Effect of Weight Loss on Atherogenic Risk in Distinct Obesity Phenotypes in Teens

ABSTRACT: Adult literature shows emerging evidence of distinct obesity phenotypes, based on high vs. low levels of insulin resistance (IR), with a difference in prevalence of cardiometabolic risk factors, subclinical and clinical atherosclerotic cardiovascular disease (ASCVD). More intriguing are reports of the differential impact of weight loss, with an improvement in lipid parameters and insulin sensitivity in obese insulin resistant (obese-IR) adults, whereas no change to actual worsening in obese insulin sensitive (obese-IS) adults, despite similar decreases in weight. Pediatric literature reports a direct association between IR, cardiometabolic risk factors and subclinical ASCVD, with an improvement with weight loss. However, there is sparse literature studying the existence of distinct obesity phenotypes in pediatric populations, and, to our knowledge, the differential impact of weight loss on CVD risk factors and subclinical atherosclerosis in obese-IS vs. obese-IR children and adolescents has not been studied. To address these limitations, I propose to conduct a prospective observational study in 100 obese-IR and 100 obese-IS adolescents participating in a nine-month medical weight management program (B'N Fit). I will determine differences in cardiometabolic risk factors and subclinical ASCVD (using carotid intima media thickness) at B'N Fit baseline and the differential impact of weight loss on these factors at 9-months between obese-IR and obese-IS adolescents. In the face of the present epidemic of pediatric obesity, the knowledge gained from this proposed study will be vital for targeting limited clinical resources to those adolescents who most need it and identifying appropriate treatment options for all obese adolescents. Given the current statistic that nearly one in five adolescents is obese, and the likelihood that 80% of these teens will remain obese as adults, investigation into the benefits and potential adverse effects of current medical weight management strategies for obese adolescents will be critical to decreasing the staggering predicted increases in type 2 diabetes, cardiovascular disease, and other obesity- associated chronic diseases over the next decades. My intimate involvement with the B'N Fit program provides me with an excellent venue not only to conduct this research but also to directly translate its findings into clinical practice. The present Career Development Award proposes close ongoing mentorship, formal training in research methods and hands-on training in measures of subclinical ASCVD and adiposity, which will augment my previous training and ensure my emergence as an independent investigator. Given the expertise of highly dedicated mentors, and the continued access to this understudied population, the attached proposal will also provide data to apply for future R01 grants testing specific interventions among different obesity phenotypes and examining the long term effects of weight loss on subclinical atherosclerosis in adolescents.