Diabetes Mellitus Type 2

Diabetes Mellitus Diabetes mellitus is “a group of common metabolic disorders that share the phenotype of hyperglycemia.” (HPIM 17th ed.) “Diabetes is a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces.” (WHO, 2011)

Diabetes Mellitus Type 2 DM is characterized by insulin resistance and abnormal insulin secretion According to the WHO, there were 2,770,000 Filipinos with Type 2 DM in 2000 and projects that by 2030, this number will rise to 7,798,000 and the Philippines is going to be in the Top 10 countries with the highest number of people with diabetes.

DM Type 2 Pathophysiology Early stages: near normal glucose tolerance despite insulin resistance Pancreatic β-cells compromise and ↑ insulin output ↑ insulin resistance ↑ compensatory hyperinsulinemia Pancreatic β-cells unable to sustain hyperinsulinemic state Impaired glucose tolerance

DM Type 2 Pathophysiology Impaired glucose tolerance ↓ insulin production ↑ hepatic gluconeogenesis Overt diabetes with fasting hyperglycemia Pancreatic β-cell failure ↑ postprandial glucose

DM Type 2 Pathophysiology Metabolic Abnormalities Abnormal muscle & fat metabolism Impaired insulin secretion Increased hepatic glucose and lipid production

DM Type 2 Pathophysiology Abnormal muscle and fat metabolism Obesity Genetic susceptibility Insulin resistance Impaired glucose utilization hyperglycemia ↑ hepatic gluconeogenesis ↑ FPG ↓ peripheral glucose usage Postprandial hyperglycemia ↑ impairement in glycogen formation of skeletal muscles

DM Type 2 Pathophysiology Impaired insulin secretion 2nd genetic defect Insulin resistance ↑ insulin secretion Mild insulin secretory defect Grossly inadequate insulin secretion Pancreatic β-cell failure

DM Type 2 Pathophysiology Increased hepatic glucose and lipid production Liver insulin resistance Unsuppressed liver gluconeogenesis Fasting hyperglycemia ↓ glycogen storage

DM Type 2 Pathophysiology Increased hepatic glucose and lipid production Adipose tissue insulin resistance + obesity ↑ FFA acid flux from adipocytes ↑ hepatic lipid (VLDL, Triglyceride) synteheis Steatosis in liver Non-alcoholic fatty liver disease Abnormal liver Fxn Tests

DM Type 2 Pathophysiology Increased hepatic glucose and lipid production Adipose tissue insulin resistance ↑ FFA flux from adipoctyes ↑ lipid synthesis (VLDL, triglyceride) in hepatocytes Steatosis in liver Nonalcoholic fatty liver diseae Abnormal liver function tests Dyslipidemia (↑ trig, ↓ HDL, ↑ LDL)

DM and Psoriasis IL-23 Stimulate Th 17 cells Release IL-17 Induce psoriatic cytokines TNF-α, IL-1, IL-6, IL-8 Insulin resistance Dyslipidemia Endothelial production

DM and Cancer Hyperinsulinemia ↓ IGFBP I, II, III ↓ IGF action ↑ free/bioactive IGF-I levels ↓ cellular apoptosis ↑ tumor growth ↑ survival and progression of early malignant cells