{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:45:31Z","timestamp":1790628331399,"version":"4.1.0"},"reference-count":47,"publisher":"American Diabetes Association","issue":"8","license":[{"start":{"date-parts":[[2017,7,21]],"date-time":"2017-07-21T00:00:00Z","timestamp":1500595200000},"content-version":"vor","delay-in-days":38,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008796","name":"Allen Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008796","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,8,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>In this study, we aimed to explore the mechanism by which TCF7L2 rs7903146 risk allele confers susceptibility to impaired glucose tolerance (IGT) or type 2 diabetes (T2D) in obese adolescents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>The rs7903146 variant in the TCF7L2 gene was genotyped in a multiethnic cohort of 955 youths. All subjects underwent an oral glucose tolerance test with the use of the Oral Minimal Model to assess insulin secretion, and 33 subjects underwent a hyperinsulinemic-euglycemic clamp. In 307 subjects, a follow-up oral glucose tolerance test was repeated after 3.11 \u00b1 2.36 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The TCF7L2 rs7903146 risk allele was associated with higher 2-h glucose levels in Caucasians (P = 0.006) and African Americans (P = 0.009), and a trend was seen also in Hispanics (P = 0.072). Also, the T allele was associated with decreased \u03b2-cell responsivity and IGT (P &amp;lt; 0.05). Suppression of endogenous hepatic glucose production was lower in subjects with the risk variant (P = 0.006). Finally, the odds of showing IGT\/T2D at follow-up were higher in subjects carrying the minor allele (odds ratio 2.224; 95% CI 1.370\u20133.612; P = 0.0012).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>The rs7903146 variant in the TCF7L2 gene increases the risk of IGT\/T2D in obese adolescents by impairing \u03b2-cell function, and hepatic insulin sensitivity predicts the development of IGT\/T2D over time.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc17-0290","type":"journal-article","created":{"date-parts":[[2017,6,13]],"date-time":"2017-06-13T20:25:25Z","timestamp":1497385525000},"page":"1082-1089","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":77,"title":["The rs7903146 Variant in the\n                    <i>TCF7L2<\/i>\n                    Gene Increases the Risk of Prediabetes\/Type 2 Diabetes in Obese Adolescents by Impairing \u03b2-Cell Function and Hepatic Insulin Sensitivity"],"prefix":"10.2337","volume":"40","clinical-trial-number":[{"clinical-trial-number":"nct01967849","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Catrina","family":"Cropano","sequence":"first","affiliation":[{"name":"1Division of Pediatric Endocrinology, Department of Pediatrics, Yale University School of Medicine, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6437-4173","authenticated-orcid":false,"given":"Nicola","family":"Santoro","sequence":"additional","affiliation":[{"name":"1Division of Pediatric Endocrinology, Department of Pediatrics, Yale University School of Medicine, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif","family":"Groop","sequence":"additional","affiliation":[{"name":"2Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, Malmo, 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