Synergism between mutant HNF1A and the metabolic syndrome in Oji-Cree Type 2 diabetes

Aims To determine the prevalence of the metabolic syndrome in the Sandy Lake Oji‐Cree and to examine its interaction with HNF1A in association with impaired glucose tolerance and Type 2 diabetes. Methods Using data collected from the Sandy Lake Health and Diabetes Project (1993–1995), the presence or absence of the metabolic syndrome was determined in 515 Oji‐Cree subjects, ≥ 18 years of age. In the original study, fasting plasma analytes were measured, a 75‐g oral glucose tolerance test was administered, and subjects were genotyped for HNF1A G319S. Results The unadjusted prevalence of the metabolic syndrome in the Oji‐Cree adults was 29.9%. The adjusted odds ratio (OR) and 95% confidence interval for Type 2 diabetes among subjects who carried the HNF1A G319S mutation and had the modified metabolic syndrome (excluding hyperglycaemia) was 20.3 (6.94, 59.6). Adjusted ORs for Type 2 diabetes for subjects with either the HNF1A G319S mutation alone or the modified metabolic syndrome alone were 5.56 (2.85, 10.9) and 4.84 (2.53, 9.27), respectively. The risk of having impaired glucose tolerance was not influenced by the presence of either factor. Conclusions The risk of Type 2 diabetes was similar (approximately five‐fold increased) for subjects with either the presence of the modified metabolic syndrome or the private HNF1A G319S mutation. Interestingly, when present in combination, the two independent risk factors appeared to act synergistically to confer an even greater increased risk of Type 2 diabetes.