@article{f17ad5cd89c04d80a9ac6ce82f81a214,
title = "Metabolite profiles of incident diabetes and heterogeneity of treatment effect in the diabetes prevention program",
abstract = "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.",
author = "{the Diabetes Prevention Program Research Group} and Chen, {Zsu Zsu} and Jinxi Liu and Jordan Morningstar and Heckman-Stoddard, {Brandy M.} and Lee, {Christine G.} and Samuel Dagogo-Jack and Ferguson, {Jane F.} and Hamman, {Richard F.} and Knowler, {William C.} and Mather, {Kieren J.} and Leigh Perreault and Florez, {Jose C.} and Wang, {Thomas J.} and Clary Clish and Marinella Temprosa and Gerszten, {Robert E.}",
note = "Funding Information: Acknowledgments. The DPP Research Group gratefully acknowledges the commitment and dedication of the participants of the DPP and Diabetes Prevention Program Outcomes Study (DPPOS). A complete list of centers, investigators, and staff can be found in Supplementary Data. Funding. Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) of the National Institutes of Health (U01-DKO48489) and supplemental funding by the National Cancer Institute. Further support from the NIDDK included funding to T.J.W. and R.E.G. (R01-DK081572) and training support to Z.-Z.C. (T32-DK007516), who was also supported by the National Heart, Lung, and Blood Institute (T32-HL007374). The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, and Department of Veterans Affairs supported data collection at many of the clinical centers. Funding was also provided by the National Institute of Child Health and Human Development, the National Institute on Aging, the National Eye Institute, the National Heart, Lung, and Blood Institute, the National Cancer Institute, the Office of Research on Women{\textquoteright}s Health, the National Institute on Minority Health and Health Disparities, the Centers for Disease Control and Prevention, and the American Diabetes Association. Merck KGaA provides medication for DPPOS. DPP/DPPOS have also received donated materials from Bristol-Myers Squibb, Parke-Davis, and LifeScan, Inc. This research was also supported, in part, by the Intramural Research Program of the NIDDK. LifeScan, Inc., Health O Meter, Hoechst Marion Roussel, Inc., Merck-Medco Managed Care, Merck & Co., Nike Sports Marketing, Slim Fast Foods Co., and Quaker Oats Co. donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices Corp., Matthews Media Group, Inc., and the Henry M. Jackson Foundation for the Advancement of Military Medicine provided support services under subcontract with the Biostatistics Research and Coordinating Center. Funding Information: The DPP Research Group gratefully acknowledges the commitment and dedication of the participants of the DPP and Diabetes Prevention Program Outcomes Study (DPPOS). A complete list of centers, investigators, and staff can be found in Supplementary Data. Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) of the National Institutes of Health (U01-DKO48489) and supplemental funding by the National Cancer Institute. Further support from the NIDDK included funding to T.J.W. and R.E.G. (R01-DK081572) and training support to Z.-Z.C. (T32- DK007516), who was also supported by the National Heart, Lung, and Blood Institute (T32-HL007374). The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, and Department of Veterans Affairs supported data collection at many of the clinical centers. Funding was also provided by the National Institute of Child Health and Human Development, the National Institute on Aging, the National Eye Institute, the National Heart, Lung, and Blood Institute, the National Cancer Institute, the Office of Research on Women's Health, the National Institute on Minority Health and Health Disparities, the Centers for Disease Control and Prevention, and the American Diabetes Association. Merck KGaA provides medication for DPPOS. DPP/DPPOS have also received donated materials from Bristol-Myers Squibb, Parke-Davis, and LifeScan, Inc. This research was also supported, in part, by the Intramural Research Program of the NIDDK. LifeScan, Inc., Health O Meter, Hoechst Marion Roussel, Inc., Merck-Medco Managed Care, Merck & Co., Nike Sports Marketing, Slim Fast Foods Co., and Quaker Oats Co. donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices Corp., Matthews Media Group, Inc., and the Henry M. Jackson Foundation for the Advancement of Military Medicine provided support services under subcontract with the Biostatistics Research and Coordinating Center. The opinions expressed are those of the investigators and do not necessarily reflect the views of the funding agencies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2019 by the American Diabetes Association.",
year = "2019",
month = dec,
day = "1",
doi = "10.2337/db19-0236",
language = "English (US)",
volume = "68",
pages = "2337--2349",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "12",
}