Biomarkers of body iron stores and risk of developing type 2 diabetes

Iron may contribute to the pathogenesis of type 2 diabetes mellitus (DM) by inducing oxidative stress and interfering with insulin secretion. Elevated ferritin levels are associated with increased DM risk among healthy individuals. However, it is yet unknown if ferritin predicts DM incidence among high-risk individuals with impaired glucose tolerance (IGT). Furthermore, the association between soluble transferrin receptors (sTfR), a novel marker of iron status, and DM risk has not yet been prospectively investigated in these individuals. We conducted this study to evaluate the association between baseline levels of ferritin and sTfR and the risk of developing DM among overweight and obese individuals at high risk of DM. This nested case-control study (280 cases and 280 matched controls) was conducted within the placebo arm of the Diabetes Prevention Program, is a clinical trial conducted among overweight/obese individuals with IGT. Ferritin and sTfR levels were measured by immunoturbidimetric assays. Incident DM was ascertained by annual 75-g oral glucose tolerance test and semi-annual fasting glucose. Compared with controls, cases had higher sTfR levels (3.50 +/- 0.07 vs. 3.30 +/- 0.06 mg/l; p = 0.03), but ferritin levels were not statistically different. The multivariable odds ratios (OR) and 95% confidence intervals (95% CI) for DM incidence comparing highest with the lowest quartiles of sTfR was 2.26 (1.37-4.01) (p-trend: 0.008). Modestly elevated sTfR levels are associated with increased DM risk among overweight and obese individuals with IGT. Future studies should evaluate factors determining sTfR levels and examine if interventions that lower body iron stores reduce DM incidence.