Sex Hormone-Binding Globulin and Cardiac Function in Men with Heart Failure: Possible Role of Diabetes

Background: The association of sex hormone-binding globulin (SHBG) with heart failure (HF) remains a topic of ongoing debate, particularly in the light of type 2 diabetes mellitus (T2DM). We aimed to assess the association of SHBG with clinical and echocardiographic parameters of HF in men according to the presence of T2DM. Methods: Data on baseline characteristics, cardiovascular risk factors and medications, laboratory findings including serum SHBG and total testosterone concentrations, and echocardiographic parameters were prospectively collected for 215 male patients consecutively hospitalized for an acute episode of HF. Results: Patients with T2DM were older (p = 0.013), had a greater body mass index (p = 0.009) and NYHA class (p = 0.001), and were more likely to have hypertension (p < 0.001) or hyperlipidemia (p = 0.032). A moderate correlation among SHBG and total testosterone with the left ventricular ejection fraction (LVEF) was observed only in T2DM patients (r = 0.456) but not among non-T2DM patients (r = 0.194). A multivariate analysis revealed the independent association of increased SHBG levels with lower LVEF values among T2DM patients (ß = -0.542, p < 0.0001), whereas in the same group higher total testosterone was an independent predictor of higher LVEF (ß = 0.531, p < 0.0001) and lower LVDD (ß = -0.442, p = 0.0002) levels. Conclusions: In men with HF and T2DM, in contrast to testosterone, SHBG may have an independent adverse impact on the LVEF, which may account for 12.5% of the variance in LVEF levels. The possible subcellular mechanisms of SHBG in men with diabetic myocardial disorder should be additionally explored.