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A type of diabetes that is first recognized during pregnancy or develops during pregnancy.

Usually disappears after pregnancy but increases the risk of T2DM development

Risk Factors: previous history of gestational diabetes, increased weight, overweight

Treatment: diet, exercise. Blood glucose levels with metformin or insulin treatment.

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Human Insulin Structure

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Diagram: normal glucose & insulin profiles 

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Diagram: normal glucose & insulin profiles 

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Table: target goals for diabetic patient 

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Table: target goals for diabetic patient 

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Urine Tests

Hime blood glucose testing

Glycosylated haemoglobin and fructosamine

Glucose targets for diabetes management

Regular checks

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Hypoglycaemia. occurs before meal, after exercise, at night.

This can cause sweating, tremor, heart palpitations and even coma sometimes

Mention nocturnal hypoglycaemia etc etc

Mild hyperglycaemia
Severe hyperglycaemia

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Injection
Insulin administration

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Tablet Treatment for T2DM

Biguanide (metformin)

Best validated primary treatment for type 2 diabetes. Activates AMP-kinase which is involved in energy metabolism, but its precise mechanism is unknown.
Its effect is to reduce the rate of gluconeogenesis, and hence hepatic glucose output, and to increase insulin sensitivity.
It does not affect insulin secretion, does not induce hypoglycaemia and does not predispose to weight gain.
Side effects: anorexia, epigastric discomfort and diarrhoea. Risk of lactoacidosis is present.
Metformin is contraindicated to patients with severe hepatic and renal disease

Sulphonylureas

Complication: can induce sever hypoglycaemia

Meglitinides

Contraindication: not readily used because it's expensive

Thiazolidinediones

Mechanism of action not fully understood. But they reduce hepatic glucose production, and also enhance peripheral glucose uptake

Complication:

Dipeptidyl peptidase-4 inhibitors

Enhance the incretin effect. Increase insulin secretion and reduce glucagon secretion through inhibition of dipeptidyl peptidase 4 (DPP4) enzyme. It inactivates GLP-1 hence increases its susceptibility.
Name of the drug:
Complication: pancreatitis....

Sodium/glucose transporter 2 inhibitors

Inhibit glucose transport.

Complications: genital infection, increase in UTI

^^ fill all these later

Injection Therapies

GLP-1 Agonists
They promote insulin release, inhibit glucagon release, reduce appetite and delay gastric emptying, thus blunting the post- prandial rise in plasma glucose and promoting weight loss. At present they are used as an alternative to insulin, particularly in the overweight. Studies show that it promotes b-cell replication in rodent models.

Disadvantage: need for subcutaneous injection

Side effects: nausea, acute kidney injury, pancreatitis.

Other Therapies

Intestinal enzyme inhibitors

Orlistat

Colesevelam

Gastric banding & gastric bypass surgery

Insulin Treatment

Short-acting insulins

Now mostly made from biosynthetic human insulin. Pre-meal injection. Absorbed slowly but peaks after around 16 minutes. Rapids action.

Intermediate and longer acting insulins

Longer acting insulin. The action of insulin is prolonged with....

Practical Management of diabetes
Needles

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Patient education and community care

Diet

Carbohydrates

Prescribing a diet

Normal healthy diet but diet low in carbs is recommended. Add info here

Exercise

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Macrovascular complications

Include retinopathy, nephropathy, and neuropathy, risk of stroke

Microvascular complications

Affects retina, glomeruli, includes ischemic heart disease, peripheral vascular disease, and cerebrovascular disease

Diabetic eye disease (retinopathy)

Diabetic kidney disease (nephorpathy)

Glomeruli damage ischemic or infection due to chronic hyperglycaemia. Increased glomeruli filtration that can cause damage due to increased pressure. Can lead to glomerular sclerosis

Diabetic neuropathy

Diabetes can damage peripheral nervous tissue.

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Diabetic ketoacidosis

Uncontrolled catabolism. Lipids are being broken down for energy. You get hyperventilation, nausea, specific breath smell

Hyperosmolar hyperglycaemic state

Sever hyperglycaemia that develops without ketosis. Characteristic for T2DM. Present in undiagnosed patients.

Lactic acidosis

Elevated lactic acid levels which induce metabolic acidosis. Less common but the mortality is quite high

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WHO Criteria

Pre-diabetes

Impaired glucose tolerance

Impaired fasting glucose

This diagnostic category: fasting plasma glucose between 6.1 and 6.9 mmol/L. It is not a clinical entity, but indicates future risk of frank diabetes and cardio- vascular disease.

Haemoglobin A1c

HbA1c is an integrated measure of an individual’s prevailing blood glucose concentration over several weeks (see below). Additional test you can do looking how much sugar is attached to haemoglobin where HbA1c >6.5% (48 mmol/mol) would be considered diagnostic of diabetes, whereas a level of 5.7–6.4% (39–46 mmol/mol) would denote increased risk of diabetes.

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Tests are often not necessary because symptoms are quite clear.

