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J Clin Endocrinol Metab. 2009 Mar;94(3):982-8. doi: 10.1210/jc.2008-1211. Epub 2008 Dec 30.

Study of circulating prohepcidin in association with insulin sensitivity and changing iron stores.

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  • 1Department of Diabetes, Endocrinology and Nutrition, University Hospital of Girona Dr Josep Trueta and CIBER Fisiopatología de Obesidad y Nutrición CB06/03/010, 17007 Girona, Spain. jmfernandezreal.girona.ics@gencat.cat

Abstract

BACKGROUND:

Liver synthesizes hepcidin in response to iron overload, leading to down-regulation of duodenal iron absorption. The pathophysiology of type 2 diabetes is associated with increased iron stores. We aimed to study circulating prohepcidin in association with insulin sensitivity and parameters of glucose and iron metabolism.

METHODS:

Serum prohepcidin was evaluated in three cohorts: 1) a cross-sectional study (cohort 1, men from the general population; n = 135); 2) after decreasing iron stores in men with "high-ferritin" type 2 diabetes (cohort 2; n = 13); and 3) after decreasing iron stores in men carrying HFE gene mutations (cohort 3; n = 16). Insulin sensitivity was measured using either the minimal model or the clamp technique.

RESULTS:

Circulating prohepcidin correlated significantly with glycated hemoglobin (P < 0.0001), fasting glucose (P = 0.002), triglycerides (P = 0.007), high-density lipoprotein-cholesterol (P = 0.01), ferritin (P = 0.01), and soluble transferrin receptor concentration (P = 0.001) in subjects from cohort 1. Prohepcidin decreased significantly after iron depletion in patients with type 2 diabetes (P = 0.04) (cohort 2) and in carriers of HFE gene mutations (P = 0.03) (cohort 3). In the latter subjects, the change in serum prohepcidin after iron depletion was associated with the change in both fasting glucose transferrin (r = 0.58; P = 0.02) and saturation (r = 0.68; P = 0.005). The changes in insulin sensitivity were associated with those of liver iron content (r = -0.64; P = 0.007) and with those of serum prohepcidin (r = -0.50; P = 0.04) (cohort 3).

CONCLUSIONS:

These associations suggest that circulating prohepcidin concentration is pathophysiologically associated with parameters of glucose and iron metabolism. A failure to increase prohepcidin synthesis is hypothesized to contribute to iron-induced disorders of glucose metabolism.

PMID:
19116239
[PubMed - indexed for MEDLINE]
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