UCSF

South Asians are at higher risk for diabetes (DM) than many other racial/ethnic groups. Circulating metabolites are measurable products of metabolic processes that may explain the etiology of elevated risk. We characterized metabolites associated with prevalent DM and incident glycemic measures in South Asians. We included 717 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study, aged 40-84 years. We used baseline fasting serum for metabolomics and demographic, behavioral, glycemic data from baseline and at 5 years. We performed LC-MS untargeted metabolomic and lipidomic analysis with targeted integration of known signals. Individual linear and ordinal logistic regression models were adjusted for age, sex, BMI, diet, exercise, alcohol, smoking and family history of DM followed by elastic net regression to identify metabolites most contributory to the outcome. There were 258 metabolites with detectable signal in >98% of samples. Fifty-nine metabolites were associated with prevalent DM, 32 with fasting glucose and 45 with HbA1c at follow-up [FDR < 0.05]. An elastic net model identified a subset of important metabolites (Table 1). Predominant metabolites associated with glycemic measures in South Asians were sphingomyelins, tri- and di-acylglycerols and carnitines. Future work will externally validate our findings and determine the effects of modifiable risk factors for DM. Disclosure: M.D. Gadgil: None. C. Sands: None. M.R. Lewis: None. A.M. Kanaya: None. N.R. Kandula: None. D.M. Herrington: None. Funding: National Institutes of Health (1K23DK119404-01A1)