Genetics and type 2 diabetes in youth

The rapid increase in the population prevalence of type 2 diabetes mellitus (T2DM) in youth can only be explained by changes in lifestyle. However, even when most members of a population have changed their lifestyle, only a minority of children develop diabetes, and genetic factors are important in determining which children are affected. Support for the role of genetic factors comes from epidemiological evidence that diabetes in youth is most common in high diabetes prevalence racial groups, in subjects with a strong family history, and in girls. Defining the genes predisposing to T2DM is extremely difficult as there are multiple genes involved each contributing only a small amount and lifestyle factors play a large role. Defining the molecular genetics of T2DM in youth is even harder because in addition to the low number of subjects, there is also the ethnic heterogeneity of the subjects and the lack of robust diagnostic criteria. Recently, there has been considerable progress in defining the predisposing genes for adults with T2DM using thousands of cases and controls and a collaborative genome-wide approach. Similar numbers will be needed to assess if the genes found in adults also predispose to T2DM of youth and this will require large multi-center studies. Progress to date in the molecular genetics of T2DM in youth is limited to one population, the Oji-Cree Native Canadians, where the private variant - G319S - a variant of HNF1A strongly predisposes to diabetes in children as well as in adults.