From obesity to diabetes: why, when and who?

Obesity is considered as the most important risk factor for type 2 diabetes. We will briefly discuss why does obesity predispose to diabetes, when does diabetes occur in obese subjects and who among obese individuals is particularly prone to develop diabetes. Obesity, especially intraabdominal adiposity, is associated with increased FFA plasma concentrations which exert a major negative effect on insulin sensitivity at both muscular and hepatic sites. Various metabolic, haemodynamic and hormonal theories have been proposed to explain insulin resistance in obese subjects. A specific role of TNF-alpha has been recently suggested. However, besides insulin resistance, defective insulin secretion is a prerequisie for the development of overt type 2 diabetes. Both lipotoxicity and glucotoxicity may initiate and perpetuate a vicious circle responsible for the metabolic deterioration. Diabetes occurs as a late phenomenon in obesity and is preceded by years of impaired glucose tolerance. The progression to diabetes is heralded by an inability of the B cell to maintain its previously high rate of insulin secretion in response to glucose in face of insulin resistance. This propensity to develop type 2 diabetes may be genetically determined and/or triggered by environmental factors. The evolution from obesity to diabetes represents a continuum that progresses through different phases in which defects in both insulin action and insulin secretion play a critical interaction and must be looked at in concert.