Impaired left ventricular diastolic function in overweight youth is associated with insulin resistance, subclinical inflammation and adipokine dysregulation: a novel cardiometabolic link

Abstract

Impaired left ventricular diastolic function is the first sign of obesity cardiomyopathy and is evident in obese children (1) and adolescents (2). Whether this occurs due to adiposity, obesity-induced inflammation and/or insulin resistance (IR) is unclear.Objective To evaluate if overweight and obese youth have adverse cardiovascular structure a function compared with non-overweight youth and to determine whether these changes are associated with IR and adipokine dysregulation.Methods 35 overweight and obese (15.1p1.6 y; M:F, 14:21; BMI SDS 2.0p0.8) and 30 non-overweight youth (14.9p2.3 y; M:F, 19:11; BMI SDS -0.1p0.9) participated in the study. Height (Ht), weight, waist circumference (WC) were measured with resting blood pressure. Body mass index (BMI), BMI SDS and WC/Ht were calculated as markers of adiposity. Fasting blood samples were analysed for glucose, insulin, lipid profile, hs-CRP, interleukin (IL)-1b, IL-6, IL-1 receptor antagonist (RA), TNF-a, leptin, adiponectin and resistin. A homeostatic model of assessment (HOMA-IR) was calculated for IR. Echocardiography was used to determine left atrial (LA) and left ventricular (LV) volume, LA area and LV mass. Using transthoracic Doppler echocardiography, diastolic LV function was assessed by recording EA ratio (ratio of early and late diastolic LV filling), septal E prime (LV myocardial elasticity) and E/er (LV filling pressures). Results Overweight and obese youth compared to non-overweight controls had higher fasting insulin, hs-CRP, triglycerides and cholesterol (all pl0.001), LDL (p=0.001) and lower HDL (pl0.05). Compared to non-overweight (NO) and non-insulin resistant (NIR) overweight youth (n=19), IR overweight youth (IR defined as HOMA-IRg3.0; n=16) had higher hs-CRP, resistin (both pl0.01), IL-6 (pl0.05), IL-1RA and leptin (both pl0.001) and lower adiponectin (pl0.001). Diastolic function was impaired in IR overweight youth compared with NO youth, as indicated by a lower EA ratio and septal E prime (pl0.05, pl0.001 respectively) and higher E/er (pl0.001). Septal E prime and E/er were strongly correlated with BMI SDS and WC/Ht (all pl0.001). In addition, septal E prime was significantly associated with insulin, adiponectin (both p=0.005), hs-CRP, leptin and resistin (all pl0.05) independently of blood pressure in a Spearmanrs correlation analysis.Conclusion Diastolic function of the left ventricle was impaired in overweight and obese youth compared with non-overweight controls, particularly in those with IR. These changes were correlated with measures of adiposity and adipokines. Thus, overweight youth with IR and adipokine dysregulation are more likely to have impaired left ventricular diastolic function which may predispose to premature cardiovascular disease in adulthood.