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Genetics/Genomes/Proteomics/Metabolomics

Metabolite Profiles of Diabetes Incidence and Intervention Response in the Diabetes Prevention Program

  1. Geoffrey A. Walford1,2,3⇑,
  2. Yong Ma4,5,
  3. Clary Clish6,
  4. Jose C. Florez1,2,3,
  5. Thomas J. Wang7 and
  6. Robert E. Gerszten3,6,8,9
  7. for the Diabetes Prevention Program Research Group*
  1. 1Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA
  2. 2Diabetes Clinical Research Center (Diabetes Unit), Department of Medicine, Massachusetts General Hospital, Boston, MA
  3. 3Harvard Medical School, Boston, MA
  4. 4The George Washington University Biostatistics Center, Rockville, MD
  5. 5Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Washington, DC
  6. 6Metabolomics Platform, Broad Institute, Cambridge, MA
  7. 7Division of Cardiology, Vanderbilt University Medical Center, Nashville, TN
  8. 8Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA
  9. 9Cardiology Division, Massachusetts General Hospital, Boston, MA
  1. Corresponding author: Geoffrey A. Walford, dppmail{at}bsc.gwu.edu.
Diabetes 2016 May; 65(5): 1424-1433. https://doi.org/10.2337/db15-1063
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Abstract

Identifying novel biomarkers of type 2 diabetes risk may improve prediction and prevention among individuals at high risk of the disease and elucidate new biological pathways relevant to diabetes development. We performed plasma metabolite profiling in the Diabetes Prevention Program (DPP), a completed trial that randomized high-risk individuals to lifestyle, metformin, or placebo interventions. Previously reported markers, branched-chain and aromatic amino acids and glutamine/glutamate, were associated with incident diabetes (P < 0.05 for all), but these associations were attenuated upon adjustment for clinical and biochemical measures. By contrast, baseline levels of betaine, also known as glycine betaine (hazard ratio 0.84 per SD log metabolite level, P = 0.02), and three other metabolites were associated with incident diabetes even after adjustment. Moreover, betaine was increased by the lifestyle intervention, which was the most effective approach to preventing diabetes, and increases in betaine at 2 years were also associated with lower diabetes incidence (P = 0.01). Our findings indicate betaine is a marker of diabetes risk among high-risk individuals both at baseline and during preventive interventions and they complement animal models demonstrating a direct role for betaine in modulating metabolic health.

Footnotes

  • Clinical trial reg. no. NCT00004992, clinicaltrials.org.

  • This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db15-1063/-/DC1.

  • * A complete list of members of the Diabetes Prevention Program Research Group is provided in the Supplementary Data.

  • Received July 31, 2015.
  • Accepted January 30, 2016.
  • © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
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Metabolite Profiles of Diabetes Incidence and Intervention Response in the Diabetes Prevention Program
Geoffrey A. Walford, Yong Ma, Clary Clish, Jose C. Florez, Thomas J. Wang, Robert E. Gerszten
Diabetes May 2016, 65 (5) 1424-1433; DOI: 10.2337/db15-1063

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Metabolite Profiles of Diabetes Incidence and Intervention Response in the Diabetes Prevention Program
Geoffrey A. Walford, Yong Ma, Clary Clish, Jose C. Florez, Thomas J. Wang, Robert E. Gerszten
Diabetes May 2016, 65 (5) 1424-1433; DOI: 10.2337/db15-1063
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