safety. This study has some limitations due to its use of a convenience sample of providers. Also, the study focused on provider factors that affect patient outcomes and did not consider any factors that may have impacted patient outcomes.[15] However, all of these factors point towards interprofessional team management of diabetes in general and the use of insulin glargine specifically, driving better patient outcomes.

References

Disclosure: Abigail Cunningham declares no relevant financial relationships with ineligible companies.

Disclosure: Andrew Freeman declares no relevant financial relationships with ineligible companies.

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Insulin glargine is a synthetic version of human insulin that is FDA-approved to treat adults and children with type 1 diabetes and adults with type 2 diabetes to improve and maintain glycemic control. Insulin glargine is a long-acting insulin injected once daily and provides a basal insulin level throughout the day.

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Depression is one psychosocial issue you may deal with when having Type 2. One treatment for this would be seeing a therapist on a regular basis. They will help you with coping, stress related to your disease, as well as how to move forward in a more positive manner. Therapists and Psychiatrists can help in this situation.

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Eating disorders can cause many different repercussions for people affected by them, including malnutrition, electrolyte imbalance, and cardiac issues. These issues can be accompanied by depression and anxiety to make issues more severe. Treatment for this combination of eating disorders and diabetes is difficult,as it requires balance between both conditions in order to achieve baseline glycemic levels. Behavioral therapy is recommended to find a healthy relationship with food.

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Abstract

Eating disorders and diabetes mellitus are distinct yet closely linked health conditions, presenting distinct challenges in terms of care and management. Eating disorders encompass a spectrum of mental health disorders characterized by abnormal eating behaviors and disruptions in weight regulation. Research indicates that individuals with diabetes might be at an elevated risk of developing eating disorders. The necessity to adhere to specific dietary guidelines, monitor blood sugar levels vigilantly, and manage drug administration can collectively contribute to the emergence of detrimental attitudes toward food and body image. On the other hand, incorrect eating behaviors such as binge eating and purging can disrupt blood sugar control, significantly impacting the development and management of diabetes. This intricate relationship emphasizes the crucial necessity for a comprehensive understanding and specialized care to effectively address the dual challenges faced by individuals dealing with both diabetes and eating disorders. This paper represents the inaugural comprehensive review delving into the intricate connection between eating disorders and diabetes, thereby illuminating previously under-researched areas. The insights gleaned from this review may contribute to developing integrated interventions that aim to improve the overall well-being and quality of life for individuals grappling with the complexities of eating disorders and diabetes.

Keywords: eating disorders, diabetes, mental disorders, integrated care, healthcare challenges

1. Introduction

Eating disorders (EDs) are serious and complex mental health conditions that impact an individual's relationship with food and their body image. Despite the first documented description of an eating disorder over three hundred years ago, the issue continues to persist and even increase globally [ 1]. Eating disorders affect at least 9% of the global population, making them one of the most prevalent mental health disorders [ 2, 3]. The onset of most eating disorders is typically in adolescence or early adulthood, with a median age of onset ranging from 18-22 [ 4]. The ratio of males to females in eating disorders ranges from 1:2 to 1:4, depending on the specific diagnosis [ 5]. The factor determining the higher percentage of morbidity among women is that women set themselves the goal of achieving a slim, slender figure, while men are dominated by the idea of a large, muscular body. Women generally have higher standards and pressure to be attractive. While men have a tendency to consume more foods with high calorific value, women usually restrict their calories [ 6]. Furthermore, research indicates a higher incidence of eating disorders in women compared to men, which could potentially be attributed to variations in brain function, which might foster the impulsive and repetitive behaviors commonly associated with eating disorders [ 7, 8]. Furthermore, eating disorders exhibit the highest mortality rate among all psychiatric disorders, surpassing even dysthymia, bipolar affective disorder, and schizophrenia, with a rate of 5.6% per decade [ 9]. A crucial factor contributing to this elevated risk is the significant disparity between men and women when it comes to seeking treatment (American Addiction Centers, n.d.). Specifically, men are notably less inclined to seek help for their eating disorders, which can lead to delayed or inadequate intervention and worsen their overall prognosis.

It is important to note that anorexia nervosa is becoming increasingly prevalent and may soon become the third most common chronic disease in adolescent girls aged 15-19, after obesity and asthma [ 10]. Statistics reveal that around 26% of individuals grappling with eating disorders make suicide attempts [ 9, 11]. This distressing finding underscores the severity of the mental health challenges faced by those affected by eating disorders and emphasizes the urgent need for effective intervention and support to prevent such tragic outcomes. Shockingly, research shows that there is no shortage of diagnosed individuals as young as nine or ten years old [ 12]. In the UK, the disorder is even recognized among preschoolers [ 13]. According to Wojtyła et al. 2011 study [ 14], approximately 33% of teenagers in Poland have attempted to lose weight using different methods, including drastic measures, and every second girl and every fourth boy believe that they are too fat [ 15]. Over the last twenty-seven years, Poland has moved up six units in the rankings, placing 106th in the world [ 16]. Such a significant increase may be due to an increasingly irregular lifestyle associated with excess work and stress, resulting in unsuitable nutritional patterns [ 17].

The causes of eating disorders are complex and multifaceted and may involve a combination of genetic and environmental psychological factors and vary from person to person. Some individuals may be more predisposed to developing an eating disorder due to genetics, while others may turn to disordered eating as a way to cope with stress, trauma, or other emotional challenges. In recent years, there has been growing interest in epigenetic factors, which may play an important role in both eating disorders and diabetes. These epigenetic modifications may affect the expression of genes that regulate insulin production, insulin sensitivity, appetite regulation, and areas of the brain responsible for reward and emotion [ 17]. Changes in these genes may contribute to the development of obesity and type 2 diabetes. Growing evidence suggests that epigenetic changes that occur during fetal development in response to factors such as maternal nutrition and stress may increase the risk of diabetes later in life [ 17, 18, 19]. Additionally, epigenetic changes may affect the body's response to stress, which is a known cause of some eating disorders. In addition to genetic and epigenetic influences, psychological factors are crucial contributors to eating disorders [ 8]. Societal pressure to conform to a certain body type or appearance can also contribute to the development of eating disorders, especially in a world where social media and unrealistic body standards play a significant role in the self-esteem of young people. Additionally, psychological trauma resulting from marginalization by peers, comments about appearance, or comparing body shapes and sizes may also contribute to dissatisfaction with one's appearance and the development of eating disorders [ 18].

Eating disorders impose substantial physical and psychological consequences on those affected. Among the common physical repercussions are malnutrition, electrolyte imbalances, and cardiac issues, which can pose serious health risks [ 19]. In addition to the physical toll, individuals with eating disorders often battle mental health challenges, such as depression and anxiety, further complicating their well-being. Moreover, these disorders can lead to social isolation, as individuals may withdraw from social situations involving food due to their struggles and fears surrounding eating [ 19]. This social avoidance can exacerbate feelings of loneliness and detachment from others. As a consequence of the combined physical, psychological, and social impacts, those with eating disorders may experience a significant decline in their overall quality of life. The disorders can create difficulties in various aspects of daily living, including relationships, work or school performance, and overall emotional well-being [ 19].

Recent epidemiological studies have shed light on the heightened risk of developing eating disorders, including bulimia, anorexia, and binge eating disorder, among individuals with diabetes [ 20, 21, 22]. It turns out that eating disorders and diabetes mellitus are distinct yet intricately interconnected health conditions. The need to follow precise dietary guidelines, diligently monitor blood sugar levels, and manage medication administration can collectively contribute to the development of detrimental attitudes toward food and body image. Conversely, maladaptive eating behaviors such as binge eating and purging can disrupt blood sugar control, thereby significantly affecting the onset and management of diabetes.

Diabetes and eating disorders create a complex and potentially dangerous combination of conditions that can lead to increased morbidity and mortality. Those with both conditions face the challenge of maintaining a healthy weight and controlling blood sugar levels, creating a vicious cycle that can result in further complications such as cardiovascular disease, nerve damage, and kidney failure [ 23, 24, 25]. The psychological toll of eating disorders, such as stress, anxiety, and depression, can further exacerbate diabetes management [ 24].

The primary objective of this review was to assess the relationship between eating disorders and diabetes mellitus, acknowledging the unique but interconnected nature of these two conditions. The primary objective of this review was to conduct a thorough and comprehensive analysis of the potential relationship between eating disorders and diabetes. Additionally, our objective was to elucidate the factors contributing to the emergence of eating disorders among individuals affected by diabetes. Moreover, we aimed to assess how the control of blood sugar levels and the psychological facets of disordered eating impact the holistic treatment and well-being of those confronting both diabetes and eating disorders. The insights gathered in this review have the potential to offer valuable guidance in shaping comprehensive interventions, which could be of great importance due to their practical implications in clinical medicine. These interventions aim to holistically enhance the overall will lead to improvements in the quality of life and well-being for individuals who grapple with the intricate challenges posed by a dual diagnosis.

2. Diabetes and Disordered Eating Behaviors/Eating Disorders

Diabetes, as a chronic metabolic condition, presents unique challenges in relation to the development and management of eating disorders. Over the years, extensive research has provided valuable insights into the prevalence of eating disorders among individuals with diabetes, uncovering significant patterns and risk factors associated with this population [ 26, 27, 28].

2.1. Disordered Eating vs. Eating Disorder

While these terms share similarities, they are not interchangeable, and recognizing their differences is crucial ( Figure 1). An eating disorder is considered a clinical diagnosis that involves specific criteria related to the severity, degree, and frequency of disordered eating behaviors. On the other hand, disordered eating encompasses a range of problematic eating behaviors and attitudes that may not yet meet the criteria for a formal eating disorder diagnosis but still have the potential to negatively impact an individual's physical and psychological well-being.

Figure 1.

Similarities and differences between disordered eating and eating disorder.

By understanding the nuances between disordered eating and eating disorders, healthcare professionals can better assess and address the specific needs of individuals with diabetes who may be at different points along the spectrum of these conditions. Early recognition of disordered eating patterns can facilitate timely intervention and support, potentially preventing the escalation to a full-blown eating disorder and improving overall treatment outcomes for those affected by diabetes and these eating-related challenges.

