Pathophysiology
- Type 2 is more complex than T1DM, with multiple mechanisms at work
- Insulin resistance – Impaired sensitivity to insulin in the muscle, fat, and liver
- This is the main factor in T2DM
- The cause of this is unclear but is associated with adiposity, inactivity, and NAFLD
- Progressive B cell failure also causes reduced insulin release
- Therefore they can still benefit from insulin therapy
- This progresses with time
- Not autoimmune (unlike type 1)
- 20% of patients ultimately progress to no insulin release at all
- a-cells remain normal and this further contributes to hyperglycaemia via glucagon release which is actually increased(to provide more glucose to the body’s cells by increasing the extracellular glucose)
- Insulin resistance – Impaired sensitivity to insulin in the muscle, fat, and liver
Metabolic changes in T2DM
- Like T1DM, metabolic disturbances again occur due to abnormal insulin
In most patients with T2DM, only the pro-anabolic effect of insulin is lost
- This is because insulin resistance is the main factor
- Even a small amount of insulin – as in T2DM – can prevent gluconeogenesis
- Only patients who lose all ability to make insulin lose this (about 20% of patients with late-stage T2DM)
- Hyperglycaemia is the main issue – the features are identical to T1DM
- Increased infection risk
- Glycosuria => osmotic diuresis symptoms
Natural history of T2DM
- With progression, several changes develop:
- Insulin secretion becomes impaired (eventually completely ceasing)
- Resistance plateaus quickly
- Glucose becomes progressively more poorly controlled because of the above reasons