{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:51:13Z","timestamp":1790614273217,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Hyperglycaemia in type 2 diabetes is caused by varying degrees of two defects: low insulin sensitivity and beta-cell dysfunction. We assessed if subgrouping of patients into three pathophysiological phenotypes according to these defects could identify individuals with high or low risk of future cardiovascular events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>This is a prospective cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We assessed estimates of insulin sensitivity and beta-cell function from the homeostasis model assessment-2 in 4209 individuals with recently diagnosed type 2 diabetes enrolled from general practitioners and outpatient clinics in Denmark. Individuals were followed for a composite cardiovascular endpoint (either atherosclerotic outcomes (myocardial infarction, unstable angina pectoris, stroke, coronary or peripheral revascularization), heart failure, or cardiovascular death) and all-cause mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Totally 417 individuals with the insulinopenic phenotype (high insulin sensitivity and low beta-cell function) had substantially lower risk of cardiovascular events (5-year cumulative incidence: 4.6% vs 10.1%; age-\/sex-adjusted hazard ratio (aHR): 0.49; 95% CI: 0.30\u20130.82) compared with 2685 individuals with the classical phenotype (low insulin sensitivity and low beta-cell function), driven by atherosclerotic events. Conversely, 1107 individuals with the hyperinsulinaemic phenotype (low insulin sensitivity and high beta-cell function) had more cardiovascular events (5-year cumulative incidence: 12.6%; aHR: 1.33; 95% CI: 1.05\u20131.69), primarily driven by increased heart failure and cardiovascular death and increased all-cause mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Simple phenotyping based on insulin sensitivity and beta-cell function predicts distinct future risks of cardiovascular events and death in patients with type 2 diabetes. These results suggest that precision medicine according to underlying type 2 pathophysiology potentially can reduce diabetes complications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/eje-22-0020","type":"journal-article","created":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T09:10:13Z","timestamp":1654593013000},"page":"279-291","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":19,"title":["Risk of cardiovascular events associated with pathophysiological phenotypes of type 2 diabetes"],"prefix":"10.1093","volume":"187","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2711-5927","authenticated-orcid":false,"given":"Jacob Volmer","family":"Stidsen","sequence":"first","affiliation":[{"name":"Steno Diabetes Center Odense, Odense University Hospital , Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2693-5651","authenticated-orcid":false,"given":"Diana Hedevang","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Aarhus University Hospital , Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Erik","family":"Henriksen","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Odense, Odense University Hospital , Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"H\u00f8jlund","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Odense, Odense University Hospital , Odense, Denmark"},{"name":"Department of Clinical Research, University of Southern Denmark , Odense C, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Hecht","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Regional Health Research, University of Southern Denmark , Odense, Denmark"},{"name":"Cardiology Section, Department of Internal Medicine and Steno Diabetes Center Zealand, Holb\u00e6k Hospital , Holb\u00e6k, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reimar Wernick","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Aarhus University Hospital , Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotte Brix","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Aarhus University Hospital , Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens Steen","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Odense, Odense University Hospital , Odense, 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