Diabetes Mellitus

• The pathogenesis of Type 1 Diabetes Mellitus involves the destruction of islets caused by immune effector cells directed against endogenous β-cell antigens.
• The metabolic defects in Type 2 DM include decreased ability of peripheral tissues to respond to insulin and beta cell dysfunction, manifested as inadequate insulin secretion in the face of insulin resistance and hyperglycemia.
• The main difference in insulin levels between Type 1 and Type 2 diabetes mellitus is that in Type 1 diabetes, there is a progressive decrease in insulin levels, while in Type 2 diabetes, there is an early increase in blood insulin followed by a normal or moderate decrease in insulin levels.
• The main difference in weight between Type 1 and Type 2 diabetes mellitus is that Type 1 diabetes is associated with normal weight or weight loss, while Type 2 diabetes is associated with obesity in 80% of cases
• Diabetes Mellitus is group of metabolic disorders characterized by hyperglycemia
• • Diagnosis:
  • A random blood glucose concentration of ≥ 200mg/dL with classical signs and symptoms
  • A fasting glucose concentration of ≥ 126mg/dL on more than one occasion
  • An abnormal oral glucose tolerance test with a glucose concentration of ≥ 200mg/dL two hours after a standard carbohydrate load
• • Type 1 DM (most common in patients under 20) is an autoimmune disease characterized by pancreatic β-cell destruction and absolute insulin deficiency.
  • Type 2 DM (most patients = overweight) is characterized by peripheral resistance to insulin action and inadequate insulin secretion by the pancreatic β-cells .
• • The pathogenesis of Type 1 Diabetes Mellitus involves the destruction of islets by immune effector cells.
  • This destruction is caused by a failure of self-tolerance in T cells, which can be attributed to:
  • Defective clonal deletion of self-reactive T cells in the thymus
  • Defects in the functions of regulatory T cells
  • Resistance of effector T cells to suppression by regulatory cells
• • Auto - antibodies against a variety of beta cell antigens can be detected in the blood of individuals with Type 1 DM.
  • Vulnerable location = Chromosomal region that codes for class II MHC molecules on 6p21 (HLA - D)
• Microscopic findings : include necrosis of beta cells and lymphocytic infiltration(insulitis) in the early stages of the disease
• • Metabolic defects in Type 2 DM include:
  • Decreased ability of peripheral tissues to respond to insulin
  • Beta cell dysfunction, leading to inadequate insulin secretion in the face of insulin resistance and hyperglycemia
• • Insulin resistance is a failure of target tissues to respond normally to insulin.
  • This leads to a:
  • Failure of glucose uptake and glycogen synthesis in muscle
  • Reduced glycolysis and fatty acid oxidation in the liver
  • Inability to suppress hepatic gluconeogenesis
• • Mechanisms of beta cell dysfunction and insulin resistance in Type 2 DM include the effects of free fatty acids (FFAs).
  • FFAs can:
  • Cause Beta cell dysfunction
  • Induce insulin resistance in target tissues
  • Stimulate the secretion of pro-inflammatory cytokines
• • Mechanisms of beta cell dysfunction and insulin resistance in Type 2 DM include the effects of free fatty acids (FFAs).
  • FFAs can:
  • Cause Beta cell dysfunction
  • Induce insulin resistance in target tissues
  • Stimulate the secretion of pro-inflammatory cytokines