Tracking ancient pathways to a modern epidemic: diabetic end-stage renal disease in Saskatchewan aboriginal people.

BACKGROUND: Saskatchewan aboriginal people are experiencing an epidemic of type 2 diabetes (T2DM) and diabetic end-stage renal disease (DESRD). The purpose of these investigations was to study the role of the intrauterine environment in the emergence of these diseases. METHODS: Epidemiologic studies were carried out using data from the Provincial Department of Health databases, the Saskatoon Health Region obstetrical unit, the Saskatchewan Renal Transplant Program, surveys of Saskatchewan aboriginal communities, and the Canadian Organ Replacement Registry. Parameters analyzed included rates, risk factors, and outcomes of T2DM, gestational diabetes (GDM), and DESRD; birth registration information; anthropometric measurements; and human leukocyte antigen profiles. RESULTS: Aboriginal ethnicity is an independent predictor of GDM. High rates of GDM appear in remote aboriginal communities before the significant appearance of T2DM and are associated with increasing rates of high birth weight. A significant relationship between high-birth-weight rates and T2DM has strengthened over several decades. Finally, higher birth weights and older mother's age (both associated with GDM), and increased frequencies of the human leukocyte antigen-A2/DR4 and A2/DR8 haplotypes are associated with DESRD among aboriginal people. CONCLUSION: It is likely that diabetic pregnancies play a key role in the initiation, progression, and perpetuation of the T2DM epidemic among Canadian aboriginal peoples, and may additionally increase the risk for DESRD. We speculate that an ancient survival advantage that promoted caloric conservation in young women and their unborn children is now a risk factor for prepregnancy obesity, GDM, and excess fetal nutrition. Infants are often large and have an increased risk for T2DM and its complications (hefty fetal-type hypothesis).