4.7 Article

Metabolite Profiles of Incident Diabetes and Heterogeneity of Treatment Effect in the Diabetes Prevention Program

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DIABETES
卷 68, 期 12, 页码 2337-2349

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AMER DIABETES ASSOC
DOI: 10.2337/db19-0236

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资金

  1. National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) of the National Institutes of Health [U01-DKO48489]
  2. National Cancer Institute
  3. National Heart, Lung, and Blood Institute
  4. NIDDK
  5. Indian Health Service
  6. General Clinical Research Center Program, National Center for Research Resources
  7. Department of Veterans Affairs
  8. National Institute of Child Health and Human Development
  9. National Institute on Aging
  10. National Eye Institute
  11. Office of Research on Women's Health
  12. National Institute on Minority Health and Health Disparities
  13. Centers for Disease Control and Prevention
  14. American Diabetes Association
  15. Merck KGaA provides medication for DPPOS
  16. LifeScan, Inc.
  17. Intramural Research Program of the NIDDK
  18. LifeScan, Inc., Health O Meter, Hoechst Marion Roussel, Inc.
  19. Merck-Medco Managed Care
  20. McKesson BioServices Corp.
  21. Matthews Media Group, Inc.
  22. Henry M. Jackson Foundation for the Advancement of Military Medicine

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Novel biomarkers of type 2 diabetes (T2D) and response to preventative treatment in individuals with similar clinical risk may highlight metabolic pathways that are important in disease development. We profiled 331 metabolites in 2,015 baseline plasma samples from the Diabetes Prevention Program (DPP). Cox models were used to determine associations between metabolites and incident T2D, as well as whether associations differed by treatment group (i.e., lifestyle [ILS], metformin [MET], or placebo [PLA]), over an average of 3.2 years of follow-up. We found 69 metabolites associated with incident T2D regardless of treatment randomization. In particular, cytosine was novel and associated with the lowest risk. In an exploratory analysis, 35 baseline metabolite associations with incident T2D differed across the treatment groups. Stratification by baseline levels of several of these metabolites, including specific phospholipids and AMP, modified the effect that ILS or MET had on diabetes development. Our findings highlight novel markers of diabetes risk and preventative treatment effect in individuals who are clinically at high risk and motivate further studies to validate these interactions.

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