Most of the patients with type II diabetes are overweight. The obesity is the result of a genetic disposition, too large an intake of food, and too little physical activity. The imbalance between energy supply and expenditure increases the concentration of fatty acids in the blood. This in turn reduces glucose utilization in muscle and fatty tissues. The result is a resistance to insulin, forcing an increase of in sulin release. The resulting down-regulation of the receptors further raises insulin resistance. Obesity is an important trigger, but not the sole cause of type II diabetes. More important is the already existing genetic disposition to reduced insulin sensitivity. Frequently, insulin release has always been abnormal. Several genes have already been defined that promote the development to obesity and type II diabetes. Among other factors, the genetic defect of a mitochondrial decoupling protein limits substrate consumption. If there is a strong genetic disposition, type II diabetes can already occur at a young age (maturity-onset diabetes of the young [MODY]).
Reduced insulin sensitivity predominantly affects the insulin effect on glucose metabolism, while the effects on fat and protein metabolism are still well maintained.