The precise aetiology of diabetes mellitus remains unknown. There is clearly both a genetic element which is almost certainly multifactorial, due to the multiple and additive effects of genes especially in younger patients, together with environmental factors, especially in older patients. Evidence is increasing that the genetic element is associated with an underlying defect of the beta cells with a characteristic delayed and subnormal insulin secretion in response to glucose or other insulinogenic stimuli. The same hyposecretory response can often be found in many close relatives and in ‘prediabetes’ where standard carbohydrate tolerance is still normal. The nature of the defect of the beta cell, its link with the genetic mechanism, and the mechanism leading to total islet failure in some diabetics is not known. Many factors may be involved simultaneously in a single individual and apart from multiple genes, certain non-genetic factors such as obesity, pregnancy, infection and other stress which result in increased insulin antagonism, lead to additive strains on islet cell function, and may determine the onset of the overt disease in hereditarily predisposed individuals.
The Pathogenesis of Diabetes Mellitus
