{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T18:08:13Z","timestamp":1790446093920,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003092","name":"Diabetes Fonds","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003092","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009709","name":"Stichting De Weijerhorst","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009709","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016244","name":"Health Foundation Limburg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016244","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Type 2 diabetes increases the risk of depression, but the mechanisms underlying this association are incompletely understood. We investigated whether microvascular dysfunction, neurodegeneration, low\u2010grade inflammation, advanced glycation end products (AGEs) and arterial stiffness, pathologies that are more common in diabetes, explain, or mediate the association between type 2 diabetes and incident clinically relevant depressive symptoms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We used prospective data from The Maastricht Study, a population\u2010based cohort study. Diabetes status and potential mediators were assessed at baseline. Clinically relevant depressive symptoms (PHQ\u20109 score \u226510) were assessed at baseline and each year during a median of 8.1 (IQR 4.2, 10.1) years of follow\u2010up. Mediation analysis was employed to investigate the mediating effect of microvascular dysfunction (retinal, blood and MRI biomarkers), neurodegeneration (retina and MRI biomarkers), low\u2010grade inflammation (blood biomarkers), AGEs (skin and blood biomarkers) and arterial stiffness (tonometry and ultrasound biomarkers).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Data of 6091 participants (age, 59.4\u2009years [SD 8.6]; 51.3% women; 23.6% type 2 diabetes) were available. Type 2 diabetes was associated with a higher incidence of clinically relevant depressive symptoms (HR:1.37; 95% CI 1.13, 1.65). This association was partly mediated by microvascular dysfunction (proportion mediated:10.4% [95% CI:3.6%, 17.2%]); neurodegeneration (proportion mediated:12.1% [95% CI: 3.9%, 20.3%]); AGEs (proportion mediated:5.4% [95% CI: 3.0%, 8.8%]); and arterial stiffness (proportion mediated:8.4% [95% CI: 3.3%, 13.5%]); but not by low\u2010grade inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The association between type 2 diabetes and a higher risk of clinically relevant depressive symptoms is partly mediated by microvascular dysfunction, neurodegeneration, AGEs and arterial stiffness.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.16527","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T10:54:34Z","timestamp":1750330474000},"page":"4847-4858","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Type 2 diabetes and depression via microvascular dysfunction, neurodegeneration, inflammation, advanced glycation end products (\n                    <scp>AGEs<\/scp>\n                    ), and arterial stiffness"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9025-2011","authenticated-orcid":false,"given":"Indra L. M.","family":"Steens","sequence":"first","affiliation":[{"name":"CARIM Cardiovascular Research Institute Maastricht Maastricht University (UM)  Maastricht The Netherlands"},{"name":"Department of Internal Medicine Maastricht University Medical Center+ (MUMC+)  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda T.","family":"Schram","sequence":"additional","affiliation":[{"name":"CARIM Cardiovascular Research Institute Maastricht Maastricht University (UM)  Maastricht The Netherlands"},{"name":"Department of Internal Medicine Maastricht University Medical Center+ (MUMC+)  Maastricht The Netherlands"},{"name":"Heart and Vascular Center MUMC+  Maastricht The Netherlands"},{"name":"School of Mental Health and Neuroscience MUMC+  Maastricht The Netherlands"},{"name":"Department of Epidemiology Erasmus MC  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfons J. H. M.","family":"Houben","sequence":"additional","affiliation":[{"name":"CARIM Cardiovascular Research Institute Maastricht Maastricht University (UM)  Maastricht The Netherlands"},{"name":"Department of Internal Medicine Maastricht University Medical Center+ (MUMC+)  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tos T. J. M.","family":"Berendschot","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology MUMC+  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacobus F. A.","family":"Jansen","sequence":"additional","affiliation":[{"name":"School of Mental Health and Neuroscience MUMC+  Maastricht The Netherlands"},{"name":"Department of Radiology and Nuclear Medicine Maastricht University Medical Centre+ (MUMC+)  Maastricht The Netherlands"},{"name":"Department of Electrical Engineering Eindhoven University of Technology Eindhoven  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter H.","family":"Backes","sequence":"additional","affiliation":[{"name":"School of Mental Health and Neuroscience MUMC+  Maastricht The Netherlands"},{"name":"Department of Radiology and Nuclear Medicine Maastricht University Medical Centre+ (MUMC+)  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie","family":"Koster","sequence":"additional","affiliation":[{"name":"CAPHRI Care and Public Health Research Institute  Maastricht UM The Netherlands"},{"name":"Department of Social Medicine Maastricht University (UM)  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Bosma","sequence":"additional","affiliation":[{"name":"CAPHRI Care and Public Health Research Institute  Maastricht UM The Netherlands"},{"name":"Department of Social Medicine Maastricht University (UM)  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone J. 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