Abstract

BackgroundTestosterone plays an important role in the regulation of glucose metabolism. While earlier studies have shown that it has a protective effect in males, unfavorable effects of testosterone on glucose metabolism have been reported in females; however, whether there is a sex-specific relationship between testosterone and glucose metabolism in patients with prediabetes has not been investigated in detail hitherto.MethodsThis cross-sectional analysis investigated 423 males and 287 females with diagnosed prediabetes. Detailed assessment of their metabolic profiles was performed, including a 2‑h oral glucose tolerance test (OGTT), HbA1c levels, calculation of insulin resistance with homeostatic model assessment for insulin resistance (HOMA-IR), assessment of lipid metabolism, anthropometric parameters and the fatty liver index (FLI). By using Spearman’s correlation test, we investigated the sex-specific relationship between testosterone and metabolism in the prediabetic individuals.ResultsIn the present study, prediabetic females (mean age 58.6 years, confidence interval [CI: 57.6 y; 59.5 y]) were characterized by lower fasting plasma glucose levels (104.2 mg/dl [CI: 103.0 mg/dl; 105.4 mg/dl] vs. 106.9 mg/dl [CI: 106.0 mg/dl; 107.8 mg/dl]) and a lower FLI (49.5 [CI: 45.7; 53.2] vs. 58.8 [CI: 55.8; 61.8]), but presented with a higher risk of developing manifest type 2 diabetes in the next 10 years (FINDRISK score: 17.6 [CI: 17.1; 18.1] vs. 16.1 [CI: 15.7; 16.5]) when compared to prediabetic males (mean age: 58.04 years [CI: 57.0 y; 59.1 y]). Testosterone was negatively related to insulin resistance (HOMA-IR: Spearman’s ρ: −0.33, p < 0.01), 2‑h stimulated glucose levels during the OGTT (ρ = −0.18, p < 0.01), HbA1c levels (ρ = −0.13, p < 0.05), FLI and BMI in prediabetic males; however, no relationship between testosterone and metabolic parameters could be found in prediabetic females.ConclusionThe increase of testosterone levels in males was related to a more favorable glucose metabolism, including lower HbA1c, lower stimulated glucose levels and higher insulin sensitivity; however, in prediabetic females, testosterone was not related to glucose metabolism.

Highlights

  • In recent years, the prevalence of type 2 diabetes mellitus (T2DM) has been steadily increasing and is predicted to rise even further worldwide by 2045

  • Testosterone was negatively related to insulin resistance (HOMA-IR: Spearman’s ρ: –0.33, p < 0.01), 2-h stimulated glucose levels during the oral glucose tolerance test (OGTT) (ρ = –0.18, p < 0.01), HbA1c levels (ρ = –0.13, p < 0.05), fatty liver index (FLI) and BMI in prediabetic males; no relationship between testosterone and metabolic parameters could be found in prediabetic females

  • Increase in testosterone levels is related to a lower risk of conversion of prediabetes to manifest diabetes in

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Summary

Introduction

The prevalence of type 2 diabetes mellitus (T2DM) has been steadily increasing and is predicted to rise even further worldwide by 2045. Low testosterone and sex hormone binding globulin (SHBG) levels in men can be linked to increased visceral fat content [6]. The pathophysiological mechanisms behind these sex-specific differences are not entirely clear to date; one of the main reasons for the higher occurrence of increased FPG levels in men may be the elevated hepatic glucose output as well as impaired early insulin secretion. Women more often suffer from impaired glucose tolerance (IGT) and an explanation for these sex-specific differences may be the slower duration of gastric emptying and intestinal glucose absorption in women [9]; especially the influence of sex hormones on disturbances of glucose metabolism in prediabetic patients is, overall, an unexplored area. This study aimed to investigate the relationship between testosterone and glucose metabolism in prediabetic patients in a sex-specific manner

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