The constant focus on food as a crucial aspect of diabetes management closely ties individuals with diabetes to both disordered eating and eating disorders. Current scientific reports highlight a widespread occurrence of nutrition-related disorders and errors in people with type 1 diabetes, particularly when compared to age-matched individuals without hyperglycemia [ 29]. The main mistakes in the control and supervision of eating habits and, consequently, eating disorders are inconsistent and irregular insulin treatment. Ultimately, as a result of long-term incorrect treatment, this leads to a lack of glycemic control and, ultimately, an increase in the risk of complications [ 29]. In individuals diagnosed with both diabetes and an eating disorder, the onset of diabetes typically precedes the development of the eating disorder, especially in cases of type 1 diabetes. However, the reverse relationship may occur with type 2 diabetes, where the presence of an eating disorder, such as binge eating, can potentially contribute to the development of the disease. Among patients with type 1 diabetes, bulimia nervosa is the most common eating disorder observed. This disorder involves cycles of binge eating followed by maladaptive weight control behaviors. In contrast, individuals with type 2 diabetes more frequently exhibit binge eating without purging behaviors and may also experience the syndrome of night eating, characterized by waking up in the middle of the night to consume food. Anorexia nervosa, characterized by severe food restriction, is the least common eating disorder observed in this population but carries an alarmingly high mortality rate.

These are some common signs of disordered eating behaviors that may be observed in individuals with diabetes ( Table 1) [ 30].

Table 1.

Signs of Disordered Eating in Diabetes

Preoccupation with Food
-Constant thoughts about food, calories, and weight

Strict Meal Plans
-Following excessively rigid eating patterns and meal plans

Fear of High Blood Sugar
-Extreme anxiety or fear of elevated blood sugar levels and their consequences

Distorted Body Image
-Negative perception of body shape or size, even when it may not align with reality

Unhealthy Weight Control Behaviors
-Engaging in extreme weight control methods, such as skipping meals or purging

Withdrawing from social eating activities
-Knowingly or intentionally removing oneself from social gatherings or events that involve eating

Insulin Manipulation
-Intentional omission or underdosing of insulin to manipulate weight or blood sugar levels

Excessive Exercise
-Compulsive or excessive exercise routines as a means of compensating for food intake or controlling weight

Mood Swings or Emotional Distress
-Frequent mood changes, anxiety, depression, or irritability related to food, body image, or diabetes management

Early recognition and intervention are vital for addressing these issues and promoting the well-being of individuals with both diabetes and disordered eating, as these conditions can have significant impacts on their overall health and quality of life. Individuals with diabetes may be at an increased risk of developing eating disorders due to the complex relationship between food, body image, and diabetes management.

One type of eating disorder that may occur in individuals with diabetes involves severe dietary restriction ( Table 2). This behavior manifests as severely limiting calorie intake or eliminating essential macronutrients from the diet. The motive behind such restriction is often driven by a desire to control blood sugar levels or achieve weight loss [ 28]. Objective binge eating is another type of eating disorder observed in individuals with diabetes. It involves consuming an unusually large amount of food within a short period while experiencing feelings of being out of control. The binge episodes may be triggered by various factors and can lead to significant emotional distress. Subjective binge eating refers to losing control over eating without necessarily consuming large quantities of food. Individuals experiencing subjective binge eating may feel overwhelmed by their eating habits and struggle with emotional and psychological consequences, even if the physical volume of food consumed is not as extreme.

Table 2.

Types of Eating Disorders in Individuals with Diabetes

1. Severe Dietary Restriction
-Severe limitation of calories or essential macronutrients in the diet

2. Objective Binge Eating
-Consuming an unusually large amount of food in a short period while feeling out of control

3. Subjective Binge Eating
-Feeling a loss of control over eating without necessarily consuming large quantities of food

4. Other Maladaptive Weight Control Strategies
-Restricting life-saving insulin

In some cases, individuals with diabetes and an eating disorder may resort to other maladaptive weight control strategies. This can include restricting or manipulating life-saving insulin doses in an attempt to achieve weight loss. Such behaviors can be dangerous and have serious health implications.

2.2. Eating Disorders in Type 1 Diabetes

A comprehensive investigation conducted by Jones et al. 2000 [ 31] shed light on the prevalence of eating disorders among females with type 1 diabetes, revealing that only 10% of them were affected. These findings indicate that women diagnosed with type 1 diabetes are at a 2.4-fold higher risk of developing eating disorders compared to those without diabetes. Grylli et al. 2004 [ 32] found that 11.5% of female participants with type 1 diabetes had eating disorders, while none of the male participants exhibited such conditions. Similarly, an analysis of studies focusing on disordered eating behavior in adolescents and young adults showed a higher prevalence of such behaviors among individuals with type 1 diabetes compared to their peers [ 31, 33].

However, Meltzer et al. [ 34] presented contrasting results in their analysis. They suggested that individuals with diabetes, especially females, do not exhibit a higher susceptibility to eating disorders. In fact, females with diabetes reported lower levels of body dissatisfaction compared to the general population. Nonetheless, authors highlighted a heightened risk of developing disordered eating patterns among female patients aged 13-14 years [ 34].

Based on the available evidence, there is a suggestion that Type 1 Diabetes is more frequently observed prior to the development of restrictive eating disorders, particularly Anorexia Nervosa (AN) or Avoidant Restrictive Food Intake Disorder (ARFID) [ 31]. This finding indicates that individuals with Type 1 Diabetes may be at a higher risk of subsequently developing these specific forms of eating disorders.

2.2.1. Anorexia Nervosa

Anorexia nervosa (AN) is a serious eating disorder with significant physical and psychological consequences. It is characterized by extreme food restriction, a distorted body image, and a deep fear of gaining weight ( Table 3). Individuals with AN often have low body weight and severe malnutrition, and they may engage in excessive exercise or harmful purging behaviors, such as self-induced vomiting and laxative abuse [ 35].

Table 3.

Eating Disorders

Anorexia Nervosa (AN)

An unwillingness to maintain body weight above the minimum normal weight, which is typically around 85% of the expected weight or BMI is equal to or less than 17.5 for an individual's height and age according to the ICD-10 classification.

Severe disturbances in their body image, including a persistent fear of gaining weight or becoming fat, even when they are already underweight.

Multiple physical complications, starting from the skin-xerosis, acne, telogen effluvium, through gastric dilatation with evidence of mucosal necrosis, arrhythmias, acrocyanosis, sodium depletion, and hypovolemia.

Avoidant/Restrictive Food Intake Disorder (ARFID)

Limited interest or range of food choices, often due to sensory issues or negative experiences,

Symptoms are lack of interest in food, avoidance based on sensory characteristics of food, and concern about aversive consequences of eating as examples of features.

Bulimia Nervosa (BN)

Characterized by a cycle of binge eating followed by purging behaviors,

Binge eating occurs at least twice a week for three months (DSM-5),

Purging behaviors may include self-induced vomiting, fecal tenesmus, laxative use, or excessive exercise,

Individuals may have a normal or slightly above-average body weight.

Binge-Eating Disorder (BED)

Recurrent episodes of binge eating, during which a person eats a large amount of food in a short period of time and feels a lack of control over their eating,

People with binge eating disorders do not engage in purging behaviors, strongly associated with overweight and obesity.

Diabulimia

The intentional manipulation of insulin doses for the purpose of weight loss or weight control by individuals with type 1 diabetes,

Severe hyperglycemia and related complications

Several risk factors contribute to the development of AN. Those with a family history of AN or comorbid mental health conditions such as depression, anxiety, and substance abuse are at a higher risk of developing the disorder. Research indicates that individuals with a first-degree relative who has AN have a 10-fold greater risk of developing the illness themselves [ 36, 37, 38]. Additionally, social and environmental factors, such as societal pressure to conform to a specific body type, lack of support systems, and traumatic events, can also play a role in the onset of AN [ 35].

Adolescent girls and young women affected by AN often experience numerous physical complications. These may include skin issues such as xerosis and acne, telogen effluvium (hair loss), gastric problems such as dilatation with evidence of mucosal necrosis, arrhythmias (irregular heartbeats), acrocyanosis (bluish discoloration of extremities), sodium depletion, hypovolemia (low blood volume), and associated hemoconcentration (increased concentration of blood cells and plasma). Moreover, AN can lead to bone demineralization due to estrogen deficiency and body weight loss, which are likely the main factors contributing to the development of osteoporosis and osteopenia [ 39].

Incidence rates of anorexia nervosa (AN) can vary based on the study population and healthcare setting [ 40]. However, there are reports indicating an increase in AN cases among adolescent girls aged 10-14 years [ 40, 41]. A primary healthcare research study in Great Britain involving individuals aged 13-16 revealed a rise in diagnosed cases of AN in 2018 compared to analyses conducted in 2003 [ 16]. Current data suggest that up to 4% of females and up to 0.3% of males may experience AN at some point during their lives [ 16]. It is important to note that AN has the highest mortality rate of all psychiatric disorders and is associated with increased suicidality [ 13]. Early recognition and treatment of AN are crucial to prevent severe physical and psychological consequences.

Both diabetes mellitus and AN share a heightened awareness of carbohydrate consumption. When type 1 diabetes and AN are combined, publicly available data indicate elevated HbA1c levels and an increased risk of various acute and chronic complications [ 24]. The lack of stability and regularity in the patient's eating pattern is a common link between both disorders. Some studies have shown an increased risk of eating disorders, including AN, in individuals with diabetes, but the prevalence rates of comorbid AN with diabetes may not necessarily be significantly higher than in patients without diabetes ( Figure 2) [ 42].

Figure 2.

Prevalence of AN or BN with/without diabetes [ 42].

Managing the coexistence of diabetes and AN necessitates a comprehensive approach that addresses the unique challenges posed by both conditions. Early identification, intervention, and ongoing support are crucial to improving the outcomes and well-being of individuals facing this complex dual diagnosis.

2.2.2. Avoidant/Restrictive Food Intake Disorder

Avoidant/Restrictive Food Intake Disorder (ARFID) is a distinct eating disorder characterized by limited interest or a narrow range of food choices, often driven by sensory issues or negative experiences [ 43]. Unlike picky eating in preschoolers, restrictive eating behaviors in ARFID are not motivated by body image disturbances or a desire to lose weight ( Table 2). Individuals with ARFID may experience severe malnutrition and disruptions in psychosocial functioning as potential consequences.

The prevalence rates of ARFID vary across different populations. In clinical eating disorder populations, the rates range from 1.5% to 64%, as reported by several studies [ 44, 45, 46, 47, 48, 49, 50, 51]. However, in non-clinical populations, the rates are generally below 15.5% [ 52, 53, 54]. One noteworthy aspect is that ARFID primarily affects younger patients, and surprisingly, in comparison to other eating disorders, there is a significantly higher proportion of males affected by ARFID [ 55]. This highlights the importance of recognizing the unique features and demographics of ARFID to provide appropriate and targeted interventions for those affected.

2.2.3. Bulimia Nervosa

Bulimia Nervosa (BN) is a serious eating disorder characterized by a cycle of binge eating followed by purging behaviors. Binge eating episodes involve consuming large amounts of food within a short period, and purging behaviors can include self-induced vomiting, the use of laxatives, enemas, or excessive exercise [ 56]. Individuals with bulimia nervosa may have a normal or slightly above-average body weight ( Table 3).

