{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:16:13Z","timestamp":1761894973898,"version":"build-2065373602"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,10,8]],"date-time":"2017-10-08T00:00:00Z","timestamp":1507420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2018,3]]},"abstract":"\n Aims<\/jats:title>\n \n In the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial (\n Clinicaltrials.gov<\/jats:ext-link>\n : NCT000069784), titrated doses of basal insulin glargine targeting fasting normoglycaemia had a neutral effect on cardiovascular outcomes. The dose of insulin required to achieve normoglycaemia provides a unique measurement of each individual's resistance to insulin's action, and was therefore used to examine the link between insulin resistance and cardiovascular outcomes.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n Self\u2010titration of insulin doses targeting a fasting plasma glucose \u22645.3\u2009mmoL\/L (95\u2009mg\/dL) was promoted at every visit and cardiovascular and other serious health outcomes were ascertained. All analyses were restricted to participants allocated to insulin glargine, who added it to lifestyle or 1 glucose\u2010lowering oral agent at randomization. Normoglycaemia was defined as a fasting plasma glucose <5.6\u2009mmol\/L and HbA1c <6% at the 2\u2010year visit. The median of the natural logarithm of insulin doses (expressed per kg of fat\u2010free mass), recorded at every visit from randomization until either the penultimate visit or the first occurrence of a cardiovascular outcome, was analysed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Higher median insulin doses did not reflect incident cardiovascular events overall or in the subset that achieved normoglycaemia. When the dose taken before a cardiovascular event or the penultimate visit was analysed, the adjusted hazard of the composite of cardiovascular death, myocardial infarction or stroke was 0.94 (95% CI 0.88, 1.00) per unit higher dose overall, and 0.91 (95% CI 0.81, 1.01) in the normoglycaemic subset.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Insulin resistance may not promote cardiovascular outcomes in individuals with dysglycaemia.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.13112","type":"journal-article","created":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T05:18:42Z","timestamp":1505193522000},"page":"564-570","source":"Crossref","is-referenced-by-count":9,"title":["Insulin resistance and cardiovascular outcomes in the\n ORIGIN<\/scp>\n trial"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8072-2836","authenticated-orcid":false,"given":"Hertzel C.","family":"Gerstein","sequence":"first","affiliation":[{"name":"Population Health Research Institute Hamilton Health Sciences and McMaster University Hamilton Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1384-1584","authenticated-orcid":false,"given":"Ele","family":"Ferrannini","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council (CNR) Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1169-3036","authenticated-orcid":false,"given":"Matthew C.","family":"Riddle","sequence":"additional","affiliation":[{"name":"Oregon Health and Science University Portland Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salim","family":"Yusuf","sequence":"additional","affiliation":[{"name":"Population Health Research Institute Hamilton Health Sciences and McMaster University Hamilton Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"ORIGIN Trial 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