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Obesity and dyslipidemia are known neuropathy risk factors, suggesting lipid profiles early during type 2 diabetes may identify individuals who develop neuropathy later in the disease course. This retrospective cohort study examined lipidomic profiles 10\u2009years prior to type 2 diabetic neuropathy assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Participants comprised members of the Gila River Indian community with type 2 diabetes (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200969) with available stored serum samples and neuropathy assessment 10\u2009years later using the combined Michigan Neuropathy Screening Instrument (MNSI) examination and questionnaire scores. A combined MNSI index was calculated from examination and questionnaire scores. Serum lipids (435 species from 18 classes) were quantified by mass spectrometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The cohort included 17 males and 52 females with a mean age of 45\u2009years (SD\u2009=\u20099\u2009years). Participants were stratified as with (high MNSI index score\u2009&gt;\u20092.5407) versus without neuropathy (low MNSI index score\u2009\u2264\u20092.5407). Significantly decreased medium\u2010chain acylcarnitines and increased total free fatty acids, independent of chain length and saturation, in serum at baseline associated with incident peripheral neuropathy at follow\u2010up, that is, participants had high MNSI index scores, independent of covariates. Participants with neuropathy also had decreased phosphatidylcholines and increased lysophosphatidylcholines at baseline, independent of chain length and saturation. The abundance of other lipid classes did not differ significantly by neuropathy status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Abundance differences in circulating acylcarnitines, free fatty acids, phosphatidylcholines, and lysophosphatidylcholines 10\u2009years prior to neuropathy assessment are associated with neuropathy status in type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.51639","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T01:38:52Z","timestamp":1659577132000},"page":"1392-1404","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Serum lipidomic determinants of human diabetic neuropathy in type 2 diabetes"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3051-3141","authenticated-orcid":false,"given":"Farsad","family":"Afshinnia","sequence":"first","affiliation":[{"name":"Department of Internal Medicine\u2010Nephrology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0138-8436","authenticated-orcid":false,"given":"Evan L.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"NeuroNetwork for Emerging Therapies University of Michigan  Ann Arbor Michigan USA"},{"name":"Department of Neurology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thekkelnaycke M.","family":"Rajendiran","sequence":"additional","affiliation":[{"name":"University of Michigan, Michigan Regional Comprehensive Metabolomics Resource Core  Ann Arbor Michigan USA"},{"name":"Department of Pathology University 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