The etiology of bulimia nervosa is multifaceted, involving a combination of factors such as personality traits, biology, sociocultural influences, behavioral patterns, and family dynamics [ 56, 57]. There are two types of bulimia: laxative and non-laxative. Laxative bulimia involves the use of drugs and enemas in addition to self-induced vomiting, while non-laxative bulimia involves regular excessive exercise and restrictive eating.

If left untreated, bulimia nervosa can have significant negative consequences on both mental and physical health. Physical complications may include weakness, diarrhea, constipation, headaches, anemia, dental issues such as the destruction of tooth enamel, gastrointestinal problems such as gastroesophageal reflux disease, esophagitis, and gastritis, as well as nutritional deficiencies [ 56].

Bulimia nervosa can affect individuals of all ages and genders, but it is most prevalent in the 15-29-year-old age group. The incidence of bulimia nervosa is generally lower in men than in women, with a sex ratio of about 1:10 [ 58, 59]. Studies have shown that up to 3% of females and more than 1% of males may be affected by bulimia nervosa [ 60].

The mortality risk associated with bulimia nervosa is comparable to that of anorexia nervosa and is linked to cardiovascular problems [ 61], a higher risk of suicide [ 11, 62], as well as other complications involving the gastrointestinal, endocrine, and renal systems [ 63].

2.2.4. Diabulimia

Diabulimia is a dangerous and concerning eating disorder commonly observed in individuals with type 1 diabetes. It involves the intentional omission or reduction in insulin to lose weight or prevent weight gain. As insulin is essential for regulating blood sugar levels in individuals with type 1 diabetes, reducing or omitting insulin leads to elevated blood sugar levels, causing the body to break down fat for energy, resulting in weight loss, which may be the desired outcome for some individuals. Several studies have reported that the fear of weight gain is a core component in the emergence of insulin mismanagement [ 64, 65]. However, the act of reducing or omitting insulin can have severe consequences. Prolonged high blood sugar levels can lead to diabetic ketoacidosis, a life-threatening condition requiring immediate medical attention. Additionally, persistently elevated blood sugar levels can lead to various complications, such as nerve damage, kidney damage, and vision problems [ 28]. The symptoms of diabulimia can vary depending on the duration and severity of the condition ( Table 4).

Table 4.

Diagnosed Duration

Symptoms

Short term

-
polyuria with ketonuria,

-
polyphagia,

-
polydipsia,

-
high blood glucose (more than 250 mmol/L, but less than 600 mmol/L),

-
weakness,

-
fatigue

-
poor concentration,

-
unbalanced concentration of electrolytes (high potassium or low sodium)

Medium-term

-
dehydration (moderate to severe),

-
high blood glucose (more than 250 mmol/L, but less than 600 mmol/L),

-
weight loss,

-
muscle atrophy,

-
indigestion,

-
gastroesophageal reflux disease,

-
edema

Long term

-
high blood glucose (more than 250 mmol/L, but less than 600 mmol/L),

-
kidney damage (nephropathy),

-
neuropathy,

-
blindness (retinopathy),

-
extreme fatigue,

-
high levels of cholesterol conducing to cardiovascular problems,

-
osteoporosis

Diabulimia is often linked to emotional and psychological difficulties [ 67]. Individuals with diabetes who engage in diabulimic behaviors may experience intense guilt, shame, and anxiety concerning their eating habits and diabetes management. The complex interplay between diabetes and disordered eating can create a detrimental cycle where the pursuit of weight control leads to worsened diabetes management, an increased risk of complications, and further deterioration of psychological well-being.

The consequences of diabulimia are severe, and individuals who omit insulin are found to be at three times greater risk of premature death than those who adhere to their prescribed treatment. Early detection and comprehensive intervention are crucial to addressing diabulimia and providing individuals with the necessary support to manage both their diabetes and disordered eating behaviors.

2.3. Eating Disorders in Type 2 Diabetes

Individuals with type 2 diabetes are also susceptible to the risk of developing eating disorders. Patients with type 2 diabetes often experience overweight or obesity, which may be correlated with bad eating habits and episodes of binge eating. These behaviors can negatively impact blood sugar control and overall health [ 68].

Some individuals with type 2 diabetes may have irregular meal timing, such as skipping meals or eating at inconsistent intervals. Irregular meal timing can lead to unstable blood sugar levels, making it challenging to achieve glycemic control. Skipping meals, especially breakfast, can affect insulin sensitivity and increase the risk of hypoglycemia or hyperglycemia [ 28]. Restrictive eating behaviors, excessive exercise, and purging can lead to irregular and unpredictable blood glucose levels. This makes it challenging to maintain stable glycemic control and can increase the risk of hyperglycemia or hypoglycemia. Further, excessive exercise and purging can lead to irregular and unpredictable blood glucose levels. This makes it challenging to maintain stable glycemic control and can increase the risk of hyperglycemia or hypoglycemia. What is more, depressive symptoms and behaviors can contribute to eating disorder development, especially in patients with diabetes (occurrence is two to three times higher-Bădescu et al., 2016) [ 69]. Individuals with depression experience varying appetite changes due to their depressive symptoms, which may leave them vulnerable to disordered relationships with food.

2.3.1. Binge Eating Disorder

A binge eating disorder (BED) is a significant mental health condition characterized by recurrent episodes of binge eating, where individuals consume large amounts of food in a short period while feeling a lack of control over their eating behavior. Unlike bulimia nervosa, individuals with BED do not engage in purging behaviors such as vomiting or excessive exercise. The WHO Global Mental Health Study found that BED has a higher prevalence rate compared to bulimia nervosa and anorexia nervosa ( Figure 1) [ 70]. Giel et al., 2022 [ 71] estimated that binge eating disorder (BED) affected around 0.6-1.8% of adult women and 0.3-0.7% of adult men globally between 2018 and 2020. Unlike bulimia, people with binge eating disorders do not engage in purging behaviors [ 72]. Due to the caloric overconsumption involved, BED is strongly associated with overweight and obesity, which leads to a high body mass index (BMI). Individuals with BED have significantly higher current BMI than respondents without a history of eating disorders: 2.6% (BMI = 30-35) and 4.5% (BMI ≥ 35) in obese subjects, respectively. BED can also lead to medical complications such as type 2 diabetes, high blood pressure, and heart disease [ 71].

Research indicates that binge eating behaviors are observed in approximately 7% to 20% of individuals diagnosed with type 2 diabetes [ 73, 74, 75], with around 8% receiving a clinical diagnosis of BED [ 76]. Furthermore, approximately one-third of individuals with BED also have coexisting type 2 diabetes [ 77] ( Figure 3). Remarkably, a significant proportion ranging from 10% to 40% of individuals diagnosed with type 2 diabetes may fulfill the diagnostic criteria for an eating disorder, with Binge Eating Disorder (BED) being the predominant subtype [ 77].

Figure 3.

Period prevalence of BED with/without diabetes [ 77].

Treatment for BED typically involves psychotherapy, such as cognitive-behavioral therapy or interpersonal therapy, and medication may also be used in some cases. In addition to these treatments, lifestyle changes such as improving sleep habits, increasing physical activity, and adopting healthy eating habits can also be helpful [ 78].

2.3.2. Diarexia

Diarexia, sometimes referred to as "diabetic anorexia," is another eating disorder commonly observed in individuals with diabetes, both type 1 and type 2. It involves the restrictive eating of food in an effort to maintain blood sugar control. People with diarexia may limit their food intake excessively, leading to inadequate nutrition and energy for proper diabetes management. They may prioritize blood sugar control over overall health and well-being, resulting in weight loss, malnutrition, and potentially severe complications. The patients usually intentionally reduce insulin intake, which leads to poor metabolic control and serious complications, such as neuropathy, retinopathy, nephropathy, and an increased incidence of hospital admissions due to ketoacidosis [ 79]. Comorbid anorexia with diabetes mellitus type 1 comes with a significantly raised mortality rate (34.7 per 1000) compared to patients with only anorexia (7.7 per 1000) or type 1 diabetes (2.2 per 1000) researched by Søren et al., 2002 [ 80]. Diarexia is a much lower incidence in diabetic females than diabulimia [ 42]; it is still a severe condition leading to an increased risk of complications and death.

2.3.3. Night Eating Syndrome

Night Eating Syndrome (NES) is an eating disorder characterized by recurrent episodes of eating at night, either by waking up from sleep and eating or consuming a large amount of food after an evening meal. The clinical definition of NES, as described by Stunkard et al., 1955 [ 81], includes a triad of symptoms: morning anorexia (reduced appetite in the morning), evening hyperphagia (consuming 25% of total energy intake after 7 pm), and insomnia. If left untreated, NES can lead to difficulties in maintaining a healthy weight and may result in conditions such as type 2 diabetes and high blood pressure. The prevalence of NES is estimated to be around 1 in 100 individuals.

Research indicates that NES is more prevalent among individuals with type 2 diabetes, with prevalence rates ranging from 3.8% to 8.4%. Surprisingly, there may not be a significant difference in body mass index (BMI) between people with and without diagnosed NES, despite the association between NES and weight-related issues. NES may contribute to weight gain, particularly in individuals susceptible to obesity [ 82].

The exact causes of NES are not fully understood, but researchers believe it may result from various factors, including circadian rhythm disorders (disturbances in the body's internal clock), depression and anxiety, daytime dieting, and genetic predisposition [ 83].

Treatment for NES typically involves a multidisciplinary approach, including psychotherapy and nutritional counseling. Behavioral therapies aim at establishing regular eating patterns, and addressing nighttime eating behaviors can be beneficial in managing NES. Additionally, identifying and addressing any underlying emotional or psychological factors is essential in the treatment process.

2.3.4. Orthorexia Nervosa

Orthorexia nervosa (ON) is one of the unclassifiable eating behavior disorders and is briefly defined as an obsession with healthy eating [ 84]; it is an undeniably fast-spreading problem. Although not specific to diabetes, orthorexia is characterized by an exaggerated and prolonged obsession with adhering to strict dietary practices, often based on evidence-based or non-evidence-based information, in the pursuit of optimal health [ 85]. The distinguishing factor between healthy eating and ON lies in the severity of restrictive dietary behaviors and the level of self-discipline surrounding one's diet. In ON, the focus is not solely on the quantity of food consumed but rather on the perceived quality of the food [ 86]; fixation can lead to obsessive behaviors related to sourcing, preparing, and consuming specific types of food, which may ultimately negatively impact various aspects of an individual's life.

An exaggerated food intake restriction and the elimination of specific food groups, such as meat, dairy, grain, cooked food, and non-seasonal produce [ 87, 88], may lead to severe complications such as a lack of essential nutrients and malnutrition, which can transform into gastrointestinal problems, hormonal imbalances, general fatigue, and a weakened immune system [ 89] but also anemia, or an abnormally slow heart rate [ 90].

