Low Hepcidin in Type 2 Diabetes Mellitus: Examining the Molecular Links and Their Clinical Implications

Vela, Driton; Sopi, Ramadan; Mladenov, Mitko

doi:10.1016/j.jcjd.2017.04.007

Cited by 14 publications

(19 citation statements)

References 105 publications

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“…Overall, 45% of the included studies (n ¼ 5) reported on iron levels [5,10,11,25,27]. Of these, 3 studies [5,10,41] reported comparable iron levels between T2D and controls. The other 2 studies [11,25] described elevated levels in T2D when compared to controls (Table 1).…”

Section: Surrogate Markers Of Hepcidinmentioning

confidence: 99%

Body weight and its influence on hepcidin levels in patients with type 2 diabetes: A systematic review and meta-analysis of clinical studies

Ndevahoma

Mukesi

Dludla

et al. 2021

Heliyon

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Introduction: Iron profiles in patients with type 2 diabetes (T2D) are inconsistent. In this study, we assessed the levels of hepcidin, a regulatory protein involved in iron homoeostasis, in patients with T2D. We further evaluated the surrogate markers of hepcidin action, particularly those associated with erythropoiesis. Methods: This systematic review and meta-analysis was reported following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. We searched for relevant studies in electronic databases from inception until 31 October 2020 without any language restriction. The random effects model was used to calculate effect estimates, and outcomes were reported as either standardised mean difference (SMD) or mean differences (MD), 95 percent confidence interval (95% CI). Results: Eleven studies involving 2 620 participants were included in this study. Patients with T2D had a slight increase in hepcidin levels when compared to controls SMD: 0.07 [95% CI:-0.30, 0.44]. The subgroup analysis showed that studies involving patients with T2D who were overweight reported elevated hepcidin levels SMD: 0.35 [95% CI: 0.07, 0.62] whilst those with grade I obesity described reduced levels SMD:-0.42 [95% CI:-1.21, 0.38]. All T2D patients had low levels of haemoglobin MD:-0.23 g/dl [95% CI:-0.46,-0.01] irrespective of body weight. Conclusion: The levels of hepcidin are altered in patients with T2D and are disproportionately influenced by weight. Moreover, patients with T2D present with subclinical anaemia despite elevated iron stores. The regulation of hepcidin in patients with T2D is dependent on several factors and vary greatly, thus its sole use in clinical settings may be less beneficial.

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Section: Surrogate Markers Of Hepcidinmentioning

confidence: 99%

Body weight and its influence on hepcidin levels in patients with type 2 diabetes: A systematic review and meta-analysis of clinical studies

Ndevahoma

Mukesi

Dludla

et al. 2021

Heliyon

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“…15 Therefore, the adverse effect of iron overload should not be underestimated. Mechanically, oxidative stress induced by iron overload can gradually damage the function of islet cells and lead to disorder of glucose metabolism 16,17 It is still necessary to clarify the relative risk of iron supplementation for iron-replete pregnant women. 18 How to carry out iron supplementation during pregnancy is an important issue worthy of attention.…”

Section: Hb Concentration Is a Reflection Of Iron Load In Vivomentioning

confidence: 99%

Hemoglobin concentration and iron supplement during pregnancy were associated with an increased risk of gestational diabetes mellitus

