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 :
- Reduced anabolism (results in hyperglycaemia)
- Increased catabolism (gluconeogenesis)
Both of these are propagated by stress hormones (e.g. cortisol) and glucagon
- 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
- 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