Cross-sectional study of the determinants and associations of sex hormone-binding globulin concentrations in first degree relatives (FDR) of patients with Type 2 Diabetes Mellitus

Aims This study explores the determinants of sex hormone binding globulin (SHBG) and associations with categories of glucose intolerance and undiagnosed diabetes in first-degree relatives (FDR) of patients with Type 2 Diabetes Mellitus (T2D). Methods Anthropometric indices, fasting lipids, glucose, insulin, adiponectin, leptin, SHBG, estradiol (E2), testosterone (TT), androstenedione (AND), dehydroepiandrosterone sulphate (DHEA-S), high-sensitivity C-reactive protein (hs-CRP) and alanine aminotransferase (ALT) were measured in 584 FDR. Homeostasis model assessment-estimate of insulin resistance (HOMA-IR), beta cell function (%B), insulin sensitivity (%S) and free androgen index (FAI) were calculated. Results 266 subjects were normoglycemic; 237 had prediabetes and 81 had undiagnosed diabetes. SHBG decreased stepwise with worsening categories of glucose intolerance in females whereas FAI decreased stepwise with worsening categories in males only. SHBG showed significant positive correlations with adiponectin, and HDL-C and significant negative correlations with body mass index (BMI), waist circumference (WC), Waist:hip ratio (WHR), ALT, triglycerides (TG), %B, leptin and FAI. After adjustment for WHR, only HDL-C and FAI in men and FAI and HbA1c in females remained significantly associated with SHBG. Receiver Operating Characteristic (ROC) curve analysis for detection of diabetes showed that areas under the curve for FAI and SHBG were 0.711 and 0.386 for males and 0.430 and 0.660 for females respectively. Conclusion Associations of SHBG with some anthropometric and metabolic variables in FDR suggests that lower levels is a marker for risk of developing T2D through obesity dependent metabolic pathways but low FAI is a better marker of state of diabetes in males.