Raised circulating soluble growth differentiation factor 15 is negatively associated with testosterone level in hypogonadic men with type 2 diabetes

Epidemiological studies consistently show that decreases in serum testosterone level are observed more frequently in men with type 2 diabetes mellitus (T2DM), while clinical investigations have demonstrated that an increased level of circulating growth differentiation factor-15 (GDF-15) are also related closely to T2DM. The aim of this study was to examine the potential relationship between serum GDF-15 levels and hypogonadism in Chinese male patients with T2DM.A total of 305 T2DM men were recruited between July 2020 and August 2021. GDF-15 and total testosterone concentrations were quantified by an enzyme-linked immunosorbent assay and LC/MS mass spectrometry, respectively. Multiple linear regression analysis, logistic regression, and restricted cubic splined models were used to examine the correlation between GDF-15 levels and hypogonadism in these patients.When compared with T2DM patients without hypogonadism circulating GDF-15 levels were significantly higher in the hypogonadism group [1081.83 (746.79,1539.94) versus 779.49 (548.46,1001.27), p < 0.001] and were associated positively with hypogonadism in unadjusted and fully adjusted multivariate regression models (p < 0.01). The fully adjusted regression coefficients with 95% confidence intervals for circulating GDF-15 and testosterone deficiency were -1.795 (-2.929, -0.661). Serum GDF-15 levels were also associated positively with testosterone deficiency in each logistic regression model (p < 0.05), while after adjustment for all risk factors, the same findings were obtained in the restricted cubic splined models (p < 0.01).In hypogonadal men with T2DM, an elevated serum GDF-15 level is associated negatively with serum testosterone concentration. GDF-15 may be a novel cytokine related to T2DM men with hypogonadism.