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

Abstract

Summary Background Testosterone 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. Methods This 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. Results In 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. Conclusion The 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.

Examining the associations between testosterone and biomarkers as men age

“…The present study found a significant inverse association between insulin and both TT and SHBG, even after adjusting for other variables. This finding is consistent with several cross-sectional studies (Kurniawan et al, 2020;Leutner et al, 2022;Osuna et al, 2006;Pasquali et al, 1995;Phillips et al, 2003) and an 8-year longitudinal study (Oh et al, 2002), which found testosterone concentrations to be inversely associated with insulin concentrations over the duration of the study. Even though insulin is not a clinical condition, elevated insulin concentrations, hyperinsulinemia, may be indicative of IR and the future development of metabolic syndrome (Wilcox, 2005) (Ling et al, 2016) (Sung et al, 2011).…”

“…The present study found a significant inverse association between the 2-hour OGTT results and TT. This result is supported by several studies (Leutner et al, 2022;Wittert et al, 2021). An OGTT predicts insulin sensitivity with reasonable accuracy (Stumvoll et al, 2001) and may assist with the prediction of T2DM development (Hayashi et al, 2013), one of the comorbidities associated with obesity (Golay & Ybarra, 2005).…”

Hypogonadotropic Hypogonadism in Diabesity: Pathogenic Factors and Therapeutic Implications

“… 6 , 7 An Austrian study has also recently confirmed a relationship between testosterone and insulin sensitivity and related metabolic indices in prediabetic males. 15 Clearly, therefore, HH predisposes individuals to an insulin-resistant state and testosterone restores insulin sensitivity and can potentially reverse type 2 diabetes and prediabetes. 6 , 15–17 …”

“… 15 Clearly, therefore, HH predisposes individuals to an insulin-resistant state and testosterone restores insulin sensitivity and can potentially reverse type 2 diabetes and prediabetes. 6 , 15–17 …”