Abstract

Aims. Growth Differentiation Factor-15 (GDF-15) has been suggested as one of the regulators of hepcidin, an important regulatory peptide for iron deposition. Current data is conflicting about the relationship between hepcidin and disorders of glucose metabolism. We aimed to investigate serum hepcidin and GDF-15 concentrations and their associations with each other, in nonanemic subjects with impaired glucose tolerance (IGT) in comparison with the nonanemic subjects with normal glucose tolerance (NGT). Methods. Thirty-seven subjects with IGT and 32 control subjects with NGT, who were age-, gender-, and body mass index- (BMI-) matched, were included in the study. Results. Serum GDF-15 levels were significantly higher in IGT compared to NGT. There were no differences in hepcidin, interleukin-6, and high sensitive C-reactive protein levels between the groups. We found a positive correlation between GDF-15 and hepcidin levels. There were also positive correlations between GDF-15 and age, uric acid, creatinine, and area under the curve for glucose (AUC-G). Hepcidin was correlated positively with ferritin levels. In the multiple regression analysis, GDF-15 concentrations were independently associated with age, uric acid, and AUC-G. Conclusions. Impaired glucose tolerance is associated with increased GDF-15 levels even in the absence of anemia, but the levels of hepcidin are not significantly altered in prediabetic state.

Highlights

  • High iron concentrations have been suggested to be associated with subclinical inflammation and increased oxidative stress in type 2 diabetes mellitus (T2DM) [1]

  • We demonstrated that serum GDF15 concentrations are increased in nonanemic subjects with impaired glucose tolerance compared to subjects with normal glucose tolerance

  • Hepcidin has a key role in the iron metabolism and elevated hepcidin levels were shown to be associated with chronic iron overload, especially chronic disease anemia [5]

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Summary

Introduction

High iron concentrations have been suggested to be associated with subclinical inflammation and increased oxidative stress in type 2 diabetes mellitus (T2DM) [1]. A positive association between fasting glucose and insulin levels and chronic iron deposition has been reported in a population study [2]. Alterations in hepcidin levels have been reported in chronic diseases with iron deposition [4, 5]. There are a growing number of studies targeting the possible role of hepcidin in the pathogenesis of insulin resistance and related diseases [6,7,8]. Decreased or unchanged hepcidin concentrations have been found in patients with polycystic ovary and metabolic syndrome [9,10,11]. In patients with T2DM, some studies have reported decreased circulating hepcidin levels while others showed no change [10, 12, 13]. To the best of our knowledge, there is no data regarding hepcidin concentrations in subjects with impaired glucose tolerance

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