Shen

Xing

et al. 2020

Journal of Diabetes

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Background Hemoglobin (Hb) measurement is a conventional test during perinatal visits. Hb concentration is related to iron supplement. However, studies focusing on Hb levels, iron supplement, and pregnancy outcomes are scarce. This study aimed to determine whether Hb levels and iron supplement were associated with the risk of gestational diabetes mellitus (GDM). Methods A running hospital‐based cohort was conducted from August, 2011. The demographic data and medical information were collected individually through questionnaires and patient medical records. Multiple linear regression was applied for the association between Hb levels, iron supplement, and blood glucose. Multiple logistic regression was used for evaluating odds ratios between Hb levels, iron supplement, and GDM. Results Hb levels during first (T1) and second trimester (T2) of pregnancy were significantly and positively associated with blood glucose and GDM risk. After adjusting for age, prepregnancy body mass index, and other risk factors, pregnant women with Hb ≥ 11 g/dL and iron supplement had higher postprandial blood glucose at 1 hour (Hb ≥ 11 g/dL in T2 and iron supplement in T1: β = 0.860，P = <0.001; Hb ≥ 11 g/dL in T2 and iron supplement in T2: β = 0.960，P < 0.001; Hb ≥ 11 g/dL in T1 and iron supplement in T2: β = 1.133, P = 0.033) and GDM risks (odds ratio [OR] = 1.53, 95% confidence interval [CI]: 1.05‐2.24; OR = 1.92, 95% CI: 1.13‐3.35; OR = 2.15, 95% CI: 1.07‐4.34, respectively), compared with those with Hb < 11 g/dL and without iron supplement. Conclusion High Hb concentration and iron supplements without anemia increased postprandial blood glucose and risks for GDM. It indicates that pregnant women with good Hb levels should not be advised to take iron supplements during pregnancy.

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“…Increased levels of VLDL particles among others are considered also a hallmark of affected lipoprotein metabolism in pre-diabetes [ 27 ]. Likewise, increased serum ferritin has been reported in relation to altered levels of VLDL-TG as well as HDL- and LDL-cholesterol [ 28 , 29 ], while serum ferritin is also increasingly recognized as marker for metabolic disease, in particular T2DM [ 6 , 7 ]. In line with this notion, we observed positive associations of serum ferritin with BCAAs and related intermediates which were shown to predict incident T2DM or fatty liver disease in numerous population-based studies [ 30 , 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, less is known about the metabolic consequences of alterations in iron metabolism. Previous studies [ 6 , 7 ] suggested surrogates of iron metabolism, for example, ferritin, as markers of incident type 2 diabetes mellitus (T2DM) and disturbances of iron metabolism manifested as anaemia were associated with T2DM. Further, an increase in serum ferritin was associated with increased oxidation of lipoprotein particles among subjects from the general population [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Fingerprints of Iron Parameters among a Population-Based Sample

et al. 2018

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Iron deficiency is the most frequent deficiency disease and parameters of iron metabolism appear to be linked to major metabolic and cardiovascular diseases. We screened a large set of small molecules in plasma for associations with iron status among apparently healthy subjects to elucidate subclinical profiles which may provide a link between iron status and onset of diseases. Based on mass spectrometry and nuclear magnetic resonance spectroscopy we determined 613 plasma metabolites and lipoprotein subfractions among 820 apparently healthy individuals. Associations between ferritin, transferrin, haemoglobin and myoglobin and metabolite levels were tested by sex-specific linear regression analyses controlling for common confounders. Far more significant associations in women (82 out of 102) compared to men became obvious. The majority of the metabolites associated with serum ferritin and haemoglobin in women comprising fatty acid species, branched-chain amino acid catabolites and catabolites of heme. The latter was also obvious among men. Positive associations between serum transferrin and VLDL and IDL particle measures seen in women were observed in men with respect to serum ferritin. We observed a sexual-dimorphic fingerprint of surrogates of iron metabolism which may provide a link for the associations between those parameters and major metabolic and cardiovascular disease.

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Low Hepcidin in Type 2 Diabetes Mellitus: Examining the Molecular Links and Their Clinical Implications

Cited by 14 publications

References 105 publications

Body weight and its influence on hepcidin levels in patients with type 2 diabetes: A systematic review and meta-analysis of clinical studies

Body weight and its influence on hepcidin levels in patients with type 2 diabetes: A systematic review and meta-analysis of clinical studies

Hemoglobin concentration and iron supplement during pregnancy were associated with an increased risk of gestational diabetes mellitus

Molecular Fingerprints of Iron Parameters among a Population-Based Sample

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