Factors affecting the risk of ON and diabetes self-management can indeed be intertwined. People with Type 2 Diabetes Mellitus (T2DM) often have to follow strict dietary guidelines to effectively manage their blood glucose levels. This can include monitoring their carbohydrate intake, portion control, and adhering to specific meal plans. However, the focus on maintaining a healthy diet in diabetes management can sometimes lead to orthorexic tendencies. The strict rules and restrictions associated with diabetes self-management may trigger obsessive thoughts and behaviors around food quality and purity [ 91]. These individuals may become overly fixated on only consuming "healthy" foods and avoiding any perceived "unhealthy" or "impure" choices, which can contribute to the development or exacerbation of ON. Therefore, it is important to address and control orthorexic tendencies while simultaneously promoting effective diabetes self-management. This can be achieved through a balanced approach that focuses on education, support, and psychological well-being.

2.3.5. Pregorexia

Pregorexia is a term that is informally used to describe disordered eating behaviors occurring during pregnancy. It is not officially recognized as a medical diagnosis in the Diagnostic and Statistical Manual of Mental Disorders (DSM) or other medical diagnostic manuals [ 92]. Some experts use the term pregorexia to refer to a subset of eating disorders, such as anorexia nervosa, bulimia nervosa, or binge eating disorder, that can either develop or worsen during pregnancy. However, there is an ongoing debate and lack of consensus among experts regarding the precise definition and diagnostic criteria for pregorexia. As a result, the term is not a standardized medical diagnosis. Women with preexisting eating disorders, such as anorexia, bulimia, or binge eating disorder, may experience challenges in managing their conditions during pregnancy. Pregnancy can trigger or exacerbate disordered eating behaviors, which can pose significant risks to both the mother and the developing fetus. For pregnant women with diabetes, there is also a potential risk of developing disordered eating behaviors. These behaviors can manifest as restrictive eating, extreme dieting, excessive exercise, or an unhealthy preoccupation with weight and body image during pregnancy. Disordered eating behaviors during pregnancy can lead to several adverse outcomes for both the mother and the baby. Nutritional deficiencies, such as iron deficiency leading to anemia, can affect the mother's health and increase the risk of postpartum depression [ 93]. Additionally, these behaviors can result in increased risks of caesarian sections, miscarriage, low birth weight, microcephaly, and even infant mortality [ 94, 95, 96].

3. Treating Eating Disorders and Diabetes-The Dual Challenge

Treating individuals with both eating disorders and diabetes presents a dual challenge that necessitates a comprehensive approach that includes psychotherapy, glycemic control, nutritional counseling, and diabetes education [ 28]. For individuals with both type 2 diabetes and binge eating disorder (BED), daily challenges arise from conflicting medical and nutritional recommendations. While weight loss and energy deficit are emphasized to improve diabetes outcomes, BED treatment focuses on establishing a healthy relationship with food and reducing binge eating episodes [ 97]. Balancing these conflicting recommendations becomes difficult for those navigating both conditions. Hence, treatment teams must adopt an integrated approach that acknowledges and addresses both conditions, devising personalized strategies that cater to each individual's unique needs. This approach takes into account the potential impact of dietary recommendations on both disorders, finding a middle ground between managing blood sugar levels and promoting a healthy relationship with food, ultimately enhancing overall well-being and quality of life. One of the considered methods is lifestyle behavioral changes, diet, behavioral therapy, and physical activity in order to obtain ≥5% weight loss and maintain it, which is recommended for patients with type 2 diabetes and obesity. It should include a high frequency of counseling and a more individual approach individualized to the patient. It needs to be focused on dietary changes, physical activity, and behavioral strategies to reach an energy deficit (500-750 kcal per day). For those who achieved weight loss goals, it is recommended to receive long-term maintenance programs [ 98]. Weight loss might not be enough to maintain it long-term. That people could benefit from additional pharmacotherapeutic options, such as Metformin, α-glucosidase inhibitors, liraglutide, thiazolidinediones, testosterone [ 99], and insulin [ 97]. Additionally, providers should consider the other drugs that patients use and, if possible, reduce or give alternatives for medications associated with weight gain, such as some antipsychotics, antidepressants etc. [ 100]. Prioritizing blood sugar level management is essential in diabetes care, and the treatment plan should include strategies for monitoring blood glucose levels, adjusting insulin dosages or types of antidiabetic medications, and ensuring adequate nutrition to maintain stable blood sugar levels. Dietitians play a critical role in providing education on balanced nutrition for managing diabetes while also addressing disordered eating patterns. Collaborating closely with individuals, dietitians develop personalized meal plans that meet nutritional needs and support the recovery process. It is important that recommendations should not be overly strict to avoid increasing the risk and frequency of binge eating episodes [ 21]. In cases where patients are overweight or obese, it is essential to prioritize treating the eating disorder before focusing on weight loss [ 101].

In individuals with type 1 diabetes, the presence of eating disorders often involves dangerous behaviors such as insulin restriction to control weight. However, this practice significantly increases the risk of complications. Therefore, treatment approaches should prioritize promoting healthy eating habits and regular blood glucose monitoring to manage diabetes effectively. Some individuals with eating disorders and type 1 diabetes may avoid testing their blood glucose regularly or altogether due to anxiety about high blood sugar levels. This behavior, known as test denial, can be an expression of anger or denial towards their illness. In severe cases, hospital admission may be necessary to control insulin use and stabilize eating habits. During hospitalization, nursing staff may temporarily take over insulin administration if concerns arise regarding the patient's honesty about insulin administration.

What is more, a thorough assessment of the individual's medical and psychiatric history, eating behaviors, blood sugar control, nutritional status, and mental health is essential. The psychological and emotional aspects of eating disorders can present challenges to the management of diabetes. Mental health conditions such as anxiety, depression, and distorted body image can influence self-care behaviors and adherence to diabetes treatment plans. In addressing these challenges, psychiatrists and psychopharmaceuticals, such as fluoxetine and topiramate, may be valuable in identifying and treating anxiety and binge eating episodes related to eating disorders. Emotional distress can also contribute to disordered eating patterns and unhealthy coping mechanisms. Several studies have reported that the fear of weight gain is a core component in the emergence of insulin mismanagement in T1DM patients [ 102]. Taking these factors into account is crucial for comprehensive care and successful management of both eating disorders and diabetes. Cognitive-behavioral therapy (CBT), dialectical behavior therapy (DBT), or interpersonal therapy are essential components of the treatment plan, helping individuals foster healthier relationships with food and their bodies. Cognitive behavioral therapy (CBT) has shown long-term effectiveness in reducing the frequency of binges and improving glycemic control, as demonstrated in studies by Kernardy et al., 2002 [ 103]. Therefore, it is crucial to address both conditions simultaneously for optimal outcomes. Regular follow-up visits and monitoring of progress are necessary to track the individual's physical and mental health, make adjustments to the treatment plan as needed, and provide ongoing support [ 104].

Unfortunately, there is limited research on the psychological treatment of eating disorders in individuals with type 1 diabetes. Some studies have shown potential improvements when patients receive psychoeducation, family therapy, or cognitive-behavioral therapy (CBT). However, a recent systematic review suggested that these interventions might be ineffective in improving glycemic control [ 105]. Conventional CBT may yield inferior outcomes and higher dropout rates in individuals with both diabetes and bulimia compared to those with only bulimia nervosa [ 26]. Addressing the complex interplay between type 1 diabetes and eating disorders requires further research and the development of tailored interventions that consider the unique challenges posed by these dual conditions. Keep in mind that the presence of eating disorders in individuals with diabetes may be associated with an increased risk of mortality. A study conducted using female patient registries in Scandinavia investigated the mortality rates over a 10-year follow-up period. The findings revealed that among patients with type 1 diabetes, the mortality rate was 2.2 per 1000 person-years. In individuals with only anorexia, the mortality rate was 7.3 per 1000 person-years. Alarmingly, for patients who had both type 1 diabetes and anorexia concurrently, the mortality rate significantly increased to 34.6 per 1000 person-years [ 106]. These results emphasize the seriousness of the comorbidity and the importance of addressing both diabetes and eating disorders to ensure the well-being and longevity of affected individuals.

In conclusion, this review underscores the intricate connection between eating disorders and diabetes, shedding light on the imperative need to recognize and understand their multifaceted interplay. Eating disorders have become an unsettling and pervasive concern of health. The surge in their prevalence is influenced by a myriad of factors, including the rapid advancement of technology, the perpetuation of societal ideals propagated through diverse media platforms, low self-esteem, the prevalence of extreme dieting culture, genetic predisposition, and the presence of metabolic disorders such as diabetes. The symbiotic relationship between eating disorders and diabetes is characterized by a dynamic feedback loop wherein the presence of one condition can profoundly influence the course and outcomes of the other, resulting in a complex web of physiological, psychological, and behavioral interactions. Effectively addressing this complex issue demands early recognition and precisely targeted therapeutic intervention.

The insights gleaned from this comprehensive review may serve as a valuable wellspring of information for the development of new strategies that take into account the intricate dynamics shared by eating disorders and diabetes. The reflections gathered in this comprehensive review can provide a significant source of information for developing new strategies that address the complex dynamics common to eating disorders and diabetes. This review clearly highlights the importance of early diagnosis, shedding light on its potential benefits. As a result, healthcare professionals can increase their vigilance in detecting eating disorders and diabetes at an early stage. This is expected to translate into faster interventions that are often more effective and less invasive.

It is worth noting, however, that in addition to the diagnosis itself, the article also addresses the need for personalized therapeutic interventions in patients with eating disorders and diabetes. This approach may result in better treatment outcomes and increased adherence to treatment plans. The review also highlights the interdependence of these disorders, encouraging close collaboration between different healthcare professionals, such as nutritionists, endocrinologists, and mental health professionals. Working together, they can develop holistic treatment plans that take into account both the nutritional and psychological aspects of these conditions.

However, while this analysis takes into account the complexity of the problem, it does not provide specific recommendations or practical guidance for healthcare professionals. We realize that the article does not identify the gaps in previous research, which could be a starting point for future research and development in this field.

We realize that the article does not identify the gaps in previous research, which could be a starting point for future research and development in this field.

However, in our humble estimation, the publication of this review will have a significant impact on clinical practice by promoting early diagnosis, encouraging physicians to monitor patients for eating disorders and diabetes, and fostering interdisciplinary collaboration. The implementation of these changes in health care can have a significant impact on the quality of life of patients.

Author Contributions

Conceptualization, methodology, project administration: I.P.-C., writing: M.D., B.B. and M.H., review and editing: I.P.-C. and M.H. All authors have read and agreed to the published version of the manuscript.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

Funding Statement

This research received no external funding.

Footnotes

Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

References

Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

Not applicable.

