Prevalence, characteristics and prognostic significance of HFE gene mutations in type 2 diabetes: The Fremantle Diabetes Study

Abstract

Objective– To examine the relationship between iron status, hereditary hemochromatosis (HFE) gene mutations, and clinical features and outcomes of type 2 diabetes in a well-characterized, representative sample of community-based patients.

Research Design and Methods– HFE genotype data were available for 1245 type 2 patients from the longitudinal observational Fremantle Diabetes Study (FDS), representing 96.2% of the total FDS type 2 cohort. Data were collected at recruitment between 1993 and 1996, and annually until end-June 2001. Hospitalization and mortality data were available to end-June 2006. The presence of the C282Y HFE mutation was determined in all subjects and H63D in C282Y heterozygotes. Fasting serum iron, transferrin and ferritin were measured in all C282Y homozygotes, C282Y/H63D heterozygotes and 286 randomly-selected wild-type subjects. Multiple logistic regression analysis was performed to determine independent baseline associates of prevalent complications (myocardial infarction, cerebrovascular disease, retinopathy, neuropathy and nephropathy), and Cox proportional hazards modeling to determine predictors of incident complications and mortality.

Results– Although there were expected positive associations between HFE gene mutations and serum iron and transferrin saturation, there were no independent positive associations between HFE gene status and either microvascular or macrovascular complications in cross-sectional and longitudinal analyses. HFE gene status did not independently predict cardiac or all-cause mortality. Measures of iron metabolism including serum ferritin were not associated with combined microvascular or macrovascular endpoints.

Conclusions– Directed screening for iron overload and/or HFE mutations appears unwarranted in patients with type 2 diabetes.