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Lookup NU author(s): Professor Mark Walker
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2024 The AuthorsBackground: Weight loss and lifestyle intervention improve glucose tolerance delaying the onset of type 2 diabetes (T2D), but individual responses are highly variable. Determining the predictive factors linked to the beneficial effects of weight loss on glucose tolerance could provide tools for individualized prevention plans. Thus, the aim was to investigate the relationship between pre-intervention values of insulin sensitivity and secretion and the improvement in glucose metabolism after weight loss. Methods: In the DEXLIFE cohort (373 individuals at high risk of T2D, assigned 3:1 to a 12-week lifestyle intervention or a control arm, Trial Registration: ISRCTN66987085), K-means clustering and logistic regression analysis were performed based on pre-intervention indices of insulin sensitivity, insulin secretion (AUC-I), and glucose-stimulated insulin response (ratio of incremental areas of insulin and glucose, iAUC I/G). The response to the intervention was evaluated in terms of reduction of OGTT-glucose concentration. Clusters' validation was done in the prospective EGIR-RISC cohort (n = 1538). Results: Four replicable clusters with different glycemic and metabolomic profiles were identified. Individuals had similar weight loss, but improvement in glycemic profile and β-cell function was different among clusters, highly depending on pre-intervention insulin response to OGTT. Pre-intervention high insulin response was associated with the best improvement in AUC-G, while clusters with low AUC-I and iAUC I/G showed no beneficial effect of weight loss on glucose control, as also confirmed by the logistic regression model. Conclusions: Individuals with preserved β-cell function and high insulin concentrations at baseline have the best improvement in glucose tolerance after weight loss.
Author(s): Sabatini S, Nolan JJ, O'Donoghue G, Kennedy A, Petrie J, Walker M, O'Gorman DJ, Gastaldelli A
Publication type: Article
Publication status: Published
Journal: Metabolism: Clinical and Experimental
Year: 2024
Volume: 155
Print publication date: 01/06/2024
Online publication date: 08/04/2024
Acceptance date: 04/04/2024
Date deposited: 14/05/2024
ISSN (print): 0026-0495
ISSN (electronic): 1532-8600
Publisher: W.B. Saunders
URL: https://doi.org/10.1016/j.metabol.2024.155910
DOI: 10.1016/j.metabol.2024.155910
PubMed id: 38599278
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