UCSF

Introduction & Objective: Lifestyle interventions are effective type 2 diabetes (T2D) prevention strategies, yet little is known about metabolic pathways associated with intervention response in at-risk individuals. The study's purpose was to characterize the baseline metabolome in adults at risk for T2D who responded to a 12-month lifestyle intervention randomized controlled trial with significantly reduced fasting blood glucose (FBG). Methods: This study analyzed de novo untargeted primary metabolome data from 113 plasma samples stored in a biorepository. The parent study recruited participants from San Diego and San Francisco communities between 2009-2012. Data were acquired via the West Coast Metabolomics Core Laboratory using validated liquid chromatography mass spectrometry methods and 15-25 internal standards. Metabolites were quantified by peak heights. Relative concentrations were compared between lifestyle intervention responders and non-responders using independent t-tests and then adjusted for multiple comparisons. Results: Six metabolites were significantly different (unadj p<0.05) between the group of responders and non-responders (pelargonic acid, oleic acid, lysine, hypoxanthine, heptanoic acid, 3-hydroxybutyric acid). Conclusions: At-risk adults in our sample who responded to a lifestyle intervention with significantly decreased FBG exhibited baseline differences in primary metabolism compared with those that did not respond. Findings align with our previously work in this sample characterizing the gene targets and microRNAs, which implicated novel pathways of neurodegenerative and protein misfolding disorders, as well as immune function and inflammation pathways known to be associated with T2D. Findings may help to refine target biological pathways for prevention therapies or define a subtype of participants who are best suited for lifestyle interventions to manage T2D risk. Disclosure: K.A. Lewis: None. B.M. Stroebel: None. L. Zhang: None. A.M. Kanaya: None. E. Flowers: None. Funding: Larry L. Hillblom Foundation (2022-D-011-FEL)