Prevalence, Characteristics, and Prognostic Significance of HFE Gene Mutations in Type 2 Diabetes: The Fremantle Diabetes Study

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.

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Typical type 2 diabetes mellitus and HFE gene mutations: a population-based case - control study

Human Molecular Genetics ◽

10.1093/hmg/ddg149 ◽

2003 ◽

Vol 12 (>12) ◽

pp. 1361-1365 ◽

Cited By ~ 32

Author(s):

D. J. Halsall

Keyword(s):

Diabetes Mellitus ◽

Case Control Study ◽

Gene Mutations ◽

Population Based ◽

Case Control ◽

Hfe Gene ◽

Typical Type ◽

Hfe Gene Mutations ◽

Control Study

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Iron Depletion Improves Glycemic Control in Poorly Controlled Type 2 Diabetic Patients with Iron Overload and Negative Main HFE-Gene Mutations

Journal of Diabetes Mellitus ◽

10.4236/jdm.2015.53020 ◽

2015 ◽

Vol 05 (03) ◽

pp. 164-172 ◽

Cited By ~ 1

Author(s):

Adel A. Mahmoud ◽

Adel A. Elazab Elged ◽

Rasha A. Elgamal ◽

Abdelhady M. Hamada

Keyword(s):

Glycemic Control ◽

Iron Overload ◽

Gene Mutations ◽

Hfe Gene ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Iron Depletion ◽

Hfe Gene Mutations ◽

Type 2 Diabetic

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Dysmetabolic iron overload syndrome and its relationship with HFE gene mutations and with liver steatosis

Digestive and Liver Disease ◽

10.1016/j.dld.2020.04.001 ◽

2020 ◽

Vol 52 (6) ◽

pp. 683-685

Author(s):

Agustín Castiella ◽

Iratxe Urreta ◽

Eva Zapata ◽

MªDolores de Juan ◽

José Mª Alústiza ◽

...

Keyword(s):

Iron Overload ◽

Liver Steatosis ◽

Gene Mutations ◽

Hfe Gene ◽

Hfe Gene Mutations

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Are “Hemochromatosis gene” mutations a risk factor for type 2 diabetes?

Gastroenterology ◽

10.1016/s0016-5085(08)81131-6 ◽

2001 ◽

Vol 120 (5) ◽

pp. A227

Author(s):

Nicholas J. Shaheen ◽

Lawrence M. Silverman ◽

Laura B. Lawrence ◽

Elizabeth M. Rohlfs ◽

John B. Buse ◽

...

Keyword(s):

Type 2 Diabetes ◽

Risk Factor ◽

Gene Mutations ◽

Hemochromatosis Gene

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HFE gene mutations in liver cirrhosis and hepatocellular carcinoma

Journal of Hepatology ◽

10.1016/s0168-8278(00)80918-6 ◽

2000 ◽

Vol 32 ◽

pp. 154

Author(s):

G. Sebastiani ◽

L. Benvegnù ◽

P. Angeli ◽

P. Pontisso ◽

A. Gatta ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Gene Mutations ◽

Hfe Gene ◽

Hfe Gene Mutations

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“CHANGES IN THE NERVOUS SYSTEM IN PATIENTS WITH DIABETES MELLITUS TYPE 2 WITH NEPHROPATHY AND PROGNOSTIC SIGNIFICANCE OF NEUROMARKERS OF BRAIN INJURY. LITERATURE REVIEW"

EurasianUnionScientists ◽

10.31618/esu.2413-9335.2021.1.89.1437 ◽

2021 ◽

pp. 3-8

Author(s):

Yu. Urmanova ◽

A. Holikov

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Nervous System ◽

Type 2 Diabetes Mellitus ◽

Biochemical Markers ◽

Prognostic Significance ◽

Functional Changes ◽

Neurospecific Proteins

THE PURPOSE OF THE STUDY is to carry out an analysis of the literature evaluating diabetic encephalopathy by determining neuromarkers. MATERIAL AND METHODS. In this article, the authors analyzed the literature on the role of neuromarkers in patients with type 2 diabetes mellitus undergoing program hemodialysis. RESEARCH RESULTS. Among biochemical markers, the determination of the level of neurospecific proteins is actively being investigated. The main part of them is autoantigens, entering the bloodstream, can cause the appearance of autoantibodies, which, when the blood-brain barrier is impaired, enter the brain from the blood vessel and cause morphological changes, destructive processes in neurons, as well as the development of nonspecific acute-phase reactions like edema or inflammation. Biomarker studies for the diagnosis of various brain lesions have been under way for more than 20 years, but at present no ideal biomarker has been found. Among biochemical markers, the determination of the level of neurospecific proteins is being actively studied. In patients with type 2 diabetes mellitus undergoing hemodialysis, this issue is also relevant in view of the frequent vascular cerebrovascular complications, but few studies have been conducted. CONCLUSIONS. All of the above emphasizes the need to identify the features of clinical and functional changes in the nervous system in patients with type 2 diabetes mellitus receiving program hemodialysis and to evaluate the prognostic value of neuromarkers in early detection of the degree of brain damage.

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