{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:05:34Z","timestamp":1790949934778,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T00:00:00Z","timestamp":1589760000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To validate the clusters of Swedish individuals with recent\u2010onset diabetes at differential risk of complications, which were identified in a previous study, in three global populations with long\u2010standing type 2 diabetes (T2D) who were at high cardiovascular risk, and to test for differences in the risk of major diabetes complications and survival endpoints.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>We assigned participants from recent global outcomes trials (DEVOTE [n = 7637], LEADER [n = 9340] and SUSTAIN\u20106 [n = 3297]) to the previously defined clusters according to age at diabetes diagnosis, baseline glycated haemoglobin (HbA1c) and body mass index (BMI). Outcomes were assessed using Kaplan\u2013Meier analysis and log\u2010rank tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The T2D clusters were consistently replicated across the three trial cohorts. The risk of major adverse cardiovascular events and cardiovascular death differed significantly, in all trials, across clusters over a median follow\u2010up duration of 2.0, 3.8 and 2.1\u2009years, respectively, and was highest for the cluster of participants with high HbA1c and low BMI (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;\u20090.05 in DEVOTE and LEADER). In LEADER and SUSTAIN\u20106, the risk of nephropathy differed across clusters (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;\u20090.0001 and\n                      <jats:italic>P<\/jats:italic>\n                      =\u20090.003, respectively). The risk of severe hypoglycaemia differed in DEVOTE (\n                      <jats:italic>P<\/jats:italic>\n                      =\u20090.006).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Previously identified clusters can be replicated in three geographically diverse cohorts of long\u2010standing T2D and are associated with cluster\u2010specific risk profiles for additional clinical and survival outcomes, providing further validation of the clustering methodology. The external validity and stability of clusters across cohorts provides a premise for future work to optimize the clustering approach to yield T2D subgroups with maximum predictive validity who may benefit from subtype\u2010specific treatment paradigms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14063","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T01:58:47Z","timestamp":1587434327000},"page":"1537-1547","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Validation of distinct type 2 diabetes clusters and their association with diabetes complications in the\n                    <scp>DEVOTE<\/scp>\n                    ,\n                    <scp>LEADER<\/scp>\n                    and\n                    <scp>SUSTAIN<\/scp>\n                    \u20106 cardiovascular outcomes trials"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2701-101X","authenticated-orcid":false,"given":"Anna R.","family":"Kahkoska","sequence":"first","affiliation":[{"name":"School of Medicine University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan S.","family":"Geybels","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara R.","family":"Klein","sequence":"additional","affiliation":[{"name":"School of Medicine University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik F.","family":"Kreiner","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus","family":"Marx","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Aachen RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5749-6954","authenticated-orcid":false,"given":"Michael A.","family":"Nauck","sequence":"additional","affiliation":[{"name":"Medical Department I, Diabetes Center Bochum\u2010Hattingen St. Josef\u2010Hospital, Ruhr\u2010University Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Pratley","sequence":"additional","affiliation":[{"name":"AdventHealth Translational Research Institute  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin O.","family":"Wolthers","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9723-3876","authenticated-orcid":false,"given":"John B.","family":"Buse","sequence":"additional","affiliation":[{"name":"School of Medicine University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00618-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(14)70219-0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-018-0728-6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310799"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12859"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/dci18-0007"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(18)30051-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(19)30087-7"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(19)30187-1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615692"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603827"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607141"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-2215"},{"key":"e_1_2_9_15_1","unstructured":"R: A language and environment for statistical computing[computer program]. Vienna Austria: R Foundation for Statistical Computing;2013."},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/dci18-0033"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.14063","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.14063","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.14063","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.14063","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:12:06Z","timestamp":1761869526000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.14063"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,18]]},"references-count":15,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1111\/dom.14063"],"URL":"https:\/\/doi.org\/10.1111\/dom.14063","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,18]]},"assertion":[{"value":"2020-03-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}