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Total mortality by elevated transferrin saturation in patients with diabetes.

ABSTRACT: OBJECTIVE: It 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 METHODS: Cohort 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%. RESULTS: In 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. CONCLUSIONS: Increased 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.

SUBMITTER: Ellervik C

PROVIDER: S-EPMC3747880 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Total mortality by elevated transferrin saturation in patients with diabetes.

Ellervik Christina C Andersen Henrik Ullits HU Tybjærg-Hansen Anne A Frandsen Merete M Birgens Henrik H Nordestgaard Børge G BG Mandrup-Poulsen Thomas T

Diabetes care 20130625 9

<h4>Objective</h4>It 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.<h4>Research design and methods</h4>Cohort 1 in ...[more]

PMID: 23801727

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Project description:BackgroundOptimal iron levels in patients on hemodialysis are currently unknown, and a higher level than that for the healthy population is usually set for such patients considering the use of erythropoiesis-stimulating agents or the occurrence of chronic inflammation. However, excessive iron causes oxidative stress and impairment of its utilization by cells. Therefore we investigated the relationship between hemoglobin (Hb) level and iron status in hemodialysis patients to identify the optimal iron levels for patients undergoing hemodialysis.MethodsA total of 208 outpatients on maintenance hemodialysis were followed up between July 2006 and June 2007. Men accounted for 64.9% cases [mean age, 59.3 ± 13.1 years and median dialysis history, 7.7 (3.6-13.2) years], and diabetic nephropathy accounted for 25.0% cases. Hemoglobin level was measured twice a month and serum ferritin, serum iron, and total iron-binding capacity were measured once a month. The doses of recombinant human erythropoietin and low-dose iron supplement were adjusted to maintain a hemoglobin level of 10-11 g/dL, according to the guidelines of the Japanese Society for Dialysis Therapy. Hepcidin was measured at baseline. Using the mean values for 1-year period, the relationships among hemoglobin, serum ferritin levels, and transferrin saturation levels were investigated based on a receiver operating characteristic curve and a logistic regression model. In addition, the correlations among serum ferritin, transferrin saturation, and hepcidin levels were analyzed by Pearson product-moment correlation coefficient and linear regression model.ResultsBy receiver operating characteristic curve, the cutoff point of serum ferritin and transferrin saturation levels with a hemoglobin ?10 g/dL showed <90 ng/mL (sensitivity: 69.1%, specificity: 72.1%, p < 0.001) and ?20% (sensitivity: 77.6%, specificity: 48.8%, p = 0.302). Upon logistic regression model analysis with a hemoglobin ?10 g/dL as the endpoint, the analysis of odds ratios relative to a group with serum ferritin ?90 ng/mL and transferrin saturation <20% revealed that the group with serum ferritin <90 ng/mL and transferrin saturation ?20% had the highest ratio: 46.75 (95% confidence interval: 10.89-200.70, p < 0.001). In Pearson product-moment correlation coefficient, hepcidin showed a strong positive correlation with serum ferritin [r = 0.78 (95% confidence interval: 0.72-0.83, p < 0.001)] and a weak positive correlation with transferrin saturation [r = 0.18 (95% confidence interval: 0.04-0.31, p = 0.010)]. In the multivariable analyses of the linear regression model, a positive relationship was shown between hepcidin and serum ferritin [?-coefficient of 0.30 (95% confidence interval: 0.27-0.34, p < 0.001)]; however, no relationship was shown with transferrin saturation [?-coefficient of 0.09 (95% confidence interval: -0.31-0.49, p = 0.660)].ConclusionsIn this study, the iron status of serum ferritin <90 ng/mL and transferrin saturation ?20% was optimal in hemodialysis patients receiving recombinant human erythropoietin for anemia therapy. This result indicates that the threshold values for the optimal iron status may be lower than those currently recommended in iron-level management guideline.

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Total mortality by elevated transferrin saturation in patients with diabetes.

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Total mortality by elevated transferrin saturation in patients with diabetes.

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