Obesity is associated with an altered HDL subspecies profle 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

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 insulinresistant (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-fltration chromatography to assess the HDL subspecies profle and compared with that of obese adolescents with T2D (O-T2D). Large HDL subspecies were signifcantly 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 profle 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 profle previously reported in adolescents with T2D, with smaller contributions from insulin resistance and diabetes.

Original languageEnglish
Pages (from-to)1916-1923
Number of pages8
JournalJournal of Lipid Research
Volume58
Issue number9
DOIs
StatePublished - 2017

Bibliographical note

Publisher Copyright:
© 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Funding

This work was supported by National Institutes of Health Grants K23HL118132 (A.S.S.), R01HL67093 (W.S.D.), R01HL104136 (W.S.D.), UL1TR000077 (Cincinnati Children’s), and DK59183 (L.M.D.); The Central Society for Clinical and Translational Research (A.S.S.); and the Cincinnati Pediatric Diabetes and Obesity Center at Cincinnati Children’s Hospital Medical Center (A.S.S.). 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. The authors have no conflicts of interest. Manuscript received 20 June 2017 and in revised form 23 July 2017. Published, JLR Papers in Press, July 25, 2017 DOI https://doi.org/10.1194/jlr.M078667

FundersFunder number
Central Society for Clinical and Translational Research
Cincinnati Pediatric Diabetes and Obesity Center at Cincinnati Children’s Hospital Medical Center
National Institutes of Health (NIH)UL1TR000077, K23HL118132, R01HL67093
National Heart, Lung, and Blood Institute (NHLBI)R21HL104136
Cincinnati Children's Hospital Medical CenterDK59183

    ASJC Scopus subject areas

    • Biochemistry
    • Endocrinology
    • Cell Biology

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