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.