Articles from Nutrients are provided here courtesy of Multidisciplinary Digital Publishing Institute (MDPI)

# data[].attributes.attachment_link.title
Eating Disorders and Diabetes: Facing the Dual Challenge

# data[].attributes.attachment_link.description
Eating disorders and diabetes mellitus are distinct yet closely linked health conditions, presenting distinct challenges in terms of care and management. Eating disorders encompass a spectrum of mental health disorders characterized by abnormal ...

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Diabetes distress is a state of emotional strain and worry specifically related to living with and managing diabetes. It's a common experience for many people with diabetes, characterized by feelings of frustration, discouragement, and being overwhelmed by the constant demands of self-care. A therapist or psychologist can help treat these symptoms

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The effectiveness of psychological interventions on diabetes distress and glycemic level in adults with type 2 diabetes: a systematic review and meta-analysis - BMC Psychiatry

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Aims The treatment of diabetes distress plays an important role in diabetes care; however, no meta-analysis has been performed to synthesize the short- and long-term effects of psychological interventions tailored for diabetes distress in people with type 2 diabetes. We aim to evaluate the evidence on tailored psychological interventions for diabetes distress as the primary outcome, focusing on individuals with type 2 diabetes. Methods Two reviewers independently searched eight databases from their inception to September 2024. EndNote X9 was used to screen records. The Revised Cochrane risk-of-bias tool for randomized trials was used to assess the risk of bias. The GRADE system was used to assess the overall certainty of the evidence. A random effect model was used to determine the mean difference or standardized mean difference with 95% CIs. Subgroup analyses based on several intervention characteristics and sensitivity analyses were also conducted. Results Totally, 22,279 records were yielded, and we finally included 18 studies in our systematic review. The meta-analysis included data from 16 studies representing 1639 participants. Interventions types included mindfulness-based and cognitive behavioral therapy, among others. Duration of interventions ranged from 4 weeks to 6 months. We found that psychological interventions that measured diabetes distress significantly reduced diabetes distress in the short-term in people with type 2 diabetes (SMD= -0.56; 95% CI= -0.90, -0.22; p = 0.001). Subgroup analysis indicated that this effect could be enhanced when delivered in a group format, by psychologist, using a technology component, or including participants having elevated baseline diabetes distress. However, the short- and long-term effects on HbA1c were non-significant, with results showing (MD = 0.02; 95% CI = -0.23 to 0.26; p = 0.89) and (MD = -0.27; 95% CI = -0.64 to 0.10; p = 0.15), respectively. The long-term effect on diabetes distress was also non-significant (SMD = -0.45; 95% CI = -0.93 to 0.03; p = 0.07). Conclusions Psychological interventions tailored for diabetes distress in people with type 2 diabetes are effective in reducing the level of diabetes distress immediately after the intervention. More trials are still needed to further enrich the evidence in this area.

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Occupational therapy plays a crucial role in helping individuals with diabetic retinopathy manage the impact of vision impairment on their daily lives. Occupational therapy focuses on helping individuals engage in meaningful activities and maintain their independence despite challenges like low vision. An occupational therapist helps with this.

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Cognitive rehabilitation for people with dementia and type 2 diabetes focuses on addressing cognitive impairments, particularly memory and attention, while also considering the impact of diabetes on cognitive function. Neuropsychologists They focus on the relationship between the brain and behavior and can offer assessments of brain function and psychological treatments.

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The role of cognitive rehabilitation in people with type 2 diabetes: A study protocol for a randomized controlled trial

# data[].attributes.attachment_link.description
Today, the prevalence of cognitive dysfunction and the prevalence of diabetes are increasing. Research shows that diabetes increases cognitive impairment risk, and cognitive impairment makes diabetes self-management more challenging. Diabetes…

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Type 2 diabetes can lead to hearing loss by damaging blood vessels and nerves in the inner ear, impacting how nerve signals travel from the ear to the brain. High blood glucose levels associated with diabetes can damage these delicate structures, resulting in a range of hearing difficulties. Audiologist and ENT doctors serve as providers to help with these issues.

# data[].attributes.body
A change in your diet or how you track your food can be helpful when dealing with Type 2. Portion control, counting carbs, and balancing when you eat and when you take your meds can all benefit you. For most people, this would probably be a 5 or 6 out of 10 on the difficulty scale but as they get more used to it, that curve should drop significantly. A nutritionist or dietician would be excellent in helping with these changes.

# data[].attributes.attachment_link.title
Diabetes management: How lifestyle, daily routine affect blood sugar

# data[].attributes.attachment_link.description
Know what makes your blood sugar level rise and fall so you can take charge of your condition.

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Lifestyles that include at least 150 minutes a week along with dietary goals have shown a reduction in the risk of developing type 2 diabetes by a margin of 40 to 70%. Insulin action in muscles can be modified by physical activity due to muscle glycogen repletion. even low intensity exercise for an hour can be beneficial to all adults trying to enhance their insulin action.

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The adoption and maintenance of physical activity are critical foci for blood glucose management and overall health in individuals with diabetes and prediabetes. Recommendations and precautions vary depending on individual characteristics and health status. In this Position Statement, we provide a clinically oriented review and evidence-based recommendations regarding physical activity and exercise in people with type 1 diabetes, type 2 diabetes, gestational diabetes mellitus, and prediabetes.

Physical activity includes all movement that increases energy use, whereas exercise is planned, structured physical activity. Exercise improves blood glucose control in type 2 diabetes, reduces cardiovascular risk factors, contributes to weight loss, and improves well-being ( 1, 2). Regular exercise may prevent or delay type 2 diabetes development ( 3). Regular exercise also has considerable health benefits for people with type 1 diabetes (e.g., improved cardiovascular fitness, muscle strength, insulin sensitivity, etc.) ( 4). The challenges related to blood glucose management vary with diabetes type, activity type, and presence of diabetes-related complications ( 5, 6). Physical activity and exercise recommendations, therefore, should be tailored to meet the specific needs of each individual.

TYPES AND CLASSIFICATIONS OF DIABETES AND PREDIABETES

Physical activity recommendations and precautions may vary by diabetes type. The primary types of diabetes are type 1 and type 2. Type 1 diabetes (5%-10% of cases) results from cellular-mediated autoimmune destruction of the pancreatic β-cells, producing insulin deficiency ( 7). Although it can occur at any age, β-cell destruction rates vary, typically occurring more rapidly in youth than in adults. Type 2 diabetes (90%-95% of cases) results from a progressive loss of insulin secretion, usually also with insulin resistance. Gestational diabetes mellitus occurs during pregnancy, with screening typically occurring at 24-28 weeks of gestation in pregnant women not previously known to have diabetes. Prediabetes is diagnosed when blood glucose levels are above the normal range but not high enough to be classified as diabetes; affected individuals have a heightened risk of developing type 2 diabetes ( 7) but may prevent/delay its onset with physical activity and other lifestyle changes ( 8).

TYPES OF EXERCISE AND PHYSICAL ACTIVITY

Aerobic exercise involves repeated and continuous movement of large muscle groups ( 9). Activities such as walking, cycling, jogging, and swimming rely primarily on aerobic energy-producing systems. Resistance (strength) training includes exercises with free weights, weight machines, body weight, or elastic resistance bands. Flexibility exercises improve range of motion around joints ( 10). Balance exercises benefit gait and prevent falls ( 11). Activities like tai chi and yoga combine flexibility, balance, and resistance activities.

BENEFITS OF EXERCISE AND PHYSICAL ACTIVITY

Aerobic Exercise Benefits

Aerobic training increases mitochondrial density, insulin sensitivity, oxidative enzymes, compliance and reactivity of blood vessels, lung function, immune function, and cardiac output ( 12). Moderate to high volumes of aerobic activity are associated with substantially lower cardiovascular and overall mortality risks in both type 1 and type 2 diabetes ( 13). In type 1 diabetes, aerobic training increases cardiorespiratory fitness, decreases insulin resistance, and improves lipid levels and endothelial function ( 14). In individuals with type 2 diabetes, regular training reduces A1C, triglycerides, blood pressure, and insulin resistance ( 15). Alternatively, high-intensity interval training (HIIT) promotes rapid enhancement of skeletal muscle oxidative capacity, insulin sensitivity, and glycemic control in adults with type 2 diabetes ( 16, 17) and can be performed without deterioration in glycemic control in type 1 diabetes ( 18, 19).

Resistance Exercise Benefits

Benefits of Other Types of Physical Activity

Flexibility and balance exercises are likely important for older adults with diabetes. Limited joint mobility is frequently present, resulting in part from the formation of advanced glycation end products, which accumulate during normal aging and are accelerated by hyperglycemia ( 25). Stretching increases range of motion around joints and flexibility ( 10) but does not affect glycemic control. Balance training can reduce falls risk by improving balance and gait, even when peripheral neuropathy is present ( 11). Group exercise interventions (resistance and balance training, tai chi classes) may reduce falls by 28%−29% ( 26). The benefits of alternative training like yoga and tai chi are less established, although yoga may promote improvement in glycemic control, lipid levels, and body composition in adults with type 2 diabetes ( 27). Tai chi training may improve glycemic control, balance, neuropathic symptoms, and some dimensions of quality of life in adults with diabetes and neuropathy, although high-quality studies on this training are lacking ( 28).

BENEFITS OF AND RECOMMENDATIONS FOR REDUCED SEDENTARY TIME

All adults, and particularly those with type 2 diabetes, should decrease the amount of time spent in daily sedentary behavior. B

Prolonged sitting should be interrupted with bouts of light activity every 30 min for blood glucose benefits, at least in adults with type 2 diabetes. C

The above two recommendations are additional to, and not a replacement for, increased structured exercise and incidental movement. C

PHYSICAL ACTIVITY AND TYPE 2 DIABETES

Daily exercise, or at least not allowing more than 2 days to elapse between exercise sessions, is recommended to enhance insulin action. B

Adults with type 2 diabetes should ideally perform both aerobic and resistance exercise training for optimal glycemic and health outcomes. C

Children and adolescents with type 2 diabetes should be encouraged to meet the same physical activity goals set for youth in general. C

Structured lifestyle interventions that include at least 150 min/week of physical activity and dietary changes resulting in weight loss of 5%-7% are recommended to prevent or delay the onset of type 2 diabetes in populations at high risk and with prediabetes. A

Insulin Action and Physical Activity

Insulin action in muscle and liver can be modified by acute bouts of exercise and by regular physical activity ( 47). Acutely, aerobic exercise increases muscle glucose uptake up to fivefold through insulin-independent mechanisms. After exercise, glucose uptake remains elevated by insulin-independent (∼2 h) and insulin-dependent (up to 48 h) mechanisms if exercise is prolonged ( 48), which is linked with muscle glycogen repletion ( 49, 50). Improvements in insulin action may last for 24 h following shorter duration activities (∼20 min) if the intensity is elevated to near-maximal effort intermittently ( 51, 52). Even low-intensity aerobic exercise lasting ≥60 min enhances insulin action in obese, insulin-resistant adults for at least 24 h ( 53). If enhanced insulin action is a primary goal, then daily moderate- or high-intensity exercise is likely optimal ( 54).

