Lifestyle and Metformin Treatment Favorably Influence Lipoprotein Subfraction Distribution in the Diabetes Prevention Program (original) (raw)

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1Leonard M. Miller School of Medicine (R.G.), University of Miami, Miami, Florida 33136

*Address all correspondence and requests for reprints to: R. Goldberg, MD, c/o The Diabetes Prevention Program Coordinating Center, Biostatistics Center, George Washington University, 6110 Executive Boulevard, Suite 750, Rockville, Maryland 20852.

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2The Biostatistics Center (M.T.), The George Washington University, Rockville, Maryland 20852

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3LipoScience, Inc (J.O.), Raleigh North Carolina 27616

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4University of Washington School of Medicine (J.B.), Seattle, Washington 98195

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5NW Lipid Research Labs (S.M.), University of Washington, Seattle, Washington 98109

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6Indiana University School of Medicine (K.M.), Indianapolis, Indiana 46202

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7University of Hawaii (R.A.), Honolulu, Hawaii 96813

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8University of California, Los Angeles (K.W.), Alhambra, California 91801

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9Joslin Diabetes Center (E.H.), Boston, Massachusetts 02215

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10University of California, San Diego (E.B.-C.), San Diego, California 92093

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Received:

20 February 2013

Published:

01 October 2013

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R. Goldberg, M. Temprosa, J. Otvos, J. Brunzell, S. Marcovina, K. Mather, R. Arakaki, K. Watson, E. Horton, E. Barrett-Connor, Lifestyle and Metformin Treatment Favorably Influence Lipoprotein Subfraction Distribution in the Diabetes Prevention Program, The Journal of Clinical Endocrinology & Metabolism, Volume 98, Issue 10, 1 October 2013, Pages 3989–3998, https://doi.org/10.1210/jc.2013-1452
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Abstract

Context:

Although intensive lifestyle change (ILS) and metformin reduce diabetes incidence in subjects with impaired glucose tolerance (IGT), their effects on lipoprotein subfractions have not been studied.

Objective:

The objective of the study was to characterize the effects of ILS and metformin vs placebo interventions on lipoprotein subfractions in the Diabetes Prevention Program.

Design:

This was a randomized clinical trial, testing the effects of ILS, metformin, and placebo on diabetes development in subjects with IGT.

Participants:

Selected individuals with IGT randomized in the Diabetes Prevention Program participated in the study.

Interventions:

Interventions included randomization to metformin 850 mg or placebo twice daily or ILS aimed at a 7% weight loss using a low-fat diet with increased physical activity.

Main Outcome Measures:

Lipoprotein subfraction size, density, and concentration measured by magnetic resonance and density gradient ultracentrifugation at baseline and 1 year were measured.

Results:

ILS decreased large and buoyant very low-density lipoprotein, small and dense low-density lipoprotein (LDL), and small high-density lipoprotein (HDL) and raised large HDL. Metformin modestly reduced small and dense LDL and raised small and large HDL. Change in insulin resistance largely accounted for the intervention-associated decreases in large very low-density lipoprotein, whereas changes in body mass index (BMI) and adiponectin were strongly associated with changes in LDL. Baseline and a change in adiponectin were related to change in large HDL, and BMI change associated with small HDL change. The effect of metformin to increase small HDL was independent of adiponectin, BMI, and insulin resistance.

Conclusion:

ILS and metformin treatment have favorable effects on lipoprotein subfractions that are primarily mediated by intervention-related changes in insulin resistance, BMI, and adiponectin. Interventions that slow the development of diabetes may also retard the progression of atherosclerosis.

Copyright © 2013 by The Endocrine Society

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