{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:43:36Z","timestamp":1790009016103,"version":"4.0.1"},"reference-count":29,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T00:00:00Z","timestamp":1558569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To quantify the magnitude and specific contributions of known cardiovascular risk factors leading to higher cardiovascular risk and all\u2010cause mortality caused by type 2 diabetes (T2D).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mediation analysis was performed to assess the relative contributions of known classical risk factors for vascular disease in T2D (insulin resistance, systolic blood pressure, renal function, LDL\u2010cholesterol, triglycerides and micro\u2010albuminuria), and what proportion of the effect of T2D on cardiovascular events and all\u2010cause mortality these factors mediate in the Second Manifestations of ARTerial disease (SMART) cohort consisting of 1910 T2D patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Only 35% (95% CI 15\u201071%) of the excess cardiovascular risk caused by T2D is mediated by the classical cardiovascular risk factors. The largest mediated effect was through insulin resistance [proportion of mediated effect (PME) 18%, 95% CI 3\u201037%], followed by elevated triglycerides (PME 8%, 95% CI 4\u201014%) and micro\u2010albuminuria (PME 7%, 95% CI 3\u201017%). Only 42% (95% CI 18\u201073%) of the excess mortality risk was mediated by the classical risk factors considered. The largest mediated effect was by micro\u2010albuminuria (PME 18%, 95% CI 10\u201029%) followed by insulin resistance (PME 15%, 95% CI 1\u201033%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A substantial amount of the increased cardiovascular risk and all\u2010cause mortality caused by T2D cannot be explained by traditional vascular risk factors. Future research should focus on identifying non\u2010classical pathways that might further explain the increased cardiovascular and mortality risk caused by T2D.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13759","type":"journal-article","created":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T04:05:08Z","timestamp":1557201908000},"page":"1935-1943","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Mediation analysis of the relationship between type 2 diabetes and cardiovascular events and all\u2010cause mortality: Findings from the SMART cohort"],"prefix":"10.1111","volume":"21","author":[{"given":"Shahnam","family":"Sharif","sequence":"first","affiliation":[{"name":"Department of Vascular Medicine University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf H. H.","family":"Groenwold","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"van der Graaf","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gijs F. N.","family":"Berkelmans","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten J.","family":"Cramer","sequence":"additional","affiliation":[{"name":"Department of Cardiology University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3951-5223","authenticated-orcid":false,"given":"Frank L. 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