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Blood Letting in High-Ferritin Type 2 Diabetes

Effects on vascular reactivity

¹ Unit of Diabetes, Endocrinology and Nutrition, University Hospital of Girona "Dr Josep Trueta," Girona, Spain
² Department of Internal Medicine, University Hospital of Girona "Dr Josep Trueta," Girona, Spain

OBJECTIVE—In a recent study, iron chelation with deferoxamine led to improvement of endothelial dysfunction in patients with coronary artery disease. We tested the hypothesis that decreasing circulating iron stores might improve vascular dysfunction in patients with type 2 diabetes and increased serum ferritin concentration.

RESEARCH DESIGN AND METHODS—A total of 28 type 2 diabetic male patients with serum ferritin levels >200 ng/ml (18% of consecutive type 2 diabetic men attending our outpatient clinic) were randomized to iron depletion (three extractions of 500 ml blood at 2-week intervals; group 1A) or to observation (group 1B). C282Y mutation was absent in all patients. Vascular reactivity (high-resolution external ultrasound) was evaluated at baseline and at 4 and 12 months thereafter. The two groups of patients were matched for age, BMI, pharmacological treatment, and chronic diabetic complications.

RESULTS—Endothelium-dependent vasodilation remained essentially unchanged in both groups of patients. In contrast, the vasodilation induced by glyceryl trinitrate (GTN) improved significantly after iron depletion (P = 0.006). These changes occurred in parallel to decreases in transferrin saturation index and HbA_1c levels (-0.6%, P < 0.05) only in group 1A patients. The best predictor of the modifications in endothelium-independent vasodilation was the change in HbA_1c levels. Changes in endothelium-independent vasodilation also correlated with the change in serum ferritin (r = -0.45, P = 0.04). At 12 months, transferrin saturation index and GTN-induced vasodilation returned to values similar to those at baseline in both groups of subjects.

CONCLUSIONS—Iron depletion improves vascular dysfunction in type 2 diabetic patients with high ferritin concentrations. The mechanisms by which these changes occur should be further investigated.

Abbreviations: CV, coefficient of variation • GTN, glyceryl trinitrate • MDA, malondialdehyde • NO, nitric oxide

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