Association between low concentration of serum sex hormone binding globulin and insulin resistance is independent of adiposity, but may be attributable to fasting insulin concentration
Ian Wallace1, Claire McEvoy2, Lesley Hamill2, Jayne Woodside2, Cieran Ennis1,2, Patrick Bell1, Ian Young2, Michelle McKinley2 & Steven Hunter1
Introduction: Recently low circulating levels of sex hormone binding globulin (SHBG) have been shown to be a strong predictor of the risk of developing type 2 diabetes. Genetic studies suggest that this may be a primary causal abnormality and the mechanism may relate to effects on insulin resistance.
Methods: Insulin resistance was assessed using a two-step euglycaemic hyperinsulinaemic clamp (EHC) in 87 (59 male and 28 post-menopausal female) overweight individuals (BMI = 2735 kg/m2) at elevated risk of cardiovascular disease (as assessed by the JBS 2 guidelines). Serum sex hormone binding globulin concentrations were measured using a solid-phase, two-site chemiluminescent immunometric technique. Analysis was performed using Pearsons correlation coefficients and a linear regression model.
Results: For the total group a statistically significant correlation was seen between SHBG and Glucose Infusion Rate (GIR) during step 2 (r=0.384, P<0.001). When analysed by gender this is stronger in females (r=0.628, P<0.001), than in males (r=0.248, P=0.059). Using a linear regression model, including age, gender and percentage body fat a doubling of SHBG was associated with a 26% (95%CI: 5%-51%) increase in GIR (P=0.012) in the total group. Gender was not found to have a statistically significant contribution to this relationship. After inclusion of fasting serum insulin in this model a doubling of SHBG was associated with a 10% (95% CI: -6%29%) increase in GIR (P=0.248).
Conclusions: This is the first large study including both sexes to examine the relationship between insulin resistance and SHBG using the gold-standard EHC. We demonstrate that low serum SHBG concentration is associated with insulin resistance independent of adiposity, with stronger correlation in females. Fasting serum insulin is a significant confounder in this relationship. In spite of this measurement of serum SHBG may be useful in identifying patients with insulin resistance.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: Declaration of Funding: Food Standards Agency, Irish Endocrine Society.