{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T12:03:26Z","timestamp":1778155406528,"version":"3.51.4"},"reference-count":45,"publisher":"American Diabetes Association","issue":"9","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,9,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>To determine whether \u03b2-cell hyperresponsiveness and insulin resistance in youth versus adults in the Restoring Insulin Secretion (RISE) Study are related to increased glucagon release.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>In 66 youth and 350 adults with impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes (drug naive), we performed hyperglycemic clamps and oral glucose tolerance tests (OGTTs). From clamps we quantified insulin sensitivity (M\/I), plasma fasting glucagon and C-peptide, steady-state glucagon and C-peptide at glucose of 11.1 mmol\/L, and arginine-stimulated glucagon (acute glucagon response [AGR]) and C-peptide (ACPRmax) responses at glucose &amp;gt;25 mmol\/L.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Mean \u00b1 SD fasting glucagon (7.63 \u00b1 3.47 vs. 8.55 \u00b1 4.47 pmol\/L; P = 0.063) and steady-state glucagon (2.24 \u00b1 1.46 vs. 2.49 \u00b1 1.96 pmol\/L, P = 0.234) were not different in youth and adults, respectively, while AGR was lower in youth (14.1 \u00b1 5.2 vs. 16.8 \u00b1 8.8 pmol\/L, P = 0.001). Significant age-group differences in insulin sensitivity, fasting C-peptide, steady-state C-peptide, and ACPRmax were not related to glucagon. Fasting glucose and glucagon were positively correlated in adults (r = 0.133, P = 0.012) and negatively correlated in youth (r = \u22120.143, P = 0.251). In both age-groups, higher fasting glucagon was associated with higher fasting C-peptide (youth r = 0.209, P = 0.091; adults r = 0.335, P &amp;lt; 0.001) and lower insulin sensitivity (youth r = \u22120.228, P = 0.066; adults r = \u22120.324, P &amp;lt; 0.001). With comparable fasting glucagon, youth had greater C-peptide and lower insulin sensitivity. OGTT suppression of glucagon was greater in youth.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Youth with IGT or recently diagnosed type 2 diabetes (drug naive) have hyperresponsive \u03b2-cells and lower insulin sensitivity, but their glucagon concentrations are not increased compared with those in adults. Thus, \u03b1-cell dysfunction does not appear to explain the difference in \u03b2-cell function and insulin sensitivity in youth versus adults.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc21-0460","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T20:30:24Z","timestamp":1623789024000},"page":"1961-1969","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":19,"title":["Hyperglucagonemia Does Not Explain the \u03b2-Cell Hyperresponsiveness and Insulin Resistance in Dysglycemic Youth Compared With Adults: Lessons From the RISE Study"],"prefix":"10.2337","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct01779362","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01779375","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01763346","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7307-9002","authenticated-orcid":false,"given":"Steven E.","family":"Kahn","sequence":"first","affiliation":[{"name":"VA Puget Sound Health Care System, Seattle, WA"},{"name":"University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8696-7500","authenticated-orcid":false,"given":"Kieren J.","family":"Mather","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine, Indianapolis, 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