{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T16:52:44Z","timestamp":1770483164110,"version":"3.49.0"},"reference-count":14,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":3729,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,7,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>In the Canadian Normoglycemia Outcome Evaluation (CANOE) trial, low-dose rosiglitazone\/metformin reduced the risk of diabetes in subjects with impaired glucose tolerance by 66% over a median of 3.9 years. We evaluate the temporal changes in glycemic control, insulin sensitivity, and \u03b2-cell function during this trial.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>CANOE participants (n = 207) underwent annual oral glucose tolerance testing, enabling temporal comparison of glycemia, insulin sensitivity (Matsuda index), and \u03b2-cell function (insulin secretion-sensitivity index-2 [ISSI-2]) between the rosiglitazone\/metformin and placebo arms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Glycemic parameters and insulin sensitivity improved in the rosiglitazone\/metformin arm in year 1, but deteriorated in the years thereafter as in the placebo arm. Generalized estimating equation analysis confirmed that both insulin sensitivity and \u03b2-cell function decreased over time (Matsuda: \u03b2 = \u22120.0515, P &amp;lt; 0.0001; ISSI-2: \u03b2 = \u22126.6507, P &amp;lt; 0.0001), with no significant time-by-treatment interaction (Matsuda: P = 0.57; ISSI-2: P = 0.22).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Despite preventing incident diabetes, low-dose rosiglitazone\/metformin did not modify the natural history of worsening insulin resistance and \u03b2-cell dysfunction.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc11-0046","type":"journal-article","created":{"date-parts":[[2011,6,28]],"date-time":"2011-06-28T06:32:14Z","timestamp":1309242734000},"page":"1601-1604","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":28,"title":["Changes Over Time in Glycemic Control, Insulin Sensitivity, and \u03b2-Cell Function in Response to Low-Dose Metformin and Thiazolidinedione Combination Therapy in Patients With Impaired Glucose Tolerance"],"prefix":"10.2337","volume":"34","author":[{"given":"Ravi","family":"Retnakaran","sequence":"first","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada"},{"name":"Division of Endocrinology, University of Toronto, Toronto, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Qi","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stewart B.","family":"Harris","sequence":"additional","affiliation":[{"name":"Centre for Studies in Family Medicine, University of Western Ontario, London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony J.","family":"Hanley","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada"},{"name":"Division of Endocrinology, University of Toronto, Toronto, Canada"},{"name":"Department of Nutritional Sciences, University of Toronto, Toronto, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Zinman","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada"},{"name":"Division of Endocrinology, University of Toronto, Toronto, Canada"},{"name":"Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","published-online":{"date-parts":[[2011,6,17]]},"reference":[{"key":"2022031302420277500_B1","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1056\/NEJMoa012512","article-title":"Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin","volume":"346","author":"Knowler","year":"2002","journal-title":"N Engl J Med"},{"key":"2022031302420277500_B2","doi-asserted-by":"crossref","first-page":"537","DOI":"10.2337\/diacare.20.4.537","article-title":"Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study","volume":"20","author":"Pan","year":"1997","journal-title":"Diabetes Care"},{"key":"2022031302420277500_B3","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1056\/NEJM200105033441801","article-title":"Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance","volume":"344","author":"Tuomilehto","year":"2001","journal-title":"N Engl J Med"},{"key":"2022031302420277500_B4","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s00125-005-0097-z","article-title":"The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1)","volume":"49","author":"Ramachandran","year":"2006","journal-title":"Diabetologia"},{"key":"2022031302420277500_B5","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1016\/S0140-6736(02)08905-5","article-title":"Acarbose for prevention of 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CAnadian Normoglycaemia Outcomes Evaluation (CANOE) trial","volume":"8","author":"Zinman","year":"2006","journal-title":"Diabetes Obes Metab"},{"key":"2022031302420277500_B11","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1038\/oby.2008.307","article-title":"Hyperbolic relationship between insulin secretion and sensitivity on oral glucose tolerance test","volume":"16","author":"Retnakaran","year":"2008","journal-title":"Obesity (Silver Spring)"},{"key":"2022031302420277500_B12","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1111\/j.1464-5491.2009.02841.x","article-title":"Evaluation of proposed oral disposition index measures in relation to the actual disposition index","volume":"26","author":"Retnakaran","year":"2009","journal-title":"Diabet Med"},{"key":"2022031302420277500_B13"},{"key":"2022031302420277500_B14","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.2337\/diabetes.54.8.2404","article-title":"Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin","volume":"54","author":"Kitabchi","year":"2005","journal-title":"Diabetes"}],"container-title":["Diabetes 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