Low serum dehydroepiandrosterone sulfate is related to diabetic retinopathy in males with type 2 diabetes mellitus

Abstract Objective Androgens are increasingly recognized as important regulators of metabolic balance and vascular integrity. However, their relationship with diabetic retinopathy (DR) remains incompletely defined and appears to differ by sex. The present study aimed to examine the associations between circulating levels of total testosterone (TT), dehydroepiandrosterone sulfate (DHEAS), and androstenedione (ASD) and DR risk among individuals with type 2 diabetes mellitus (T2DM), with particular emphasis on gender-stratified analyses. Methods This cross-sectional investigation analyzed 796 hospitalized T2DM cases. Serum concentrations of TT, DHEAS, and ASD were quantified using chemiluminescence immunoassays. Multivariable logistic regression was utilized to assess the associations between androgen levels and the presence of DR, with analyses conducted separately for men and women to account for sex-specific differences. Results Among male participants, after comprehensive adjustment for potential confounding variables, serum DHEAS levels were independently and inversely linked with DR risk (tertile 3 vs. tertile 1: OR = 0.43, 95% CI: 0.23–0.82; P for trend = 0.007). Restricted cubic spline modeling demonstrated an approximately linear inverse dose-response relationship between DHEAS concentrations and DR risk (overall P < 0.001; nonlinear P = 0.193). No correlations were found between serum TT or ASD levels and DR in men. In female patients, an inverse relationship between TT and DR was attenuated and rendered nonsignificant after full multivariable adjustment, and neither DHEAS nor ASD showed a statistically significant association with DR risk. Conclusions Lower serum DHEAS concentrations are independently linked with elevated DR risk in males with T2DM, suggesting a potential role for DHEAS in the pathophysiology of DR in males.