Diabetes mellitus type 2

Diabetes mellitus type 2

Definition

Type 2 diabetes mellitus is a chronic disorder of carbohydrate, fat and protein metabolism with hyperglycaemia as its principal feature. It is characterised by impaired insulin secretion and insulin resistance.

Type 2 diabetes used to be called non-insulin dependent diabetes (NIDDM) but this term is confusing, as many patients require insulin for good diabetic control.

Incidence/prevalence

Approximately 2% prevalence in UK; 75% of UK diabetic patients.

Age

Increases with age.

Sex

M = F

Geography

Wide geographic variation. More common in Asian immigrants to UK than indigenous population.

Aetiology

A combination of genetic and environmental factors both in the development of insulin resistance and impaired insulin secretion. The overall concordance in monozygotic twins is up to 90%. Environmental factors include diet both in relation to obesity, lack of exercise and the epidemiological evidence that once ‘westernised’ ethnic migrants have significantly increased prevalence.

Maturity onset diabetes of the young (MODY) occurs in a small subgroup of patients who present under the age of 25. MODY results from specific monogenetic disorders which are inherited in an autosomal dominant fashion.

Pathophysiology

Insulin resistance in the liver, skeletal muscle and adipose tissue (by about 40%) secondary to a decrease in the number of insulin receptors, decreased receptor tyrosine kinase activity and post-receptor defects causing impaired glucose transport.

Defective insulin secretion due to islet cell dysfunction with increased secretion of proinsulin and cleavage products. Amylin, an amyloid protein, is found in increased amounts in the islets cells. It may disrupt the normal insulin secretion.

Reduced effective insulin causes increased gluconeo-genesis by the liver and reduced peripheral uptake, leading to hyperglycaemia. However, there is sufficient insulin to suppress lipolysis and ketogenesis, so that ketosis and ketoacidosis do not occur.

Clinical features

Type 2 diabetes may be diagnosed on routine blood testing (this may follow detection of glycosuria). Symptomatic patients have an insidious onset of polyuria, polydipsia and are usually obese. Diabetes causes an increased predisposition to infections, such as abscesses, pyelonephritis and candidiasis.

Complications

·        Acute complications: Hyperglycaemic coma which is usually hyperosmolar non-ketotic coma and complications of therapy such as hypoglycaemia due to insulin or sulphonylureas, metformin-induced lactic acidosis.

·        Chronic complications include:

Microvascular (microangiopathic) disease: Includes diabetic maculopathy and retinopathy, nephropathy and neuropathy.

Macrovascular (large vessel) disease: Atherosclerosis which leads to complications such as myocardial infarction, strokes, gangrene of the legs and mesenteric artery occlusion.

Investigations

The diagnostic criteria are as for type 1 diabetes.

Management

Involves changing the diet, lifestyle (exercise, losing weight) and using oral hypoglycaemic drugs if the for-mer are not effective. Some patients require insulin for adequate glycaemic control.

Loss of weight by an obese patient can lead to normalisation of blood glucose levels and resolution of symptoms. It also reduces insulin resistance. Dietary recommendations include:

·        Increase complex carbohydrates (CHO) i.e. bread, cereal, pasta.

·        Decrease refined sugars i.e. cakes and sweets. Decrease fats, particularly saturated fat.

·        Decrease alcohol if excessive, and dry wine is better than beer (less CHO).

Oral hypoglycaemic drugs:

Biguanides (metformin) reduce insulin resistance, but may cause lactic acidosis with a mortality rate of up to 50%. It may be prevented by avoiding the use of biguanides in patients with moderate renal or hepatic failure.

Sulphonylureas (glicazide and glibenclamide) increase insulin secretion by the Î²-cells.These increase levels of plasma insulin and may result in more weight gain, insulin resistance and a higher risk of complications, they are often avoided in the early treatment, unless symptoms are severe.

Thiazolidinediones (glitazones) increase peripheral insulin sensitivity. They take 3–4 months to achieve maximal effect. They can be used as monotherapy or combined with other drugs.

α−glucosidase inhibitors (acarbose) which reduce the activity of the enzyme responsible for digesting carbohydrates in the intestine, thus delaying and reducing postprandial blood glucose peaks.

Management also requires careful monitoring for and treatment of complications.

Prognosis

75% of patients die from vascular and related disease.