Molecular links between Obesity and Diabetes: “Diabesity”

Severe obesity represents a major risk factor for the development of type 2 diabetes mellitus (T2DM). Due to the strong association of obesity and diabetes, the term “diabesity” was coined, suggesting a causal pathophysiological link between both phenomena. The majority of individuals with T2DM are obese, highlighting the pivotal role of increased adiposity as a risk factor for diabetes. However, only a relatively small fraction of obese individuals will develop T2DM. On a population level, the link between obesity and its secondary complications is well described. However, the molecular mechanisms underlying these complications are still poorly understood. Three main hypotheses have been developed in recent years to bridge the gap between epidemiology and pathobiochemistry: (1) The “inflammation hypothesis” asserts that obesity represents a state of chronic inflammation where inflammatory molecules produced by infiltrating macrophages in adipose tissue exert pathological changes in insulin-sensitive tissues and β-cells. (2) The “lipid overflow hypothesis” predicts that obesity may result in increased ectopic lipid stores due to the limited capacity of adipose tissue to properly store fat in obese subjects. Potentially harmful lipid components and metabolites may exert cytotoxic effects on peripheral cells. (3) The “adipokine hypothesis” refers to the principal feature of white adipose cells to function as an endocrine organ, and to secrete a variety of hormones with auto- and paracrine function. Expanding fat stores can cause dysfunctional secretion of such endocrine factors, thereby resulting in metabolic impairment of insulin target tissues and eventually failure of insulin producing β-cells. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.