Metabolite profiles of incident diabetes and heterogeneity of treatment effect in the diabetes prevention program

the Diabetes Prevention Program Research Group

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2337-2349
Number of pages13
JournalDiabetes
Volume68
Issue number12
DOIs
StatePublished - Dec 1 2019

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Type 2 Diabetes Mellitus
Metformin
Life Style
Therapeutics
Cytosine
Adenosine Monophosphate
Random Allocation
Metabolic Networks and Pathways
Proportional Hazards Models
Phospholipids
Biomarkers
Placebos

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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Metabolite profiles of incident diabetes and heterogeneity of treatment effect in the diabetes prevention program. / the Diabetes Prevention Program Research Group.

In: Diabetes, Vol. 68, No. 12, 01.12.2019, p. 2337-2349.

Research output: Contribution to journalArticle

the Diabetes Prevention Program Research Group. / Metabolite profiles of incident diabetes and heterogeneity of treatment effect in the diabetes prevention program. In: Diabetes. 2019 ; Vol. 68, No. 12. pp. 2337-2349.
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