Mechanistic Insights Into the Heterogeneity of Glucose Response Classes in Youths With Obesity : A Latent Class Trajectory Approach

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Trico, DomenicoUniversity of Pisa (author)

Mechanistic Insights Into the Heterogeneity of Glucose Response Classes in Youths With Obesity : A Latent Class Trajectory Approach

Article/chapterEnglish2022

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2022-07-26
American Diabetes Association,2022
11 s.

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LIBRIS-ID:oai:lup.lub.lu.se:be9039aa-5b1a-4c5f-bc56-d3b19b4ee36d
https://lup.lub.lu.se/record/be9039aa-5b1a-4c5f-bc56-d3b19b4ee36dURI
https://doi.org/10.2337/dc22-0110DOI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype

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In 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 METHODS Latent 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 b-cell function were estimated by glucose, insulin, and C-peptide modeling. RESULTS Four 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 b-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 b-cell glucose sensitivity. CONCLUSIONS We 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 b-cell glucose sensitivity.

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McCollum, SarahYale University (author)
Samuels, StephanieYale University (author)
Santoro, NicolaUniversity of Molise,Yale University (author)
Galderisi, AlfonsoNecker-Enfants Malades Hospital (author)
Groop, LeifLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups(Swepub:lu)endo-lgr (author)
Caprio, SoniaYale University (author)
Shabanova, VeronikaYale University (author)
University of PisaYale University (creator_code:org_t)

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In:Diabetes Care: American Diabetes Association45:8, s. 1841-18510149-5992

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By the author/editor: Trico, Domenico; McCollum, Sarah; Samuels, Stephan ...; Santoro, Nicola; Galderisi, Alfon ...; Groop, Leif; show more...; Caprio, Sonia; Shabanova, Veron ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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