28th May 2025

Aetiology

The initial pathogenesis of T2DM is characterised by the desensitisation of the liver and skeletal muscle to the action of insulin, aggravated mainly by obesity, increasing age and genetic predisposition. The body’s normal homeostatic response involves increasing the secretion of insulin from beta-cells at the islets of Langerhans in the Pancreas. However, when this relationship decompensates, the beta-cells are unable to secrete sufficient insulin to bring blood glucose under control. Hyperglycaemia has an inhibitory effect on both beta-cell insulin secretion and cell turnover, leading to a reduction in cell function and mass. Therefore, as the disease progresses there is less capacity for insulin production as well as increasing desensitisation of peripheral tissues. Several other processes have been identified that contribute to the development of T2DM, including increased lipolysis, hyperglucagonemia, increased renal glucose reabsorption and resistance to the action of incretin.