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 high-risk 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.
Reference Type
Journal Article
Periodical Full
Diabetes
Publication Year
2016
Publication Date
May
Volume
65
Issue
5
Start Page
1424
Other Pages
1433
Publisher
American Diabetes Association
Place of Publication
United States
ISSN/ISBN
0012-1797
Document Object Index
10.2337/db15-1063
URL
https://www.ncbi.nlm.nih.gov/pubmed/26861782
PMID
26861782
PMCID
PMC4839205