Regular training increases muscle capillary density, oxidative capacity, lipid metabolism, and insulin signaling proteins ( 47), which are all reversible with detraining ( 55). Both aerobic and resistance training promote adaptations in skeletal muscle, adipose tissue, and liver associated with enhanced insulin action, even without weight loss ( 56, 57). Regular aerobic training increases muscle insulin sensitivity in individuals with prediabetes ( 58) and type 2 diabetes ( 59) in proportion to exercise volume ( 60). Even low-volume training (expending just 400 kcal/week) improves insulin action in previously sedentary adults ( 60). Those with higher baseline insulin resistance have the largest improvements, and a dose response is observed up to about 2,500 kcal/week ( 60). Resistance training enhances insulin action similarly ( 56), as do HIIT and other modes ( 2, 15- 17). Combining endurance exercise with resistance exercise may provide greater improvements ( 61), and HIIT may be superior to continuous aerobic training in adults with diabetes ( 16).

Physical Activity in Adults With Type 2 Diabetes

The Look AHEAD (Action for Health in Diabetes) trial ( 62) was the largest randomized trial evaluating a lifestyle intervention in older adults with type 2 diabetes compared with a diabetes support and education control group. The intensive lifestyle intervention group targeted weight loss of at least 7% through a modest dietary energy deficit and at least 175 min/week of unsupervised exercise. Major cardiovascular events were the same in both groups, possibly in part due to greater use of cardioprotective medications in the diabetes support and education group ( 62). However, as reviewed by Pi-Sunyer ( 63), the intensive lifestyle intervention group achieved significantly greater sustained improvements in weight loss, cardiorespiratory fitness, blood glucose control, blood pressure, and lipids with fewer medications; less sleep apnea, severe diabetic kidney disease and retinopathy, depression, sexual dysfunction, urinary incontinence, and knee pain; and better physical mobility maintenance and quality of life, with lower overall health care costs. This trial provided very strong evidence of profound health benefits from intensive lifestyle intervention. Moreover, aerobic exercise clearly improves glycemic control in type 2 diabetes, particularly when at least 150 min/week are undertaken ( 64). Resistance exercise (free weights or weight machines) increases strength in adults with type 2 diabetes by about 50% ( 24) and improves A1C by 0.57% ( 64). A meta-analysis of 12 trials in adults with type 2 diabetes reported a greater reduction (difference of −0.18%) in A1C following aerobic compared with resistance training but no difference in cardiovascular risk marker reduction ( 65). For glycemic control, combined training is superior to either type of training undertaken alone ( 61, 66). Therefore, adults with type 2 diabetes should ideally perform both aerobic and resistance exercise training for optimal glycemic and health outcomes.

Physical Activity in Youth With Type 2 Diabetes

Randomized trials evaluating exercise interventions in youth with type 2 diabetes are limited and inconclusive, although benefits are likely similar to those in adults. In the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study ( 67), youth aged 10-17 years with type 2 diabetes were stabilized on metformin and then randomized to metformin plus placebo, metformin plus rosiglitazone, or metformin plus lifestyle intervention and followed for a mean of 3.86 years. The lifestyle intervention included modest weight loss achieved through dietary energy restriction and increased physical activity (minimum 200 min/week of moderate to vigorous activity for most; >300 min/week for already active youth), along with metformin use. The rate of glycemic failure (A1C >8.0% or need to initiate insulin) was not significantly reduced in the lifestyle plus metformin group compared with metformin only or metformin plus rosiglitazone. Given the limited data in youth with type 2 diabetes, it is recommended that children and adolescents with type 2 diabetes meet the same physical activity goals set for youth in general ( http://www.cdc.gov/physicalactivity/basics/children): a minimum 60 min/day of moderate-to-vigorous physical activity, including strength-related exercise at least 3 days/week.

Prevention and Treatment of Type 2 Diabetes With Lifestyle Intervention

Structured lifestyle intervention trials that include physical activity at least 150-175 min/week and dietary energy restriction targeting weight loss of 5%−7% have demonstrated reductions of 40%-70% in the risk of developing type 2 diabetes in people with impaired glucose tolerance ( 66). A recent systematic review of 53 studies (30 of diet and physical activity promotion programs vs. usual care, 13 of more intensive vs. less intensive programs, and 13 of single programs) that evaluated 66 lifestyle intervention programs reported that, compared with usual care, diet and physical activity promotion programs reduced type 2 diabetes incidence, body weight, and fasting blood glucose while improving other cardiometabolic risk factors ( 68). Trials evaluating less resource-intensive lifestyle interventions have also shown effectiveness ( 3), and adherence to guidelines is associated with a greater weight loss ( 69).

PHYSICAL ACTIVITY AND TYPE 1 DIABETES

Youth and adults with type 1 diabetes can benefit from being physically active, and activity should be recommended to all. B

Blood glucose responses to physical activity in all people with type 1 diabetes are highly variable based on activity type/timing and require different adjustments. B

Additional carbohydrate intake and/or insulin reductions are typically required to maintain glycemic balance during and after physical activity. Frequent blood glucose checks are required to implement carbohydrate intake and insulin dose adjustment strategies. B

Insulin users can exercise using either basal-bolus injection regimens or insulin pumps, but there are advantages and disadvantages to both insulin delivery methods. C

Continuous glucose monitoring during physical activity can be used to detect hypoglycemia when used as an adjunct rather than in place of capillary glucose tests. C

Physical Activity and Sports in Youth and Adults With Type 1 Diabetes

Youth experience many health benefits from physical activity participation ( 9). A meta-analysis of 10 trials in youth <18 years of age with type 1 diabetes found significant improvements in A1C in exercisers ( 70), and exercising more than three sessions/week for longer (>1 h/session) and doing both aerobic and resistance exercise may be beneficial ( 70). In adults, regular physical activity has been associated with decreased mortality ( 71). There is insufficient evidence on the ideal type, timing, intensity, and duration of exercise for optimal glycemic control.

Effects of Activity Type and Timing on Glycemic Balance

Blood glucose responses to physical activity in type 1 diabetes are highly variable ( 72). In general, aerobic exercise decreases blood glucose levels if performed during postprandial periods with the usual insulin dose administered at the meal before exercise ( 73), and prolonged activity done then may cause exaggerated decreases ( 74- 76). Exercise while fasting may produce a lesser decrease or a small increase in blood glucose ( 77). Very intense activities may provide better glucose stability ( 22) or a rise in blood glucose if the relative intensity is high and done for a brief duration (≤10 min) ( 78). Mixed activities, such as interval training or team/individual field sports, are associated with better glucose stability than those that are predominantly aerobic ( 18, 79- 82), although variable results have been reported for intermittent, high-intensity exercise ( 80).

Management of Food and Insulin With Physical Activity

Variable glycemic responses to physical activity ( 72) make uniform recommendations for management of food intake and insulin dosing difficult. To prevent hypoglycemia during prolonged (≥30 min), predominantly aerobic exercise, additional carbohydrate intake and/or reductions in insulin are typically required. For low- to moderate-intensity aerobic activities lasting 30−60 min undertaken when circulating insulin levels are low (i.e., fasting or basal conditions), ∼10−15 g of carbohydrate may prevent hypoglycemia ( 83). For activities performed with relative hyperinsulinemia (after bolus insulin), 30−60 g of carbohydrate per hour of exercise may be needed ( 84), which is similar to carbohydrate requirements to optimize performance in athletes with ( 85) or without ( 86) type 1 diabetes.

As recommended in Table 1, blood glucose concentrations should always be checked prior to exercise undertaken by individuals with type 1 diabetes. The target range for blood glucose prior to exercise should ideally be between 90 and 250 mg/dL (5.0 and 13.9 mmol/L). Carbohydrate intake required will vary with insulin regimens, timing of exercise, type of activity, and more ( 87), but it will also depend on starting blood glucose levels. As an alternative or a complement to carbohydrate intake, reductions in basal and/or bolus insulin dose should be considered for exercise-induced hypoglycemia prevention; lowering insulin levels adequately during activity may reduce or eliminate the need for carbohydrate intake. For example, a 20% reduction in basal insulin for individuals on multiple daily injections (MDI) can be made for doses both before and after exercise, but this strategy may not fully attenuate the decline in glucose during the activity ( 89). Continuous subcutaneous insulin infusion (CSII) users can reduce ( 90) or suspend ( 91) insulin delivery at the start of exercise, but this strategy does not always prevent hypoglycemia ( 91, 92). Performing basal rate reductions 30−60 min before exercise may reduce hypoglycemia due to pharmacokinetics of rapid-acting insulin analogs used in CSII ( 93). For exercise performed within 2−3 h after bolus insulin via CSII or MDI, 25%−75% reductions in insulin may limit hypoglycemia ( Table 2). Frequent blood glucose checks are required when implementing insulin and carbohydrate adjustments.

Use of CSII and MDI for Activity

Individuals using CSII or MDI as a basal-bolus regimen can exercise with few restrictions. CSII offers some advantages over MDI due to greater flexibility in basal rate adjustments and limiting postexercise hyperglycemia ( 98), with some limitations. For example, aerobic exercise may accelerate basal insulin absorption from the subcutaneous depot ( 74), whereas basal insulin glargine absorption is largely unaffected ( 99). Skin irritation, pump tubing, and wearing a pump that is visible to others can be concerns ( 100). In certain sports, such as basketball or contact sports, wearing pumps and other devices may be prohibited during competition. Frustration with CSII devices and exercise may lead to discontinuation of pump therapy ( 100).

Use of Continuous Glucose Monitoring With Activity

Continuous glucose monitoring (CGM) may decrease the fear of exercise-induced hypoglycemia in type 1 diabetes by providing blood glucose trends that allow users to prevent and treat hypoglycemia sooner ( 83). Although a few studies have found acceptable CGM accuracy during exercise ( 101- 104), others have reported inadequate accuracy ( 105) and other problems, such as sensor filament breakage ( 103, 104), inability to calibrate ( 102), and time lags between the change in blood glucose and its detection by CGM ( 106). Differences in sensor performance have also been noted ( 107- 109). Although it is a potentially useful tool during and after exercise ( 110), CGM values have traditionally required confirmation by finger-stick glucose testing prior to making regimen changes, but approval of nonadjunctive use is likely forthcoming in the near future.

