Recent studies have demonstrated that both insulin resistance (IR) and diabetes were the critical risk factors of heart failure (HF). Importantly, it is reported the high prevalence of previously unknown left ventricular dysfunction including the prevalence of HF preserved EF (HFPEF) in diabetic subjects. However, the underlying mechanism and a biomarker have not been well defined.
To identify underlying mechanism and candidate biomarker of HF in subjects with type 2 diabetes (T2DM), we performed retrospective study of 143 T2DM and 181 non-diabetic subjects. We evaluated cardiac function by echocardiography measuring left ventricular ejection fraction (LVEF), left ventricular mass index (LVMi) and the ratio of early transmitral flow velocity to tissue doppler early diastolic mitral annular velocity (E/e’).
Here we demonstrate that plasma soluble insulin receptor (sIR), a novel biomarker of diabetes, was associated with left ventricular hypertrophy (LVH) and cardiac-dysfunction. Simple regression analysis revealed that circulating sIR was positively correlated with fasting glucose and negatively correlated with fasting insulin. Furthermore, sIR was positively correlated with LVMi and E/e’, and inversely correlated with LVEF (R=0.25; p<0.01, R=0.22, p=0.03, R=-0.19; p=0.02, respectively). Moreover, multivariable regression analysis revealed that sIR was associated with LVMi, E/e’ and LVEF after adjustment for age, gender, BMI, plasma fasting glucose, systolic blood pressure, and eGFR in subjects with T2DM (β= 0.26; p<0.01, β=0.25; p=0.02, β=-0.23; p<0.01,respectively). It is reported that circulating sIR is associated with cleavage of the extracellular domain of insulin receptor and sIR binds to circulating insulin. Thus, our results suggest the possibility that the influence of sIR on insulin signaling may be involved in LVH and cardiac-dysfunction in subjects with T2DM.