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

Trico, Domenico ; McCollum, Sarah ; Samuels, Stephanie ; Santoro, Nicola ; Galderisi, Alfonso ; Groop, Leif LU ; Caprio, Sonia and Shabanova, Veronika (2022) In Diabetes Care 45(8). p.1841-1851
Abstract

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.... (More)

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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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes Care
volume
45
issue
8
pages
11 pages
publisher
American Diabetes Association
external identifiers
  • scopus:85135381802
  • pmid:35766976
ISSN
0149-5992
DOI
10.2337/dc22-0110
language
English
LU publication?
yes
id
be9039aa-5b1a-4c5f-bc56-d3b19b4ee36d
date added to LUP
2022-10-07 14:12:51
date last changed
2024-06-13 20:01:28
@article{be9039aa-5b1a-4c5f-bc56-d3b19b4ee36d,
  abstract     = {{<p>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.</p>}},
  author       = {{Trico, Domenico and McCollum, Sarah and Samuels, Stephanie and Santoro, Nicola and Galderisi, Alfonso and Groop, Leif and Caprio, Sonia and Shabanova, Veronika}},
  issn         = {{0149-5992}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1841--1851}},
  publisher    = {{American Diabetes Association}},
  series       = {{Diabetes Care}},
  title        = {{Mechanistic Insights Into the Heterogeneity of Glucose Response Classes in Youths With Obesity : A Latent Class Trajectory Approach}},
  url          = {{http://dx.doi.org/10.2337/dc22-0110}},
  doi          = {{10.2337/dc22-0110}},
  volume       = {{45}},
  year         = {{2022}},
}