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

Jose Manuel Fernandez-Real, Francesco Equitani, José María Moreno, Melania Manco, Francisco Ortega, Wifredo Ricart

Research output: Contribution to journalArticle

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 Iipoprotein-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 pathophysi-ologically 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.

Original languageEnglish
Pages (from-to)982-988
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume94
Issue number3
DOIs
Publication statusPublished - Mar 2009

Fingerprint

Hepcidins
Insulin Resistance
Iron
Insulin
Glucose
Medical problems
Type 2 Diabetes Mellitus
Metabolism
Ferritins
Liver
Fasting
Glucose Metabolism Disorders
Serum
Genes
Mutation
Transferrin Receptors
Iron Overload
Glycosylated Hemoglobin A
Transferrin
Clamping devices

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Study of circulating prohepcidin in association with insulin sensitivity and changing iron stores. / Fernandez-Real, Jose Manuel; Equitani, Francesco; Moreno, José María; Manco, Melania; Ortega, Francisco; Ricart, Wifredo.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 94, No. 3, 03.2009, p. 982-988.

Research output: Contribution to journalArticle

Fernandez-Real, Jose Manuel ; Equitani, Francesco ; Moreno, José María ; Manco, Melania ; Ortega, Francisco ; Ricart, Wifredo. / Study of circulating prohepcidin in association with insulin sensitivity and changing iron stores. In: Journal of Clinical Endocrinology and Metabolism. 2009 ; Vol. 94, No. 3. pp. 982-988.
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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 Iipoprotein-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 pathophysi-ologically 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.",
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T1 - Study of circulating prohepcidin in association with insulin sensitivity and changing iron stores

AU - Fernandez-Real, Jose Manuel

AU - Equitani, Francesco

AU - Moreno, José María

AU - Manco, Melania

AU - Ortega, Francisco

AU - Ricart, Wifredo

PY - 2009/3

Y1 - 2009/3

N2 - 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 Iipoprotein-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 pathophysi-ologically 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.

AB - 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 Iipoprotein-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 pathophysi-ologically 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.

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