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Fructose can stimulate glucagon-like peptide 1 (GLP-1) secretion in lean adults, in the absence of any anorexic effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We hypothesized that the ingestion of glucose and fructose may differentially stimulate GLP-1 and insulin response in lean adolescents and adolescents with obesity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>We studied 14 lean adolescents [four females; 15.9 \u00b1 1.6 years of age; body mass index (BMI), 21.8 \u00b1 2.2 kg\/m2] and 23 adolescents with obesity (five females; 15.1 \u00b1 1.6 years of age; BMI, 34.5 \u00b1 4.6 kg\/m2). Participants underwent a baseline oral glucose tolerance test to determine their glucose tolerance and estimate insulin sensitivity and \u03b2-cell function [oral disposition index (oDIcpep)]. Eligible subjects received, in a double-blind, crossover design, 75 g of glucose or fructose. Plasma was obtained every 10 minutes for 60 minutes for the measures of glucose, insulin, and GLP-1 (radioimmunoassay) and glucose-dependent insulinotropic polypeptide (GIP; ELISA). Incremental glucose and hormone levels were compared between lean individuals and those with obesity by a linear mixed model. The relationship between GLP-1 increment and oDIcpep was evaluated by regression analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Following the fructose challenge, plasma glucose excursions were similar in both groups, yet the adolescents with obesity exhibited a greater insulin (P &amp;lt; 0.001) and GLP-1 (P &amp;lt; 0.001) increase than did their lean peers. Changes in GIP were similar in both groups. After glucose ingestion, the GLP-1 response (P &amp;lt; 0.001) was higher in the lean group. The GLP-1 increment during 60 minutes from fructose drink was correlated with a lower oDIcpep (r2 = 0.22, P = 0.009).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Fructose, but not glucose, ingestion elicits a higher GLP-1 and insulin response in adolescents with obesity than in lean adolescents. Fructose consumption may contribute to the hyperinsulinemic phenotype of adolescent obesity through a GLP-1\u2013mediated mechanism.<\/jats:p><\/jats:sec>","DOI":"10.1210\/jc.2019-00161","type":"journal-article","created":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T13:52:06Z","timestamp":1554213126000},"page":"3481-3490","source":"Crossref","is-referenced-by-count":32,"title":["Fructose Consumption Contributes to Hyperinsulinemia in Adolescents With Obesity Through a GLP-1\u2013Mediated Mechanism"],"prefix":"10.1210","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8885-3056","authenticated-orcid":false,"given":"Alfonso","family":"Galderisi","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Pediatrics Endocrinology and Diabetes Section, Yale School of Medicine, New Haven, Connecticut"},{"name":"Department of Woman\u2019s and Child\u2019s Health, University of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosimo","family":"Giannini","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pediatrics Endocrinology and Diabetes Section, Yale School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Van Name","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pediatrics Endocrinology and Diabetes Section, Yale School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Caprio","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pediatrics Endocrinology and Diabetes Section, Yale School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2019,4,2]]},"reference":[{"issue":"1","key":"2020071623141182700_bib1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1001\/jama.2013.6562","article-title":"Examining the health effects of fructose","volume":"310","author":"Ludwig","year":"2013","journal-title":"JAMA"},{"issue":"4","key":"2020071623141182700_bib2","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1093\/ajcn\/79.4.537","article-title":"Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity","volume":"79","author":"Bray","year":"2004","journal-title":"Am J Clin Nutr"},{"issue":"7","key":"2020071623141182700_bib3","first-page":"160","article-title":"Dietary fructose consumption among US children and adults: the Third National Health and Nutrition Examination Survey","volume":"10","author":"Vos","year":"2008","journal-title":"Medscape J Med"},{"key":"2020071623141182700_bib4","doi-asserted-by":"crossref","unstructured":"Qi Q , ChuAY, KangJH, JensenMK, CurhanGC, PasqualeLR, RidkerPM, HunterDJ, WillettWC, RimmEB, ChasmanDI, HuFB, QiL. 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