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

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

Trico, Domenico (författare): University of Pisa

McCollum, Sarah (författare): Yale University

Samuels, Stephanie (författare): Yale University

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Santoro, Nicola (författare): Yale University,University of Molise

Galderisi, Alfonso (författare): Necker-Enfants Malades Hospital

Groop, Leif (författare): Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups

Caprio, Sonia (författare): Yale University

Shabanova, Veronika (författare): Yale University

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(creator_code:org_t)

2022-07-26
2022
Engelska 11 s.
Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992. ; 45:8, s. 1841-1851

Relaterad länk:: http://dx.doi.org/10... (free); visa fler...; https://lup.lub.lu.s...; https://doi.org/10.2...; visa färre...

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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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

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Av författaren/redakt...: Trico, Domenico; McCollum, Sarah; Samuels, Stephan ...; Santoro, Nicola; Galderisi, Alfon ...; Groop, Leif; visa fler...; Caprio, Sonia; Shabanova, Veron ...; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Endokrinologi oc ...

Artiklar i publikationen: Diabetes Care

Av lärosätet: Lunds universitet

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