RECOMMENDED PHYSICAL ACTIVITY PARTICIPATION FOR PEOPLE WITH DIABETES

Pre-exercise medical clearance is generally unnecessary for asymptomatic individuals prior to beginning low- or moderate-intensity physical activity not exceeding the demands of brisk walking or everyday living. B

Most adults with diabetes should engage in 150 min or more of moderate-to-vigorous intensity activity weekly, spread over at least 3 days/week, with no more than 2 consecutive days without activity. Shorter durations (minimum 75 min/week) of vigorous-intensity or interval training may be sufficient for younger and more physically fit individuals. B for type 2 diabetes, C for type 1 diabetes

Children and adolescents with type 1 or type 2 diabetes should engage in 60 min/day or more of moderate or vigorous intensity aerobic activity, with vigorous, muscle-strengthening, and bone-strengthening activities included at least 3 days/week. C

Adults with diabetes should engage in 2-3 sessions/week of resistance exercise on nonconsecutive days. B for type 2 diabetes, C for type 1 diabetes

Flexibility training and balance training are recommended 2-3 times/week for older adults with diabetes. Yoga and tai chi may be included based on individual preferences to increase flexibility, muscular strength, and balance. C

Individuals with diabetes or prediabetes are encouraged to increase their total daily incidental (nonexercise) physical activity to gain additional health benefits. C

To gain more health benefits from physical activity programs, participation in supervised training is recommended over nonsupervised programs. B

Pre-exercise Health Screening and Evaluation

The American College of Sports Medicine (ACSM) recently proposed a new model for exercise preparticipation health screening on the basis of 1) the individual's current physical activity levels; 2) the presence of signs or symptoms and/or known cardiovascular, metabolic, or renal disease; and 3) the desired exercise intensity, all of which are risk modulators of exercise-related cardiovascular events ( 111). The ACSM no longer includes risk factor assessment in the exercise preparticipation health screening process. However, their recommendation is that anyone with diabetes who is currently sedentary and desires to begin physical activity at any intensity (even low intensity) should obtain prior medical clearance from a health care professional ( 111). We believe this recommendation is excessively conservative.

Physical activity does carry some potential health risks for people with diabetes, including acute complications like cardiac events, hypoglycemia, and hyperglycemia. In low- and moderate-intensity activity undertaken by adults with type 2 diabetes, the risk of exercise-induced adverse events is low. In individuals with type 1 diabetes (any age) the only common exercise-induced adverse event is hypoglycemia. No current evidence suggests that any screening protocol beyond usual diabetes care reduces risk of exercise-induced adverse events in asymptomatic individuals with diabetes ( 112, 113). Thus, pre-exercise medical clearance is not necessary for asymptomatic individuals receiving diabetes care consistent with guidelines who wish to begin low- or moderate-intensity physical activity not exceeding the demands of brisk walking or everyday living.

However, some individuals who plan to increase their exercise intensity or who meet certain higher-risk criteria may benefit from referral to a health care provider for a checkup and possible exercise stress test before starting such activities ( 6). In addition, most adults with diabetes may also benefit from working with a diabetes-knowledgeable exercise physiologist or certified fitness professional to assist them in formulating a safe and effective exercise prescription. A combination of careful consideration of multiple factors and sound clinical judgment based on the individual's medical history and physical examination will determine their degree of risk of acute complications and identify the most appropriate physical activities to avoid or limit.

Aerobic Exercise Training

Youth with type 1 or type 2 diabetes should follow general recommendations for children and adolescents. These include 60 min/day or more of moderate- or vigorous-intensity aerobic activity, with vigorous, muscle-strengthening, and bone-strengthening activities at least 3 days/week ( 9).

Resistance Exercise Training

Flexibility, Balance, and Other Training

Daily Movement

Increasing unstructured physical activity (e.g., errands, household tasks, dog walking, or gardening) increases daily energy expenditure and assists with weight management ( 119- 121). Unstructured activity also reduces total daily sitting time. Increasing nonexercise activity, even in brief (3−15 min) bouts, is effective in acutely reducing postprandial hyperglycemia and improving glycemic control in those with prediabetes and type 1 and type 2 diabetes, most prominently after meals ( 41, 43- 46, 75, 122- 124). Increasing unstructured physical activity should be encouraged as part of a whole-day approach, or at least initially as a stepping stone for individuals who are sedentary and unable/reluctant to participate in more structured exercise.

Supervised Versus Nonsupervised Training

Supervised aerobic or resistance training reduces A1C in adults with type 2 diabetes whether or not they include dietary cointervention, but unsupervised exercise only reduces A1C with a concomitant dietary intervention ( 64). Similarly, individuals undertaking supervised aerobic and resistance exercise achieve greater improvements in A1C, BMI, waist circumference, blood pressure, fitness, muscular strength, and HDL cholesterol ( 125). Thus, supervised training is recommended when feasible, at least for adults with type 2 diabetes.

PHYSICAL ACTIVITY AND PREGNANCY WITH DIABETES

Women with preexisting diabetes of any type should be advised to engage in regular physical activity prior to and during pregnancy. C

Pregnant women with or at risk for gestational diabetes mellitus should be advised to engage in 20-30 min of moderate-intensity exercise on most or all days of the week. B

MINIMIZING EXERCISE-RELATED ADVERSE EVENTS IN PEOPLE WITH DIABETES

Insulin regimen and carbohydrate intake changes should be used to prevent exercise-related hypoglycemia. Other strategies involve including short sprints, performing resistance exercise before aerobic exercise in the same session, and activity timing. B

Risk of nocturnal hypoglycemia following physical activity may be mitigated with reductions in basal insulin doses, inclusion of bedtime snacks, and/or use of continuous glucose monitoring. C

Exercise-induced hyperglycemia is more common in type 1 diabetes but may be modulated with insulin administration or a lower-intensity aerobic cooldown. Exercising with hyperglycemia and elevated blood ketones is not recommended. C

Some medications besides insulin may increase the risks of exercise-related hypoglycemia and doses may need to be adjusted based on exercise training. C

Older adults with diabetes or anyone with autonomic neuropathy, cardiovascular complications, or pulmonary disease should avoid exercising outdoors on very hot and/or humid days to prevent heat-related illnesses. C

Exercise training should progress appropriately to minimize risk of injury. C

Hypoglycemia

Hyperglycemia

Very intense exercise such as sprinting ( 134), brief but intense aerobic exercise ( 145), and heavy powerlifting ( 146, 147) may promote hyperglycemia, especially if starting blood glucose levels are elevated ( 145). Hyperglycemia risk is mitigated if intense activities are interspersed between moderate-intensity aerobic ones ( 82, 148). Similarly, combining resistance training (done first) with aerobic training (second) optimizes glucose stability in type 1 diabetes ( 23). To correct postexercise hyperglycemia, a conservative (50% of usual) correction can be administered ( 77) or an aerobic cooldown may be done to lower it (I.S. Millán, personal communication). Excessive insulin corrections after exercise increase nocturnal hypoglycemia risk, which can result in mortality ( 149).

Individuals with type 1 diabetes should test for blood ketones if they have unexplained hyperglycemia (≥250 mg/dL). Exercise should be postponed or suspended if blood ketone levels are elevated (≥1.5 mmol/L), as blood glucose levels and ketones may rise further with even mild activity.

Medication Effects

Heat-Related Illness During Physical Activity

Physical activity increases bodily heat production and core temperature, leading to greater skin blood flow and sweating. In relatively young adults with type 1 diabetes, temperature regulation is only impaired during high-intensity exercise ( 152, 153). With increasing age, poor blood glucose control, and neuropathy, skin blood flow and sweating may be impaired in adults with type 1 ( 152, 154) and type 2 ( 155) diabetes, increasing the risk of heat-related illness. Chronic hyperglycemia also increases risk through dehydration caused by osmotic diuresis, and some medications that lower blood pressure may also impact hydration and electrolyte balance. Older adults with diabetes or anyone with autonomic neuropathy, cardiovascular complications, or pulmonary disease should avoid exercising outdoors on very hot and/or humid days.

Orthopedic and Overuse Injuries

MANAGING PHYSICAL ACTIVITY WITH HEALTH COMPLICATIONS

Physical activity with vascular diseases can be undertaken safely but with appropriate precautions. B

Physical activity done with peripheral neuropathy necessitates proper foot care to prevent, detect, and prevent problems early to avoid ulceration and amputation. B

The presence of autonomic neuropathy may complicate being active; certain precautions are warranted to prevent problems during activity. C

Vigorous aerobic or resistance exercise; jumping, jarring, head-down activities; and breath holding should be avoided in anyone with severe nonproliferative and unstable proliferative diabetic retinopathy. E

Exercise does not accelerate progression of kidney disease and can be undertaken safely, even during dialysis sessions. C

Regular stretching and appropriate progression of activities should be done to manage joint changes and diabetes-related orthopedic limitations. C

PROMOTING THE ADOPTION AND MAINTENANCE OF PHYSICAL ACTIVITY

Targeted behavior-change strategies should be used to increase physical activity in adults with type 2 diabetes. B

When using step counters, adults with type 2 diabetes should initially set tolerable targets for steps/day before progressing toward higher goals. C

For adults with type 2 diabetes, Internet-delivered interventions for physical activity promotion may be used to improve outcomes. C

Behavior-Change Strategies

Behavioral interventions can significantly increase physical activity in adults with type 2 diabetes ( 173), and A1C reductions produced by such interventions have been sustained to 24 months ( 174). Five key techniques have been identified: 1) prompt focus on past success, 2) barrier identification/problem-solving, 3) use of follow-up prompts, 4) provision of information on where/when to perform the behavior, and 5) prompt review of behavioral goals ( 175). However, motivational interviewing is not significantly better than usual care ( 176), and other intervention factors associated with weight loss, such as number and duration of contacts, have been inconsistent or not associated with greater participation ( 177).

Technology-Based Strategies

Conclusions

Physical activity and exercise should be recommended and prescribed to all individuals with diabetes as part of management of glycemic control and overall health. Specific recommendations and precautions will vary by the type of diabetes, age, activity done, and presence of diabetes-related health complications. Recommendations should be tailored to meet the specific needs of each individual. In addition to engaging in regular physical activity, all adults should be encouraged to decrease the total amount of daily sedentary time and to break up sitting time with frequent bouts of activity. Finally, behavior-change strategies can be used to promote the adoption and maintenance of lifetime physical activity.

Article Information

Duality of Interest. No potential conflicts of interest relevant to this article were reported.

References

9. Physical Activity Guidelines Advisory Committee Physical Activity Guidelines Advisory Committee Report. Washington, DC, U.S. Department of Health and Human Services, 2008, p. 683 [Google Scholar]

115. Mitranun W, Deerochanawong C, Tanaka H, Suksom D Continuous vs interval training on glycemic control and macro- and microvascular reactivity in type 2 diabetic patients. Scand J Med Sci Sports 2014;24:e69-e76 [DOI] [PubMed]

179. Tudor-Locke C, Craig CL, Brown WJ, et al. How many steps/day are enough? For adults. Int J Behav Nutr Phys Act 2011;8:7921798015 [Google Scholar]

Articles from Diabetes Care are provided here courtesy of American Diabetes Association

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Physical Activity/Exercise and Diabetes: A Position Statement of the American Diabetes Association

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The adoption and maintenance of physical activity are critical foci for blood glucose management and overall health in individuals with diabetes and prediabetes. Recommendations and precautions vary depending on individual characteristics and health status. In this Position Statement, we provide a clinically oriented review and evidence-based recommendations regarding physical activity and exercise in people with type 1 diabetes, type 2 diabetes, gestational diabetes mellitus, and prediabetes.

