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Alfred Taubman Medical Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008456","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The global rise in type 2 diabetes is associated with a concomitant increase in diabetic complications. Diabetic polyneuropathy is the most frequent type 2 diabetes complication and is associated with poor outcomes. The metabolic syndrome has emerged as a major risk factor for diabetic polyneuropathy; however, the metabolites associated with the metabolic syndrome that correlate with diabetic polyneuropathy are unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a global metabolomics analysis on plasma samples from a subcohort of participants from the Danish arm of Anglo\u2010Danish\u2010Dutch study of Intensive Treatment of Diabetes in Primary Care (ADDITION\u2010Denmark) with and without diabetic polyneuropathy versus lean control participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to lean controls, type 2 diabetes participants had significantly higher HbA1c (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.0028), BMI (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.0004), and waist circumference (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.0001), but lower total cholesterol (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.0001). Out of 991 total metabolites, we identified 15 plasma metabolites that differed in type 2 diabetes participants by diabetic polyneuropathy status, including metabolites belonging to energy, lipid, and xenobiotic pathways, among others. Additionally, these metabolites correlated with alterations in plasma lipid metabolites in type 2 diabetes participants based on neuropathy status. Further evaluating all plasma lipid metabolites identified a shift in abundance, chain length, and saturation of free fatty acids in type 2 diabetes participants. Importantly, the presence of diabetic polyneuropathy impacted the abundance of plasma complex lipids, including acylcarnitines and sphingolipids.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our explorative study suggests that diabetic polyneuropathy in type 2 diabetes is associated with novel alterations in plasma metabolites related to lipid metabolism.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51367","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T02:19:07Z","timestamp":1620353947000},"page":"1292-1307","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Plasma lipid metabolites associate with diabetic polyneuropathy in a cohort with type 2 diabetes"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0788-3251","authenticated-orcid":false,"given":"Amy 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