{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T09:47:27Z","timestamp":1779184047747,"version":"3.51.4"},"reference-count":26,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims and Hypothesis:<\/jats:title>\n                  <jats:p>The insulin secretion\/insulin resistance (IR) (disposition) index (\u0394I\/\u0394G \u00f7 IR, where \u0394 is change from baseline, I is insulin, and G is glucose) is commonly used as a measure of \u03b2-cell function. This relationship is curvilinear and becomes linear when log transformed. \u0394I is determined by 2 variables: insulin secretion rate (ISR) and metabolic clearance of insulin. We postulated that the characteristic curvilinear relationship would be lost if \u0394 plasma C-peptide (\u0394CP) (instead of \u0394 plasma insulin) was plotted against insulin sensitivity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>A total of 441 individuals with impaired glucose tolerance (IGT) from ACT NOW received an oral glucose tolerance test and were randomized to pioglitazone or placebo for 2.4 years.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>Pioglitazone reduced IGT conversion to diabetes by 72% (P &amp;lt; .0001). \u0394I\/\u0394G vs the Matsuda index of insulin sensitivity showed the characteristic curvilinear relationship. However, when \u0394CP\/\u0394G or \u0394ISR\/\u0394G was plotted against the Matsuda index, the curvilinear relationship was completely lost. This discordance was explained by 2 distinct physiologic effects that altered plasma insulin response in opposite directions: 1) increased ISR and 2) augmented metabolic clearance of insulin. The net result was a decline in the plasma insulin response to hyperglycemia during the oral glucose tolerance test. These findings demonstrate a physiologic control mechanism wherein the increase in ISR ensures adequate insulin delivery into the portal circulation to suppress hepatic glucose production while delivering a reduced but sufficient amount of insulin to peripheral tissues to maintain the pioglitazone-mediated improvement in insulin sensitivity without excessive hyperinsulinemia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>These results demonstrate the validity of the disposition index when relating the plasma insulin response to insulin sensitivity but underscore the pitfall of this index when drawing conclusions about \u03b2-cell function, because insulin secretion declined despite an increase in the plasma insulin response.<\/jats:p>\n               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A.G.), San Antonio, Texas 78229"},{"name":"South Texas Veterans Health Care System Audie Murphy Division (R.A.D., D.T.), San Antonio, Texas 78229"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Abdul-Ghani","sequence":"additional","affiliation":[{"name":"Texas Diabetes Institute and University of Texas Health Science Center at San Antonio (R.A.D., D.T., M.A.-G., N.M., A.G.), San Antonio, Texas 78229"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Musi","sequence":"additional","affiliation":[{"name":"Texas Diabetes Institute and University of Texas Health Science Center at San Antonio (R.A.D., D.T., M.A.-G., N.M., A.G.), San Antonio, Texas 78229"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amalia","family":"Gastaldelli","sequence":"additional","affiliation":[{"name":"Texas Diabetes Institute and University of Texas Health Science Center at San Antonio (R.A.D., D.T., M.A.-G., N.M., A.G.), San 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