Pathophysiology: T1DM

Pathophysiology of T1DM
  • There is no insulin release due to autoimmune B cell destruction  in the pancreas by Anti-Islet and Anti-GAD antibodies
  • Therefore tissues remain sensitive to exogenous insulin (which is important for treatment
Metabolic changes in T1DM
  • The complete lack of insulin action causes 2 main metabolic issues :
    1. Reduced anabolism (results in hyperglycaemia)
    2. Increased catabolism (gluconeogenesis)

Both of these are propagated by stress hormones (e.g. cortisol) and glucagon

  1. Hyperglycaemia occurs because  glucose remains in blood
    • A. Infection risk increases
    • B. Glycosuria – glucose is excreted in the urine because it cannot be reabsorbed.
      • => Osmotic diuresis – Glucose in the urine pulls water/salt out with it
      • =>  Salt and water depletion viapolyuria/nocturia which causes
        • => Polydipsia
        • => Hypotension and tachycardia
        • => Can ultimately cause death
  1. Gluconeogenesis via unrestrained lipolysis/proteolysis  in the absence of insulin’s anti-catabolic effects leads to:
    • Lipolysis=> Weight loss
    • Proteolysis=> Muscle wasting
    • Ketogenesis is the main type of gluconeogenesis to occur
      • DKA occurs where more ketones are made than can be used (See DKA)
  • Note that gluconeogenesis is not an issue in Type 2 because even a small amount of insulin can suppress catabolism