{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:49:56Z","timestamp":1792788596922,"version":"4.5.0"},"reference-count":51,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["321428"],"award-info":[{"award-number":["321428"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Heath"},{"DOI":"10.13039\/501100006306","name":"Sigrid Juselius Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005633","name":"Finnish Foundation for Cardiovascular Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004092","name":"Kuopio University Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004092","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centre of Excellence of Cardiovascular and Metabolic Diseases"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Diabetic retinopathy (DR) is a specific microvascular complication in patients with diabetes and the leading cause of blindness. Recent advances in omics, especially metabolomics, offer the possibility identifying novel potential biomarkers for DR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim was to identify metabolites associated with DR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a 12-year follow-up study including 1349 participants with type 2 diabetes (1021 without DR, 328 with DR) selected from the METSIM cohort. Individuals who had retinopathy before the baseline study were excluded (n = 63). The diagnosis of retinopathy was based on fundus photography examination. We performed nontargeted metabolomics profiling to identify metabolites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found 17 metabolites significantly associated with incident DR after adjustment for confounding factors. Among amino acids, N-lactoyl isoleucine, N-lactoyl valine, N-lactoyl tyrosine, N-lactoyl phenylalanine, N-(2-furoyl) glycine, and 5-hydroxylysine were associated with an increased risk of DR, and citrulline with a decreased risk of DR. Among the fatty acids N,N,N-trimethyl-5-aminovalerate was associated with an increased risk of DR, and myristoleate (14:1n5), palmitoleate (16:1n7), and 5-dodecenoate (12:1n7) with a decreased risk of DR. Sphingomyelin (d18:2\/24:2), a sphingolipid, was significantly associated with a decreased risk of DR. Carboxylic acid maleate and organic compounds 3-hydroxypyridine sulfate, 4-vinylphenol sulfate, 4-ethylcatechol sulfate, and dimethyl sulfone were significantly associated with an increased risk of DR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study is the first large population-based longitudinal study to identify metabolites for DR. We found multiple metabolites associated with an increased and decreased risk for DR from several different metabolic pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgad452","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T08:19:10Z","timestamp":1691569150000},"page":"100-106","source":"Crossref","is-referenced-by-count":45,"title":["Metabolites as Risk Factors for Diabetic Retinopathy in Patients With Type 2 Diabetes: A 12-Year Follow-up Study"],"prefix":"10.1210","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0225-842X","authenticated-orcid":false,"given":"Lilian","family":"Fernandes Silva","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland , 70211 Kuopio , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Hokkanen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland , 70211 Kuopio , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6657-2659","authenticated-orcid":false,"given":"Jagadish","family":"Vangipurapu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland , 70211 Kuopio , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anniina","family":"Oravilahti","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland , 70211 Kuopio , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3394-7749","authenticated-orcid":false,"given":"Markku","family":"Laakso","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland , 70211 Kuopio , Finland"},{"name":"Department of Internal Medicine, Kuopio University Hospital , 70211 Kuopio , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2023,8,10]]},"reference":[{"issue":"9735","key":"2023122122201658900_dgad452-B1","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/S0140-6736(09)62124-3","article-title":"Diabetic retinopathy","volume":"376","author":"Cheung","year":"2010","journal-title":"Lancet"},{"issue":"1","key":"2023122122201658900_dgad452-B2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0161-6420(95)31052-4","article-title":"The Wisconsin epidemiologic study of diabetic retinopathy. 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