The Effect of Diabetes-associated Gene Variation on Glucose Metabolism in Humans

Type 2 diabetes is a common metabolic disorder arising from a complex interaction between genetic predisposition and the environment. The development of this disorder is preceded by impaired glucose tolerance and elevated fasting glucose which also carry adverse cardiovascular risk. To date a few common genetic variants have been reliably associated with predisposition to type 2 diabetes. However, it is uncertain how these genes interact to alter insulin secretion and insulin action prior to the development of type 2 diabetes. We propose to utilize an established population-based cohort to determine how common genetic variants associated with type 2 diabetes alter the response to an oral glucose challenge in people without overt type 2 diabetes. This will enable us to understand how common variants alone or in combination alter whole-body glucose physiology and predispose to type 2 diabetes.