دورية أكاديمية
Mechanistic Insights Into the Heterogeneity of Glucose Response Classes in Youths With Obesity: A Latent Class Trajectory Approach
| العنوان: | Mechanistic Insights Into the Heterogeneity of Glucose Response Classes in Youths With Obesity: A Latent Class Trajectory Approach |
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| المؤلفون: | Tricò, Domenico, McCollum, Sarah, Samuels, Stephanie, Santoro, Nicola, Galderisi, Alfonso, Groop, Leif, Caprio, Sonia, Shabanova, Veronika |
| المساهمون: | Tricò, Domenico, Mccollum, Sarah, Samuels, Stephanie, Santoro, Nicola, Galderisi, Alfonso, Groop, Leif, Caprio, Sonia, Shabanova, Veronika |
| سنة النشر: | 2022 |
| المجموعة: | ARPI - Archivio della Ricerca dell'Università di Pisa |
| مصطلحات موضوعية: | Adolescent, Blood Glucose, Glucose, Human, Insulin, Obesity, Glucose Intolerance, Insulin Resistance |
| الوصف: | OBJECTIVEIn a large, multiethnic cohort of youths with obesity, we analyzed pathophysiological and genetic mechanisms underlying variations in plasma glucose responses to a 180 min oral glucose tolerance test (OGTT).RESEARCH DESIGN AND METHODSLatent class trajectory analysis was used to identify various glucose response profiles to a nine-point OGTT in 2,378 participants in the Yale Pathogenesis of Youth-Onset T2D study, of whom 1,190 had available TCF7L2 genotyping and 358 had multiple OGTTs over a 5 year follow-up. Insulin sensitivity, clearance, and beta-cell function were estimated by glucose, insulin, and C-peptide modeling.RESULTSFour latent classes (1 to 4) were identified based on increasing areas under the curve for glucose. Participants in class 3 and 4 had the worst metabolic and genetic risk profiles, featuring impaired insulin sensitivity, clearance, and beta-cell function. Model-predicted probability to be classified as class 1 and 4 increased across ages, while insulin sensitivity and clearance showed transient reductions and b-cell function progressively declined. Insulin sensitivity was the strongest determinant of class assignment at enrollment and of the longitudinal change from class 1 and 2 to higher classes. Transitions between classes 3 and 4 were explained only by changes in beta-cell glucose sensitivity.CONCLUSIONSWe identified four glucose response classes in youths with obesity with different genetic risk profiles and progressive impairment in insulin kinetics and action. Insulin sensitivity was the main determinant in the transition between lower and higher glucose classes across ages. In contrast, transitions between the two worst glucose classes were driven only by beta-cell glucose sensitivity. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35766976; info:eu-repo/semantics/altIdentifier/wos/WOS:000843954800021; volume:45; issue:8; firstpage:1841; lastpage:1851; numberofpages:11; journal:DIABETES CARE; http://hdl.handle.net/11568/1155345Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85135381802 |
| DOI: | 10.2337/dc22-0110 |
| الإتاحة: | https://doi.org/10.2337/dc22-0110Test http://hdl.handle.net/11568/1155345Test |
| رقم الانضمام: | edsbas.1D7415BD |
| قاعدة البيانات: | BASE |
| DOI: | 10.2337/dc22-0110 |
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