Pathophysiology of diabetes mellitus

Diabetes mellitus

1. Pathophysiology of diabetes mellitus

2. Diabetes mellitus It is a group of metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion, defects in insulin action (“insulin resistance”) , or both. If left untreated, diabetes can cause many complications. - long term damage, dysfunction, and failure of various organs, especially the Eyes Kidneys Nerves Heart Blood vessels

3. Insulin Insulin is the principal hormone that regulates the uptake of glucose from the blood into cells of the body, - especially liver, adipose tissue and muscle, except smooth muscle, in which insulin acts via the IGF-1 (Insulin-like growth factor -1). Therefore, deficiency of insulin or the insensitivity of its receptors plays a central role in all forms of diabetes mellitus. Insulin plays a critical role in balancing glucose levels in the body: It can inhibit the breakdown of glycogen or the process of gluconeogenesis. It can stimulate the transport of glucose into fat and muscle cells. It can stimulate the storage of glucose in the form of glycogen.

4. INSULIN Insulin is released into the blood by beta cells( β cells), found in the islets of Langerhans in the pancreas, in response to rising levels of blood glucose, typically after eating. Lower glucose levels result in decreased insulin release from the beta cells and results in the breakdown of glycogen to glucose. This process is mainly controlled by the hormone glucagon , which acts in the opposite manner to insulin. The body obtains glucose from three main places: The intestinal absorption of food The breakdown of glycogen , the storage form of glucose found in the liver. Gluconeogenesis the generation of glucose from non-carbohydrate substrates in the body.

5. Classification of diabetes There are three main types of diabetes mellitus: Type 1 DM Type 2 DM Gestational Diabetes

6. Type 1 Diabetes mellitus due to pancreatic islet β cell destruction predominantly by an autoimmune process. Results from the pancreas’s failure to produce enough insulin. It is usually diagnosed in children and young adults. This form was previously referred to as “ insulin-dependent diabetes mellitus’’ ( IDDM) or “juvenile diabetes’’ Only 5% of people with diabetes have this form of the disease

7. P a tho g enes i s Susceptibility genes identified e.g. HLA haplotypes DR3 & DR4. genetic predisposition environmental factors viral infections stress toxins Type 1 Diabetes cell-mediated autoimmune destruction of the beta-cells of the pancreas by auto- antibodies absolute insulin deficiency

8. Sequence of events in the development of Type 1 Diabetes

9. TYPE 2 Diabetes mellitus It is the more prevalent form and results from insulin resistance ,a condition in which cells fail to respond to insulin properly with a defect in compensatory insulin secretion. This form was previously referred to as " non insulin- dependent diabetes mellitus" (NIDDM) or "adult-onset diabetes“. The primary cause is excessive body weight and not enough exercise.

10. P a tho g enes i s genetic predisposition environmental factors insulin resistance and inadequate compensatory insulin secretory response relative insulin deficiency Type 2 Diabetes Diet Physical inactivity  Obesity

11. Gestational diabetes mellitus (GDM) It is the third main form and occurs in pregnant women without a previous history of diabetes. GDM resembles type 2 DM in several aspects. Involves a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2–10% of all pregnancies and may improve or disappear after delivery.

12. GDM Gestational diabetes can damage the health of the fetus Risks to the baby include: Macrosomia (high birth weight) Congenital Heart Defects Central Nervous System Abnormalities Skeletal Muscle Malformations.

13. Clinical presentation of DM Asymptomatic (particularly type 2 DM) Features resulting from the effects of insulin deficiency/resistance The 3 Polys : Polyuria Polydipsia Polyphagia Complications: Acute: coma (ketoacidosis) (particularly type 1 DM) Chronic: macrovascular and microvascular

14. Clinical Features of DM due to insulin lack

15. Complications Hyperglycaemia Excess entry of glucose into non-insulin dependent tissues Nerves Lens Kidneys Blood vessels Increased intracellular glucose -> metabolized to sorbitol -> fructose -> increased osmotic load -> influx of water -> osmotic cell injury E.g. lens -> cataract

16. Microvascular complications Retinopathy Nephropathy Neuropathy Impaired skin healing -> foot ulcers

17. Diabetic Retinopathy Capillary microaneurysms Macular oedema neovascularization ->partial or total vision loss

18. Diabetic nephropathy Thickening of glomerular basement membrane Mesangial cell expansion Glomerulosclerosis Glomerular hypertension Progressive decline in glomerular filtration rate N ephrotic syndrome (leakage of albumin)/ renal failure

19. Diabetic neuropathy due to direct effects of hyperglycaemia and intracellular metabolic changes Impaired nerve function (sensory, motor) Symmetric polyneuropathy (distal feet and hands) Autonomic neuropathy Cranial neuropathy Mononeuropathy (median nerve, peroneal nerve) “ diabetic foot ”

20. Macrovascular complications Large vessel atherosclerosis (due to hyperinsulinemia, dyslipidaemia,hyperglycaemia ) Coronary arteries -> myocardial ischaemia /infarction Cerebral arteries-> transient ischaemic attacks; cerebrovascular events -> stroke Peripheral artery disease -> ischaemia-> intermittent claudication

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