TY - JOUR
T1 - Metabolite profiles of diabetes incidence and intervention response in the diabetes prevention program
AU - Walford, Geoffrey A.
AU - Ma, Yong
AU - Clish, Clary
AU - Florez, Jose C.
AU - Wang, Thomas J.
AU - Gerszten, Robert E.
N1 - Funding Information:
This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants DK081572 (to R.E.G. and T.J.W., co-principal investigators, and J.C.F., co-investigator) and DK099249 (G.A.W.). Additional sources of funding were provided for the DPP study but did not contribute to the metabolite profiling or analyses presented in this article. The NIDDK provided funding to the clinical centers and the coordinating center for the design and conduct of the DPP and the collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service during the DPP. The General Clinical Research Center Program, National Center for Research Resources supported data collection at many of the clinical centers in the DPP. Funding for data collection and participant support in the DPP was also provided by the Office of Minority Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, the Office of Research on Women's Health, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication in the DPP. The research in the DPP 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, Inc., Merck and Co., Nike Sports Marketing, SlimFast 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 provided support services under subcontract with the coordinating center during the DPP. The opinions expressed are those of the investigators and do not necessarily reflect the views of the Indian Health Service or other funding agencies. A complete list of DPP centers, investigators, and staff can be found in the Supplementary Data.
Publisher Copyright:
© 2016 by the American Diabetes Association.
PY - 2016/5
Y1 - 2016/5
N2 - 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 highrisk 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.
AB - 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 highrisk 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.
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U2 - 10.2337/db15-1063
DO - 10.2337/db15-1063
M3 - Article
C2 - 26861782
AN - SCOPUS:84962148165
SN - 0012-1797
VL - 65
SP - 1424
EP - 1433
JO - Diabetes
JF - Diabetes
IS - 5
ER -