- Type 2 diabetes is characterized by insulin resistance, inadequate insulin secretion from the pancreas, and elevated blood glucose levels. This can lead to complications affecting small blood vessels (microvascular), large blood vessels (macrovascular), and nerves (neuropathic). - Insulin resistance develops when the body does not properly use insulin and is associated with obesity. Over time, this can cause the pancreas to lose its ability to produce enough insulin to compensate, leading to high blood glucose and insulin levels. - Chronic high blood glucose can damage tissues and cells in the body through processes like glucotoxicity and lipotoxicity, worsening insulin resistance and beta cell function over time in a vicious cycle. This puts individuals at higher risk for

2. Diabetes mellitus is a chronic disease characterized by derangement in carbohydrates, fat and protein metabolism

3. Type 2 diabetes mellitus comprises an array of dysfunctions resulting from: the combination of resistance to insulin action inadequate insulin secretion. It is disorders are characterized by hyperglycemia and associated with microvascular (ie, retinal, renal, possibly neuropathic), macrovascular (ie, coronary, peripheral vascular), and neuropathic (ie, autonomic, peripheral) complications.

4. Type 2 diabetes Insulin resistance  -cell dysfunction

5. Obesity Insulin resistance Abnormal insulin secretion Excess glucose production Beta-cell failure

7. Insulin resistance is a condition in which the body produces insulin but does not use it properly.

8. The circulating free fatty acids associated with obesity also responsible for insulin resistance of the muscle and liver.

9. Decreased glucose uptake by skeletal muscle and adipose tissue. Increased glucose output by Liver-Gluconeogenesis. In the early stages of obesity the pancreas compensates for the IR by overproducing insulin so that glucose homeostasis is maintained. This leads to HYPERGLYCEMIA & HYPER INSULINEMIA

10. Chronic hyperglycemia Glucotoxicity 2 Lipotoxicity 3 Oversecretion of insulin to compensate for insulin resistance 1,2  -cell dysfunction

11. The elevated levels of free fatty acids and or cytokines lead to gradual loss of the ability of the pancreas to overproduce insulin , a process called decompensation- Lipotoxity Glucose, the main regulator of insulin secretion and production, exerts negative effects on beta-cell function when present in excessive amounts over a prolonged period- glucotoxicity .

12. IR Insulin resistance Liver Muscle Adipose tissue  Glucose output  Glucose uptake  Glucose uptake Hyperglycemia

13. It rarely develops in DM-II Insulin present in DM-II is enough to prevent uncontrollable release of fatty acids from adipocytes and fattyacids reaching the liver or synthesized de novo are directed to triacyglycerol.

14. If it is develops: Insulin Deficiency Increased Glycogenolysis Increased Gluconeogenesis Increased Hepatic glucose output Decreased Peripheral glucose uptake Elevates blood glucose Increased Lipolysis Increased Release of FFA in liver Increased VLDL & ketones Ketonemia and hyperTG Acidosis & Diuresis

15. It is a characteristics of DM-II Results from an increase in VLDL without hyperchylomicronemia. This happens by hepatic synthesis of fatty acids and diversion of free fatty acids reaching the liver in to triacylglycerol and VLDL.

16. Normal Normal TG Type 2 diabetes High TG Low HDL cholesterol Small dense LDL (diabetic dyslipidaemia) Normal insulin level Impaired insulin action to inhibit VLDL production Increased liver fat Insulin deficiency exacerbates hypertriglyceridaemia

17. Chronic complications –  Microvascular- retinopathy , nephropathy, neuropathy.  Macrovascular - cardiovascular, cerebrovascular, peripheral vascular diseases.  Acute complications – diabetic ketoacidosis, hyperosmalor coma.

18. Hyperglycaemia in insulin independent tissues (nerve, lens, retina) gives rise to polyol formation. The enzyme aldose reductase catalyses the reduction of glucose to sorbitol, which is converted to fructose. Sorbitol does not easily easily cross cell membranes and its accumulation may cause damage by osmotic effect (e.g. in the lens). Sorbitol trapped in retinal cells, the cells of the lens, and the Schwann cells that myelinate peripheral nerves can damage these cells, leading to retinopathy, cataracts and peripheral neuropathy.

20. Carbohydrate Glucose(G)-I (I)-Insulin Carbohydrate Acarbose Reduces absorption Sulphonylurea Repaglinide Stimulates pancreas Metformin Reduces hepatic glucose output (??muscle/fat effects) Thiazolidinediones Reduce Insulin Resistance