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Type 2 diabetes disproportionately affects minority populations. The reasons include personal, social, economic, and environmental factors that all contribute to a greater health risk. One challenge is we need more specific legislation or education on the subject that are tailored to these areas with differing reasons leading to the higher health risks.

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Verifying you are human. This may take a few seconds.

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To help reduce the risk of type 2 diabetes, you can focus on maintaining a healthy lifestyle through exercise. This could include walks each day or weight training or even a sport. Staying active can keep you healthier and stave off disease. It also keeps your brain healthy as well. One barrier to this is not everybody is capable of exercising or they don't know where to start. A personal trainer can help tailor a plan specifically to you so you can still remain healthy.

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Take Steps to Prevent Type 2 Diabetes - MyHealthfinder | odphp.health.gov

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Diabetes is one of the leading causes of disability and death in the United States. If it’s not controlled, diabetes can cause serious health problems, like blindness, nerve damage, and kidney disease. The good news is that you can do a lot to prevent type 2 diabetes, including eating healthy and staying active.

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Two technologies that can help you treat/live with your type two are Continuous Glucose Monitors and Insulin Pumps. CGMs will constantly monitor your blood sugar levels to keep you updated if they need to be raised or lowered. Insulin pumps will continually or periodically pump insulin into your system so you don't have to run the risk of forgetting all the time. One drawback of the insulin pump is it has to be attached to your body at all times and that can be cumbersome to some people.

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From insulin pumps to glucose meters, explore our comprehensive breakdown of the choices when it comes to diabetes technology.

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A couple public health interventions that help the public reduce their risk of type 2 are Awareness Campaigns from the ADA and AMA as well as an affordable evidence-based lifestyle change program offer by the National Diabetes Prevention Program. The program is directed at the individual and more than 750,000 adults have participated since March 2024. For the awareness campaign, this is aimed at the overall public to increase awareness. The biggest barrier, that the campaign aims to correct, is the awareness of how you can start anytime to work toward reducing your risks and living a healthier lifestyle.

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National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP)

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Health and Economic Benefits of Diabetes Interventions

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Healthy choices and good diabetes management can reduce cases, complications, and associated costs.

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Type 2 diabetes and low income communities

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Type 2 diabetes and low income communities

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Low income communities are affect by diabetes in two ways. By not having the funds or access to healthier food options and other things that are not accessible they develop Type 2 diabetes. Also, after being diagnosed with type 2 diabetes a challenge that for low income families to have access to the healthcare they need in order to treat it.

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Competing Interests: The authors have declared that no competing interests exist. ✉* E-mail: ppz4cdc.gov

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Income-related inequalities in diagnosed diabetes prevalence among US adults, 2001−2018

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The overall prevalence of diabetes has increased over the past two decades in the United States, disproportionately affecting low-income populations. We aimed to examine the trends in income-related inequalities in diabetes prevalence and to…

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To help reduce the risk or reverse the affects of type 2 diabetes adapting and maintaining a healthy diet will be beneficial. Exchanging fruits and vegetables for the sugary foods are small steps to achieving the results. One obstacle is that often healthier food options are hard to come by in low income areas as the focus is on quick fixes and snacks instead of fresh fruits and vegetables.

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Patient education: Type 2 diabetes and diet (Beyond the Basics) - UpToDate

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Two public health prevetions for type 2 diabetes.

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Two public health prevetions for type 2 diabetes.

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The Diabetes Self-Management Education and Support (DSMES) services help people with diabetes effectively manage their condition and prevent complications. Another public health interventions the National Institute of Health provides nutritional counseling Nutrition counseling that works toward improving or maintaining glycemic targets, achieving weight management goals, and improving cardiovascular risk factors (e.g., blood pressure, lipids, etc.) within individualized treatment goals is recommended for all adults with diabetes and prediabetes.

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Public Health Approaches to Type 2 Diabetes Prevention: the US National Diabetes Prevention Program and Beyond

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This article highlights foundational evidence, translation studies, and current research behind type 2 diabetes prevention efforts worldwide, with focus on high-risk populations, and whole-population approaches as catalysts to global prevention.…

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Blood Glucose Meters and Smart Insulin Pens

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Blood Glucose Meters and Smart Insulin Pens

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Blood glucose meters are small portable devices that come with test strips that you apply small drops of blood to, and the device will display blood sugar in seconds. A second device that is an advancement in diabetic tools and equipment is the Smart Insulin Pen that will calculate your dose of insulin based on your blood glucose level. These technologies create convenience for people with diabetes and help them manage their blood sugar accurately and can include alerts and updates for the user.

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Whether it be a continuous glucose monitor (CGM), insulin pump, insulin pen, blood glucose (blood sugar) monitor, or other diabetes technology, they've become an essential part of diabetes management.

These tools have helped millions with diabetes improve their blood glucose levels and may help prevent or delay long-term complications over time. But with so many options to choose from, at times it may seem overwhelming.

Before your next health care appointment, read our guide to prepare for the discussion with your health care providers about what diabetes device(s) may be best for you, your lifestyle, and medical history.

Types of Devices and What They Do

Check out the different types of diabetes devices and how they might benefit you:

Continuous Glucose Monitors (CGMs)

CGMs do what the name says, they continuously monitor your blood glucose (blood sugar) by providing real-time updates throughout the day and alert you when your levels become too high or too low. A tiny sensor, about a half-inch long, is inserted just below your skin, usually on your belly or arm. From there, an electrode measures your glucose levels within the tissue fluid rather than directly from your blood, almost entirely replacing the need for finger pricks-which is a huge relief for many.

Some varieties of CGMs connect via Bluetooth to your smartphone or laptop so you can easily analyze your blood glucose trends. This is reported to the user so they can see the trends past blood glucose, where they currently are, and show trends arrows to see what direction their blood glucose is headed. And, it can transmit these data-plus the alerts when your levels get too high or low-to other people in your life (health care provider, loved one, etc.) who will benefit from this information and can help you in case of an episode of hypo or hyperglycemia (low and high blood glucose).
Check out our Consumer Guide to browse different brands and models of CGMs.
Insulin Pump

An insulin pump, an external device that is attached to your body, works by mimicking the insulin release of a body similar to someone without diabetes. They can be programmed to release whichever insulin you usually use at the rate that's determined best for you-whether that's a steady, continuous release throughout the day or a surge release, such as in response to food.

You still have to monitor your blood glucose (blood sugar) while using an insulin pump, but it does minimize the need for insulin injections.

While setting up and attaching the pump can get some getting used to, the insulin pump can be a great alternative for people who need multiple injections on a daily basis.
Check out our Consumer Guide to browse different brands and models of insulin pumps.
Connected CGM and Insulin Pump

It's the best of both worlds! Some CGM devices can now be incorporated with insulin pumps to adjust insulin delivery to decrease hypo and hyperglycemia as well as to increase time in range (the percent of time that your blood glucose levels are in your recommended target range). This connected system provides the continuous glucose checks of the CGM with the automatic insulin delivery of the pump. Though you will still need to administer insulin to match your carbohydrate intake.
Check out our Consumer Guide to browse different brands and models of connected CGMs and insulin pumps.
Blood Glucose Meters

This device is considered to be one of the more standard diabetes devices. It's a small, portable device with a screen that comes with test strips that are designed to use with the meter. You prick your finger with a lancet device, apply the small drop of blood to the test strip, and your blood glucose (blood sugar) reading is displayed in a matter of seconds on the display.

Some brands come with more bells and whistles that allow you to download data on a computer, in addition to other functions, while some are more basic but still get the job done.
Check out our Consumer Guide to browse different brands and models of blood glucose meters.
Smart Insulin Pens

A smart insulin pen is the tech-savvy sibling to the insulin pen. Insulin pens allow you to dial in the correct dose of insulin, but smart insulin pens take it a step further by calculating your dose of insulin based on your blood glucose level and carbohydrate intake. The smart insulin pen will also help you determine correction doses, keep track of recent doses, and provide alerts when you need to administer more insulin.

They're able to do this through sharing data via Bluetooth to an app you can download to your smartphone. It uses data from the last time you ate a meal, how much insulin you currently have in your body, blood glucose (blood sugar) history, and more to make these decisions.
Check out our Consumer Guide to browse different brands and models of smart insulin pens.
Insurance Coverage of Diabetes Technology

Insurance coverage of each of these devices varies from company to company. Some questions they may ask to decide if the device warrants coverage are:

How necessary is the device to your diabetes management?

How much does it cost?

What model of the device are you interested in?

Has your doctor prescribed it?

How necessary is the device to your diabetes management?

While some technologies, like a blood glucose meter, are widely considered to be essential, others like CGMs are considered non-essential. You'll will want to discuss the advantages of using a device in order to properly manage your diabetes with your health care provider. Also, keep in mind that the device may have certain qualifications by the insurer for coverage.

How much does it cost?

When browsing for products as a consumer, price is often a big factor in your decision making. And the same goes for your insurance company-they often only provide coverage for technology at certain price point. Do your homework to determine what devices are covered.

What model of the device are you interested in?

Let's say your insurance provider approves the coverage of an insulin pump. You find one you really like that has lots of great features-but the company denies it because it is not on the list of approved devices by the company for coverage. So, while your provider may provide coverage for an insulin pump, they don't necessarily provide coverage for every insulin pump.

Has your doctor prescribed it?

In order for your insurer to entertain the idea of providing coverage of diabetes device, your health care provider has to first give you a prescription for it.

How to Make the Decision

The decision for which type of diabetes technology is best for you should be made jointly with your health care and insurance providers.

You and your health care provider should consider a few things when deciding which device is best for you:

Your medical history

Your diabetes history

Your lifestyle

Your diabetes pain points (what you struggle with the most)

What you want out of a device

Your insurance provider will be able to work with you to determine coverage, what is needed for approval, and what model of the device you are approved for.

Also, be sure to ask for an appointment with a diabetes care and education specialist-one with experience in diabetes technology-to be properly trained on how to use the device.

Keep in mind, the world of technology is ever changing in diabetes care, so stay up to date by asking questions of your health care team to help you take advantage of the best options for you and your diabetes.

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Whether it be a continuous glucose monitor (CGM), insulin pump, insulin pen, blood glucose (blood sugar) monitor, or other diabetes technology, they've become an essential part of diabetes management.