Insulin resistance versus impaired insulin secretion as the genetic basis for type 2 diabetes

Abstract

The relative roles of impaired insulin secretion and insulin resistance in the pathogenesis of type 2 diabetes continue to be controversial. The controversy centers on two issues: the most important genetic factor in type 2 diabetes and the most important factor determining the magnitude of hyperglycemia. This review attempts to determine the most important genetic factor. It is widely believed that insulin resistance is the primary genetic factor in type 2 diabetes. The original bases for this belief have come under question, however, and recent studies using sophisticated methods (eg, glucose clamps, minimal modeling) to assess insulin secretion and insulin sensitivity in certain well-characterized individuals have tended to support the view that impaired insulin secretion is the primary genetic factor in type 2 diabetes.