Effect of iron overload on glucose metabolism in patients with hereditary hemochromatosis
ABSTRACT Diabetes mellitus (DM) affects 30% to 60% of patients with hereditary hemochromatosis (HH). The underlying pathophysiology of DM in patients with hemochromatosis has not been fully elucidated. We studied both insulin secretion and insulin sensitivity in a cohort of patients with HH. We studied glucose metabolism in 53 newly diagnosed HH patients using a standard 75-g oral glucose tolerance test. Basal and stimulated insulin sensitivities were calculated using the quantitative insulin sensitivity check index and oral glucose insulin sensitivity index, respectively. beta-Cell function was assessed using C-peptide concentrations during the oral glucose tolerance test after adjusting for ambient insulin sensitivity. Twenty healthy subjects served as the control group. Fifteen subjects (28%) with HH had abnormal glucose tolerance (AGT). Seven (13%) had DM, and 8 (15%) had impaired glucose tolerance. As well as higher fasting glucose and glycated hemoglobin, those with AGT had a higher fasting insulin and C-peptide levels compared with those with normal glucose tolerance (NGT) (all Ps < .05). Insulin sensitivity measurements showed that the subjects in HH group with AGT were more insulin resistant than the subjects with NGT and controls subjects (P < .05). No significant changes were observed between the groups with NGT and AGT regarding hepatic insulin extraction and both indices related to insulin release in subjects with HH. Our cohort of patients with hemochromatosis and AGT had features similar to typical type 2 DM patients. These findings challenge the traditional view that DM in hemochromatosis is due primarily to iron-induced beta-cell failure.
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ABSTRACT: Several inborn errors of metabolism present with hepatic disease in the adult population•Clinical features and diagnosis of Wilson disease, alpha-1 antitrypsin deficiency, citrin deficiency, and HFE-associated hemochromatosis will be discussed•Treatment update will be presentedMolecular Genetics and Metabolism 11/2014; DOI:10.1016/j.ymgme.2014.10.011 · 2.83 Impact Factor
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ABSTRACT: Iron overload might be ascribable to hereditary or secondary causes. Hereditary hemochromatosis is the most common genetic disorder among Caucasians. In Portugal, likewise in Europe, it is more frequent in the North. Diabetes due to hereditary hemochromatosis seems to result from a decrease in insulin secretion and increase in insulin resistance. No consensus was reached on what concerns to the main mechanism. High iron intake, increased transferrin saturation and C282Y homozygosity are associated with increased risk for type 1 diabetes mellitus. It is advisable to assess iron stores in patients with diabetes mellitus, as long as an early diagnosis of iron overload may prevent subsequent complications.01/2014; DOI:10.1016/j.rpedm.2014.03.001
Article: Diabetes and Hemochromatosis.[Show abstract] [Hide abstract]
ABSTRACT: The common form of hereditary hemochromatosis is an autosomal recessive disorder most prevalent in Caucasians that results in excessive iron storage. The clinical manifestations of hemochromatosis are protean. HFE genotype, which determines the degree of iron overload and duration of disease have profound effects on disease expression. The prevalence of diabetes in this population has likely been underestimated because of studies that include a broad range of ethnicities and associating diabetes with allele frequency in spite of the decreased risk of diabetes in heterozygotes compared with homozygotes. Loss of insulin secretory capacity is likely the primary defect contributing to development of diabetes with insulin resistance playing a secondary role. Phlebotomy can ameliorate the defects in insulin secretion if initiated early. Screening a select population of individuals with type 2 diabetes may identify patients with hemochromatosis early and substantially impact individual clinical outcomes.Current Diabetes Reports 05/2014; 14(5):488. DOI:10.1007/s11892-014-0488-y · 3.38 Impact Factor