Total Mortality by Elevated Transferrin Saturation in Patients With Diabetes

Abstract

OBJECTIVEIt is not known to what extent iron overload predicts prognosis in patients with diabetes after diagnosis or whether iron overload is a risk factor independent of the HFE genotype. We investigated total and cause-specific mortality according to increased transferrin saturation (≥50 vs. <50%), whether mortality is driven by the HFE genotype, and whether early measurement of transferrin saturation helps to predict mortality outcome.RESEARCH DESIGN AND METHODSCohort 1 included patients with late-onset type 1 diabetes (n = 716) with a cross-sectional measurement of transferrin saturation and HFE genotype. Cohort 2 included consecutively recruited patients with any diabetes (n = 6,120), transferrin saturation measurement at referral, and HFE genotype if transferrin saturation was above 50%.RESULTSIn cohort 1, the hazard ratio for total mortality was 2.3 (95% CI 1.3–3.9; P = 0.002) and for cause-specific mortality by neoplasms was 5.8 (2.4–14; P = 0.00007) in patients with transferrin saturation ≥50 vs. <50%. Excluding genotypes C282Y/C282Y and C282Y/H63D gave similar results. The hazard ratio for total mortality was 4.0 (1.2–13; P = 0.01) and for cause-specific mortality by neoplasms was 13 (3.6–49; P = 0.0001) in patients with C282Y/C282Y versus wild type. In cohort 2, total mortality was not different in patients with transferrin saturation ≥50 vs. <50%. In patients with late-onset type 1 diabetes and transferrin saturation ≥50%, the hazard ratio for total mortality was 0.4 (0.2–0.9; P = 0.03) in cohort 2 versus cohort 1.CONCLUSIONSIncreased transferrin saturation and HFE genotype C282Y/C282Y predict total mortality in patients with late-onset type 1 diabetes, and increased transferrin saturation after diagnosis is an independent risk factor. Early measurement of transferrin saturation in these patients leading to early intervention improves life expectancy.