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 adenosine monophosphate (AMP), modified the effect that ILS or MET had on diabetes development. Our findings highlight novel markers of diabetes risk and preventive treatment effect in individuals that are clinically at high risk and motivate further studies to validate these interactions.
Reference Type
Journal Article
Periodical Full
Diabetes
Publication Year
2019
Publication Date
Oct 3
Publisher
by the American Diabetes Association
Place of Publication
United States
ISSN/ISBN
1939-327X
Accession Number
PMID: 31582408
Document Object Index
b190236 [pii]
PMID
31582408
PMCID
PMC6868469