{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:39:05Z","timestamp":1790127545745,"version":"4.0.1"},"reference-count":22,"publisher":"American Diabetes Association","issue":"11","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["MOP 133701"],"award-info":[{"award-number":["MOP 133701"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>Alleviation of unrecognized glucotoxicity, with resultant recovery of \u03b2-cell function, could amplify the glucose-lowering effect of pharmacotherapy and contribute to the variable therapeutic response observed among patients with type 2 diabetes (T2D). However, clinical evidence supporting this concept is lacking. Short-term intensive insulin therapy (IIT) can ameliorate glucotoxicity and improve \u03b2-cell function in early T2D. Thus, for evidence of recovery of glucotoxicity-associated \u03b2-cell dysfunction, we sought to determine whether there exists a baseline fasting glucose threshold above which the post-IIT improvement in both \u03b2-cell function and glycemia is amplified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>IIT (glargine, lispro) was administered for 3 weeks to 108 adults with T2D (mean duration 1.8 \u00b1 1.4 years). Oral glucose tolerance tests before and after IIT enabled assessment of \u03b2-cell function by Insulin Secretion-Sensitivity Index-2 and insulinogenic index\/HOMA-insulin resistance. For each level of baseline fasting glycemia from 6.0 to 10.5 mmol\/L, we modeled the difference in IIT-induced percentage change in \u03b2-cell function between those at\/above the indicated glucose level and those below it.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The relationship between baseline fasting glucose and the differential change in \u03b2-cell function was nonlinear. Instead, this relationship was best fit by a cubic regression model with inflection (amplification) at fasting glucose at 9.3 mmol\/L. Moreover, baseline fasting glucose at 9.3 mmol\/L also identified the inflection point at which nonlinear reductions in fasting glucose and 2-h glucose, respectively, were both amplified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>The respective improvements in \u03b2-cell function and glycemia in response to short-term IIT are amplified in those in whom baseline fasting glucose exceeds a defined threshold, consistent with reversal of glucotoxicity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc24-1375","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T12:37:16Z","timestamp":1726835836000},"page":"2017-2023","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":17,"title":["A Glycemic Threshold Above Which the Improvement of \u03b2-Cell Function and Glycemia in Response to Insulin Therapy Is Amplified in Early Type 2 Diabetes: The Reversal of Glucotoxicity"],"prefix":"10.2337","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1989-027X","authenticated-orcid":false,"given":"Ravi","family":"Retnakaran","sequence":"first","affiliation":[{"name":"1Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada"},{"name":"2Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada"},{"name":"3Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajie","family":"Pu","sequence":"additional","affiliation":[{"name":"1Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Ye","sequence":"additional","affiliation":[{"name":"1Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Emery","sequence":"additional","affiliation":[{"name":"1Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stewart B.","family":"Harris","sequence":"additional","affiliation":[{"name":"4Department of Family Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja M.","family":"Reichert","sequence":"additional","affiliation":[{"name":"4Department of Family Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8072-2836","authenticated-orcid":false,"given":"Hertzel 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