Impaired Left Ventricular Diastolic Function in Overweight Youth is Associated with Insulin Resistance, Subclinical Inflammation and Adipokine Dysregulation A Novel Cardiometabolic Link

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 677-696-Obesity Physiology & Epidemiology
Clinical
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-693
Rachana Dahiya1, Sarah P. Shultz2, Kristen Gibbons3, Danusia Duncan4, John Cardinal5, Karam Kostner4, Nuala Byrne6, Andrew P. Hills7, Mark Harris8, Louise S. Conwell9 and Gary Martin Leong*10
1Mater Children's Hospital, South Brisbane, Australia, 2Massey University, Wellington, New Zealand, 3Mater Medical Research Institute, South Brisbane, Australia, 4Mater Adults Hospital, South Brisbane, Australia, 5Pathology Queensland, Herston, Australia, 6Institute of Health and Biomedic, Brisbane, QLD, Australia, 7Mater Medical Research Institute, South Brisbane, Australia, 8Mater Children's Hosp, South Brisbane QLD, Australia, 9Royal Children's Hospital, Brisbane, Australia, 10The University of Queensland, St Lucia QLD, Australia
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 & function compared with non-overweight youth and to determine whether these changes are associated with IR and adipokine dysregulation.

Methods

35 overweight and obese (15.1±1.6 y; M:F, 14:21; BMI SDS 2.0±0.8) and 30 non-overweight youth (14.9±2.3 y; M:F, 19:11; BMI SDS -0.1±0.9) 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/e’ (LV filling pressures).  

Results

Overweight and obese youth compared to non-overweight controls had higher fasting insulin, hs-CRP, triglycerides and cholesterol (all p<0.001), LDL (p=0.001) and lower HDL (p<0.05). Compared to non-overweight (NO) and non-insulin resistant (NIR) overweight youth (n=19), IR overweight youth (IR defined as HOMA-IR>3.0; n=16) had higher hs-CRP, resistin (both p<0.01), IL-6 (p<0.05), IL-1RA and leptin (both p<0.001) and lower adiponectin (p<0.001). Diastolic function was impaired in IR overweight youth compared with NO youth, as indicated by a lower EA ratio and septal E prime (p<0.05, p<0.001 respectively) and higher E/e’ (p<0.001). Septal E prime and E/e’ were strongly correlated with BMI SDS and WC/Ht (all p<0.001). In addition, septal E prime was significantly associated with insulin, adiponectin (both p=0.005), hs-CRP, leptin and resistin (all p<0.05) independently of blood pressure in a Spearman’s 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.

(1) Harada K et al., Pediatr Cardiol 2001;22:273-8. (2) Shah AS et al., Diabetologia 2011;54:722-30.

Nothing to Disclose: RD, SPS, KG, DD, JC, KK, NB, APH, MH, LSC, GML

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Golden Casket Mater Children’s Hospital Research Fund; Australian Technology Network Centre for Metabolic Fitness