{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T17:03:51Z","timestamp":1768583031857,"version":"3.49.0"},"reference-count":34,"publisher":"American Physiological Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"<jats:p> Short-term intensive insulin therapy (IIT) can improve pancreatic \u03b2-cell function when administered early in the course of type 2 diabetes mellitus (T2DM). However, the degree of improvement in response to this therapy varies between patients. Thus, we sought to characterize the determinants of improvement in \u03b2-cell function in response to short-term IIT in early T2DM. Sixty-three patients with mean 3.0 \u00b1 2.1 yr duration of T2DM and Hb A<jats:sub>1c<\/jats:sub> of 6.8 \u00b1 0.8% underwent 4 wk of IIT consisting of basal insulin detemir and premeal insulin aspart, with oral glucose tolerance test administered at baseline and 1 day post-IIT. \u03b2-Cell function before and after IIT was assessed by Insulin Secretion Sensitivity Index-2 (ISSI-2). Reversibility of \u03b2-cell dysfunction was defined as percentage change in ISSI-2 of \u226525%. Overall, the study population experienced an increase in ISSI-2 from baseline to post-IIT ( P = 0.01), with one-third of participants achieving \u226525% improvement in ISSI-2. Compared with their peers, those with increases in ISSI-2 of \u226525% had greater decrements in fasting glucose ( P &lt; 0.0001), Hb A<jats:sub>1c<\/jats:sub> ( P = 0.001), ALT ( P = 0.04), AST ( P = 0.02), and HOMA-IR ( P &lt; 0.0001). On logistical regression analysis, baseline Hb A<jats:sub>1c<\/jats:sub> (OR = 2.83, 95% CI 1.16\u20136.88, P = 0.02) and change in HOMA-IR (OR = 0.008, 95%CI 0.0004\u20130.16, P = 0.001) emerged as independent predictors of reversibility of \u03b2-cell dysfunction. Indeed, reversibility of \u03b2-cell dysfunction was achieved in only those participants in whom IIT yielded an improvement in HOMA-IR. In conclusion, decline in HOMA-IR may be a key determinant of improvement of \u03b2-cell function in response to short-term IIT, suggesting a fundamental contribution of insulin resistance to the reversible component of \u03b2-cell dysfunction in early T2DM. <\/jats:p>","DOI":"10.1152\/ajpendo.00447.2013","type":"journal-article","created":{"date-parts":[[2013,10,16]],"date-time":"2013-10-16T00:46:04Z","timestamp":1381884364000},"page":"E1398-E1407","source":"Crossref","is-referenced-by-count":54,"title":["Determinants of reversibility of \u03b2-cell dysfunction in response to short-term intensive insulin therapy in patients with early type 2 diabetes"],"prefix":"10.1152","volume":"305","author":[{"given":"Caroline Kaercher","family":"Kramer","sequence":"first","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada,"},{"name":"Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haysook","family":"Choi","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Zinman","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada,"},{"name":"Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada; 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