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Circulating metabolites are measurable products of metabolic processes that may explain the aetiology of elevated risk. We characterized metabolites associated with prevalent DM and glycaemic measures in South Asians.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included 717 participants from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study, aged 40\u201384\u00a0years. We used baseline fasting serum for metabolomics and demographic, behavioural, glycaemic data from baseline and at 5\u00a0years. We performed LC\u2010MS untargeted\u00a0metabolomic\u00a0and 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 associated with the outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were 258 metabolites with detectable signal in &gt;98% of samples. Thirty\u2010four metabolites were associated with prevalent DM in an elastic net model. Predominant metabolites associated with DM were sphingomyelins, proline (OR 15.86; 95% CI 4.72, 53.31) and betaine (OR 0.03; 0.004, 0.14). Baseline tri\u2010 and di\u2010acylglycerols [DG (18:0\/16:0) (18.36; 11.79, 24.92)] were positively associated with fasting glucose and long\u2010chain acylcarnitines [CAR 26:1 (\u22120.40; \u22120.54, \u22120.27)] were inversely associated with prevalent DM and HbA<jats:sub>1c<\/jats:sub> at follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>A metabolomic signature in South Asians may help determine the unique aetiology of diabetes in this high\u2010risk ethnic group. Future work will externally validate our findings and determine the effects of modifiable risk factors for DM.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.14494","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T07:15:17Z","timestamp":1607411717000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Circulating metabolites and lipids are associated with glycaemic measures in South Asians"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8638-0048","authenticated-orcid":false,"given":"Meghana D.","family":"Gadgil","sequence":"first","affiliation":[{"name":"Division of General Internal Medicine Department of Medicine University of California, San Francisco San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alka M.","family":"Kanaya","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine Department of Medicine University of California, San Francisco San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Sands","sequence":"additional","affiliation":[{"name":"National Phenome Centre Imperial College London Hammersmith Hospital Campus London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Lewis","sequence":"additional","affiliation":[{"name":"National Phenome Centre Imperial College London Hammersmith Hospital Campus London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namratha R.","family":"Kandula","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine and Geriatrics Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Herrington","sequence":"additional","affiliation":[{"name":"Section on 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