Abstract 220: Obesity Drives the Decline in Large HDL Subspecies Among Male Adolescents

Abstract

We have shown that adolescents with type 2 diabetes have an altered HDL subspecies profile, characterized by a depletion of large apoE rich HDL particles. We have also shown a significant inverse relationship between this profile and arterial stiffness suggesting that the loss of these particles is associated with early atherosclerosis. We sought to evaluate known risk factors (that contribute to the depletion of large HDL subspecies in adolescents. We evaluated the contributions of obesity, insulin resistance and diabetes to loss of large HDL particles, in five adolescent groups (n=20 per group) with highly specific phenotypes. Insulin resistance was defined by fasting insulin levels and HOMA-IR Adolescent groups were: lean insulin sensitive (normal body mass index (BMI) with no insulin resistance; lean insulin resistant (normal BMI with insulin resistance), obese insulin sensitive (obese BMI with no insulin resistance), obese insulin resistant (obese BMI with insulin resistance), and with type 2 diabetes (obese with insulin resistance and type 2 diabetes by the American Diabetes Association criteria). Stored plasma from each participant was fractionated using gel filtration chromatography to isolate HDL subspecies. The mean age of the cohort was 17.9 ± 1.6 years. Groups did not differ in age and race (50% Caucasian, 50% African American, all male). Large rich HDL subspecies declined significantly across each group from lean insulin sensitive, to lean insulin resistant, to obese insulin sensitive, to obese insulin resistant to type 2 diabetes (p<0.0001). An inverse relationship was also seen for small HDL particles (p<0.0001). Medium size particles did not differ across groups. These data were confirmed by nuclear magnetic resonance spectroscopy. Obesity explained ~50%, insulin resistance ~ 25%, and diabetes ~10% of the decline in large particles between lean insulin sensitive to type 2 diabetes participants. Twenty percent remained unexplained. Obesity appears to drive the decline in large atheroprotective HDL particles in male adolescents. However, contributions of insulin resistance and type 2 diabetes are evident. Whether weight loss reverses this profile and has the potential to improve cardiovascular risk remains to be determined.