Obesity is associated with an altered HDL subspecies profile among adolescents with metabolic disease

W Sean Davidson,Anna Heink,Hannah Sexmith,Lawrence M Dolan,Scott M Gordon,James D Otvos,John T Melchior,Deborah A Elder,Jane Khoury,Esmond Geh,Amy S Shah

doi:10.1194/jlr.m078667

Abstract

We aimed to determine the risk factors associated with the depletion of large HDL particles and enrichment of small HDL particles observed in adolescents with T2D. Four groups of adolescents were recruited: 1) lean insulin-sensitive (L-IS), normal BMI and no insulin resistance; 2) lean insulin-resistant (L-IR), normal BMI but insulin resistance (fasting insulin levels ≥ 25 mU/ml and homeostatic model assessment of insulin resistance ≥ 6); 3) obese insulin-sensitive (O-IS), BMI ≥ 95th percentile and no insulin resistance; and 4) obese insulin-resistant (O-IR), BMI ≥ 95th percentile and insulin resistance. Plasma was separated by using gel-filtration chromatography to assess the HDL subspecies profile and compared with that of obese adolescents with T2D (O-T2D). Large HDL subspecies were significantly lower across groups from L-IS > L-IR > O-IS > O-IR > O-T2D (P < 0.0001); small HDL particles were higher from L-IS to O-T2D (P < 0.0001); and medium-sized particles did not differ across groups. The contributions of obesity, insulin resistance, and diabetes to HDL subspecies profile were between 23% and 28%, 1% and 10%, and 4% and 9%, respectively. Obesity is the major risk factor associated with the altered HDL subspecies profile previously reported in adolescents with T2D, with smaller contributions from insulin resistance and diabetes.

Highlights

The Framingham Heart study first established the positive association between HDL-cholesterol (HDL-C) and protection against CVD [1]
BMI, fasting insulin, total cholesterol, and LDL cholesterol (LDL-C) were highest in the obese insulin-resistant (O-IR) group, and HDL-C was lowest
We used gel-filtration chromatography to separate lipoproteins by size among four highly selected participant groups differentiated by their insulin resistance and obesity status

Summary

Introduction

The Framingham Heart study first established the positive association between HDL-cholesterol (HDL-C) and protection against CVD [1]. We found that this HDL subspecies profile is associated with higher pulse wave velocity, a noninvasive measure of atherosclerosis and CVD [15, 16], suggesting that it may confer a higher risk for vascular disease. These findings, taken together with previous clinical reports [17,18,19,20,21,22], indicate that the pattern. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Cincinnati Children’s Hospital Medical Center. Raising HDL-C indiscriminately without considering the type of HDL particles may explain the failure of many of the recent HDL drug trials [5,6,7,8,9]

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Conclusion