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BLOOD LETTING AMELIORATES INSULIN SENSITIVITY AND SECRETION IN PARALLEL TO REDUCE LIVER IRON IN CARRIERS OF HFE GENE MUTATIONS.

Transfusion Medicine, and "SanFilippo Neri" Hospital, Rome
²Hepatology Unit, "SanFilippo Neri" Hospital, Rome
¹Section of Diabetes, Endocrinology and Nutrition, University Hospital, Girona, Spain
³Dept. Internal Medicine, Catholic University, Rome
⁴Dept. of Hepato-Gastroenterology and Nutrition "Bambino Gesù" Hospital and Research Institute; Rome, Italy

melaniamanco{at}tiscali.it

ABSTRACT

Objective: To clarify the pathogenesis of diabetes associated with mutations of the haemochromatosis gene (HFE), 17 carriers, 9 with normal glucose tolerance (NGT) and 8 with diabetes (DM) were evaluated in an interventional trial.

Design and methods: At enrolment and after 2-year blood letting period, euglycemic-hyperinsulinemic-clamp (EHC), oral glucose tolerance test (OGTT), liver histology (NAS-score) and iron content (LIC) were assessed.

Results: NGT had significantly higher baseline insulin sensitivity (P0.001), secretion and insulinogenic index (IGI, calculated from the OGTT) (P0.0001 for both), lower LIC (P=0.004) and NAS-score (P=0.02) than DM patients.

Baseline LIC correlated negatively with insulin secretion (NGT r₀=–0.676; P0.0001; DM r₀=–0.589; P=0.02); insulin sensitivity (M value) (NGT r₀=–0.597; P=0.009; DM r₀=–0.535; P=0.03); and positively with NAS (DM r₀=0.649; P=0.007) and triglycerides (NGT r₀=0.563; P=0.015).

At month 24, circulating iron was reduced by 179±26 % in NGT and 284±54% in DM patients. Insulin secretion (NGT by 20±4%; DM 33±7%) and insulin sensitivity (25±5% NGT; 18±3% DM) increased. LIC decreased in both groups (by 126±42% and 61±13%), and NAS-score ameliorated (NGT 65.1±6.5 vs. 38.1±6.83; P0.0001; DM 2.1±10.7 vs. 69.9±10; P0.0001).

Conclusions: Iron depletion ameliorates insulin secretion and sensitivity in NGT and DM carriers of HFE gene mutations. This occurs in parallel to decreased LIC and improved NAS-score. These results would justify glucose tolerance testing and prophylactic iron depletion in asymptomatic carriers too.

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This article has been cited by other articles:

				L. Valenti, P. Dongiovanni, A. L. Fracanzani, and S. Fargion Bloodletting Ameliorates Insulin Sensitivity and Secretion in Parallel to Reducing Liver Iron in Carriers of HFE Gene Mutations: Response to Equitani et al. Diabetes Care, March 1, 2008; 31(3): e18 - e18. [Full Text] [PDF]

				M. Manco, G. Mingrone, V. Nobili, and F. Equitani Bloodletting Ameliorates Insulin Sensitivity and Secretion in Parallel to Reducing Liver Iron in Carriers of HFE Gene Mutations: Response to Valenti et al. Diabetes Care, March 1, 2008; 31(3): e19 - e19. [Full Text] [PDF]