{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T07:00:24Z","timestamp":1785308424774,"version":"3.55.0"},"reference-count":32,"publisher":"The Endocrine Society","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007052","name":"University of Verona","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glucagon-like peptide-1 (GLP-1) plays a key role in regulating glucose homeostasis and body weight, and GLP-1 receptor agonists have been developed and used for treating both type 2 diabetes and obesity. We hypothesized that genetic variation in the GLP-1 receptor gene (GLP1R) might be associated with the action of GLP-1 itself and, consequently, insulin sensitivity and\/or secretion and circulating GLP-1, in a cohort of children and adolescents with overweight and obesity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a cohort of 1025 Italian children with obesity, 2 GLP1R SNPs (rs6923761 and rs1042044) were analyzed individually and as haplotypes. Associations with fasting (FPG, HbA1c, HOMA-IR) and oral glucose tolerance test (OGTT)-derived metabolic traits (IGI, Matsuda index, oDI, AUCins) were assessed using multivariable linear regression. In 26 children, selected according to their haplotype setting, circulating GLP-1 levels were measured during OGTT at 0, 30, and 120\u2005minutes and analyzed using mixed-effects models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>rs6923761 variant was associated with Matsuda index, IGI, AUCins, and AUCins\/AUCglu ratio (P-all &amp;lt; .031). The haplotype A\u2013C, tagging the rs6923761 variant, was associated with lower FPI, HOMA-IR, IGI, and AUCins (P &amp;lt; .02) as well as higher Matsuda index (P = .009). GLP-1 circulating concentrations varied over time, with lower levels observed at 120\u2005minutes compared with baseline (P &amp;lt; .001). GLP1R haplotype A\u2013C was associated with lower GLP-1 concentrations (P = .025).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GLP1R genetic variants, particularly rs6923761 and the A\u2013C haplotype, are associated with distinct patterns of insulin secretion, insulin sensitivity, and circulating GLP-1 levels in children and adolescents with obesity. These findings provide new insights into the genetic architecture of incretin physiology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag283","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T11:46:53Z","timestamp":1784116013000},"source":"Crossref","is-referenced-by-count":1,"title":["GLP1R haplotypes are associated with insulin secretion and sensitivity in children and adolescents with obesity"],"prefix":"10.1210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4059-4160","authenticated-orcid":false,"given":"Chiara","family":"Zusi","sequence":"first","affiliation":[{"name":"Pediatric Diabetes and Metabolic Disorders Unit, Department of Surgery, Dentistry, Pediatrics and Gynaecology, University of Verona , 37134 Verona ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Caruso","sequence":"additional","affiliation":[{"name":"Department of Mother and Child, Pediatric Unit B, University Hospital of Verona , 37126 Verona ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Gastaldelli","sequence":"additional","affiliation":[{"name":"Pediatric Diabetes and Metabolic Disorders Unit, Department of Surgery, Dentistry, Pediatrics and Gynaecology, University of Verona , 37134 Verona ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Corradi","sequence":"additional","affiliation":[{"name":"Pediatric Diabetes and Metabolic Disorders Unit, Department of Surgery, Dentistry, Pediatrics and Gynaecology, University of Verona , 37134 Verona ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Lobbens","sequence":"additional","affiliation":[{"name":"Pediatric Diabetes and Metabolic Disorders Unit, Department of Surgery, Dentistry, Pediatrics and Gynaecology, University of Verona , 37134 Verona 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