Developmental origins of type 2 diabetes in aboriginal youth in Canada: it is more than diet and exercise

Type 2 diabetes mellitus (T2DM) is classically viewed as a disease of adults caused by poor nutrition, physical inactivity, and obesity. However, with increasing awareness of the heterogeneity of T2DM, new risk factors are being identified that add complexity. Some of these new risk factors have been identified in Canadian people with Aboriginal Oji-Cree heritage, a group that demonstrates one of the highest rates of T2DM in the world. This high prevalence may be due to the rapid change, over the past 50 years, away from their traditional way of life on the land. Another environmental change is the increased rate of pregnancies complicated by obesity, gestational diabetes, or T2DM, resulting in more children being exposed to an abnormal intrauterine environment. Furthermore, the Oji-Cree of central Canada possesses the unique HNF-1α G319S polymorphism associated with reduced insulin secretion. We propose that intrauterine exposure to maternal obesity and T2DM, associated with the HNF-1α G319S polymorphism, results in fetal programming that accelerates the progression of early-onset T2DM. This paper describes the evolution of T2DM in children with a focus on the Oji-Cree people over the past 25 years and the unique prenatal and postnatal gene-environment interaction causing early-onset T2DM.