Evidence of weight loss and dehydration may be present, and the breath may smell of ketones. Older patients may present with established complications, and the presence of the characteristic retinopathy is diagnostic of diabetes.

Patients with severe insulin resistance may have acanthosis nigricans, which is characterized by blackish pigmentation at the nape of the neck and in the axillae.

For testing options and criteria:
Refer to the table below

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Acute

Polyuria, polydipsia, weight loss, breakdown of fat and muscle, ketonuria and ketoacidosis

Subacute

The clinical onset may be over several months or years, particularly in older patients. Thirst, polyuria and weight loss are typically present but patients may complain of such symptoms as lack of energy, visual blurring (owing to glucose-induced changes in refraction) or pruritus vulvae or balanitis that is due to Candida infection.

Complications

Retinopathy, polyneuropathy (numbness), ererctile dysfunction, skin infections.

Asymptomatic Diabetes

Can also be asymptomatic (detected through routine examination). Glycosuria or a raised blood glucose may be detected on routine examination. Glycosuria is not diagnostic of diabetes but indicates the need for further investigations.

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1) Genetic Susceptibility
2) Environmental Factors
3) Inflammation
CRP levels are elevated. Increased fibrinogen and plasminogen activator inhibitor-1 (PAI-1) (contributes to cardiovascular risk). Circulating levels of the pro-inflammatory cytokines TNF-α and IL-6 are elevated in both diabetes and obesity.

4) Insulin Defects

secretion

action

^^ some these up later

5) Prevention

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Covered in al population but its increasing due to Western lifestyle.

Associated with central obesity, hypertension, hypertriglyceridaemia, a decreased HDL-cholesterol, disturbed haemostatic variables and modest increases in a number of pro-inflammatory markers.

Metabolic syndromes

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1) Genetic Susceptibility
HLA system. Located on chromosome 6. More than 90% of patients with type 1 diabetes carry HLA- DR3-DQ2, HLA-DR4-DQ8 or both, as compared with some 35% of the background population. A major factor in genetic susceptibility.

2) Autoimmunity
Type 1 diabetes is associated with other organ-specific autoimmune diseases including autoimmune thyroid disease, coeliac disease, Addison’s disease and pernicious anaemia.
3) Environmental Factors
Clean environment hypothesis = linked to the development of autoimmunity.
4) Pre-type 1 DM and prevention
Children who test positive for two or more autoantibodies have a >80% risk of progression to diabetes, and the risk approaches 100% in those who additionally lose their first phase insulin response to intravenous glucose and/or develop glucose intolerance. This means that T1DM can be prevented  with this form of prediction

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Type 1 diabetes is a disease of insulin deficiency.

In western countries almost all patients have the immune-mediated form of the disease, otherwise known as type 1A. Type 1 diabetes is a disease of childhood, reaching a peak incidence around the time of puberty, but can present at any age.

Northern European countries have the highest rates of T1DM, but incidence is increasing globally.

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Diabetes mellitus (DM) is a syndrome of chronic hyperglycaemia due to relative insulin deficiency, resistance or both.

Type 1 diabetes mellitus
has an immune pathogenesis and is characterized by severe insulin deficiency. Early onset.

Type 2 diabetes mellitus
Results from a combination of insulin resistance and less severe insulin deficiency. Late onset. More responsive to environmental factors because it depends on the lifestyle, however genes also do play a role.

What is the difference?
Type 1 and type 2 diabetes represent two distinct diseases from the epidemiological point of view, but clinical distinction can sometimes be difficult. The two diseases should from a clinical point of view be seen as a spectrum, distinct at the two ends but overlapping to some extent in the middle.

Hybrid forms exist. More of these are recognized now.

Refer to the table below for specific distinctions

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1) Production
About 200g of glucose is produced and utilized daily. More than 90% is derived from liver glycogen and hepatic gluconeogenesis, and the remainder from renal gluconeogenesis.

2) Utilisation
The main consumer of glucose is brain. Glucose uptake by the brain is obligatory and is not dependent on insulin, and the glucose
used is oxidized to carbon dioxide and water. (Newer studies show that it is in a way dependent on insulin).

Other tissues,
such as muscle and fat, are facultative glucose consumers. Insulin facilitates glucose uptake into these tissues by binding to GLUT-4 receptor of the cells found in these tissues. It lowers or raises the uptake threshold. Glucose is either stored of metabolized in these tissues.

3) Hormonal Regulation
4) Glucose Transport
5) Insulin Receptor
This is a glycoprotein (400 kDa), situated on the cell membrane of many cells. It consists of a dimer with two α-subunits, which include the binding sites for insulin, and two β-subunits, which traverse the cell membrane. When insulin binds to the α-subunits it induces a conformational change in the β-subunits, resulting in activation of tyrosine kinase and initiation of intracellular events cascade. One consequence of this is migration of the GLUT-4 glucose transporter to the cell surface and increased transport of glucose into the cell. The insulin-receptor complex is then internalized by the cell, insulin is degraded, and the receptor is recycled to the cell surface.