{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T02:52:58Z","timestamp":1786675978113,"version":"build-2736575974"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Innovative Medicines Initiative 2 Joint Undertaking","award":["875534"],"award-info":[{"award-number":["875534"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cardiovasc Diabetol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>BMI variability has been associated with increased cardiovascular disease risk in individuals with type 2 diabetes, however comparison between clinical studies and real-world observational evidence has been lacking. Furthermore, it is not known whether BMI variability has an effect independent of HbA1c variability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We investigated the association between BMI variability and 3P-MACE risk in the Harmony Outcomes trial (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099198), and further analysed placebo arms of REWIND (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094440) and EMPA-REG OUTCOME (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092333) trials, followed by real-world data from the Tayside Bioresource (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096980) using Cox regression modelling. BMI variability was determined using average successive variability (ASV), with first major adverse cardiovascular event of non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death (3P-MACE) as the primary outcome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After adjusting for cardiovascular risk factors, a\u2009+\u20091 SD increase in BMI variability was associated with increased 3P-MACE risk in Harmony Outcomes (HR 1.12, 95% CI 1.08\u20131.17,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). The most variable quartile of participants experienced an 87% higher risk of 3P-MACE (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001) relative to the least variable. Similar associations were found in REWIND and Tayside Bioresource. Further analyses in the EMPA-REG OUTCOME trial did not replicate this association. BMI variability\u2019s impact on 3P-MACE risk was independent of HbA1c variability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In individuals with type 2 diabetes, increased BMI variability was found to be an independent risk factor for 3P-MACE across cardiovascular outcome trials and real-world datasets. Future research should attempt to establish a causal relationship between BMI variability and cardiovascular outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12933-024-02299-8","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T16:21:42Z","timestamp":1721146902000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["BMI variability and cardiovascular outcomes within clinical trial and real-world environments in type 2 diabetes: an IMI2 SOPHIA study"],"prefix":"10.1186","volume":"23","author":[{"given":"Robert J.","family":"Massey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Panova-Noeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Mattheus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moneeza K.","family":"Siddiqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanette C.","family":"Schloot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ceriello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewan R.","family":"Pearson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adem Y.","family":"Dawed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"issue":"1","key":"2299_CR1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s12933-022-01445-4","volume":"21","author":"A Ceriello","year":"2022","unstructured":"Ceriello A, Lucisano G, Prattichizzo F, La Grotta R, Franz\u00e9n S, Svensson A-M, et al. 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All study participants have provided informed consent. Tayside Bioresource: The study was approved by the Tayside Regional Ethics Committee and informed consent was obtained from all subjects. REWIND: Ethics review boards gave ethical approval for the analysis of REWIND placebo cohort. EMPA-REG OUTCOME: The EMPA-REG OUTCOME trial was designed and overseen by a steering committee that included academic investigators and employees of Boehringer Ingelheim. The trial was conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines and was approved by local authorities. An independent ethics committee or institutional review board approved the clinical protocol at each participating centre. A full list of participating sites and ethics committees can be found at https:\/\/www.nejm.org\/doi\/suppl\/\n                      \n                      . All the patients provided written informed consent before study entry.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors have reviewed and consent to the publication of this manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Y.C. is employed by Eli Lilly and Company and owns stock. N.C.S. is employed by Lilly Deutschland GmbH and owns stock. A.Y.D. is employed by Novo Nordisk. M.M. and M.P.N. are employed by Boehringer Ingelheim Pharma GmbH & Co.KG.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"256"}}