Jane Ferguson
Last active: 3/3/2020

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

Chen ZZ, Liu J, Morningstar J, Heckman-Stoddard BM, Lee CG, Dagogo-Jack S, Ferguson JF, Hamman RF, Knowler WC, Mather KJ, Perreault L, Florez JC, Wang TJ, Clish C, Temprosa M, Gerszten RE, Diabetes Prevention Program Research Group
Diabetes. 2019 68 (12): 2337-2349

PMID: 31582408 · PMCID: PMC6868469 · DOI:10.2337/db19-0236

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.

© 2019 by the American Diabetes Association.

MeSH Terms (13)

Adult Aged Biomarkers Cytosine Diabetes Mellitus, Type 2 Female Humans Incidence Life Style Male Metabolome Middle Aged Risk Factors

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