29th May 2025

Pathophysiology

In T2DM, the desensitisation of the peripheral tissues to the action of insulin leads to chronic hyperglycaemia, which inhibits pancreatic beta-cell proliferation and secretion of insulin. Therefore, the amount of glucose entering cells and being metabolised is reduced, triggering the compensatory release of glucagon, cortisol, growth hormone and catecholamines to stimulate glycogenolysis and gluconeogenesis, forming a vicious cycle. Greater circulating glucose significantly increases the serum osmolality (Osmolality = 2(Na) + glucose/18 + BUN/2.8) and osmotic gradient, pulling water into the vessels from the extravascular space. Water and electrolytes are lost in the urine leading to dehydration.

The main differentiating feature from DKA is that there is very little production of ketone bodies as there is still some production of insulin, which inhibits ketogenesis. Patients therefore don’t become severely acidotic.