Baseline phenotypes with preserved β-cell function and high insulin concentrations have the best improvements in glucose tolerance after weight loss: results from the prospective DEXLIFE and EGIR-RISC studies

Sabatini, S., Nolan, J. J., O'Donoghue, G., Kennedy, A., Petrie, J. , Walker, M., O'Gorman, D. J. and Gastaldelli, A. (2024) Baseline phenotypes with preserved β-cell function and high insulin concentrations have the best improvements in glucose tolerance after weight loss: results from the prospective DEXLIFE and EGIR-RISC studies. Metabolism, 155, 155910. (doi: 10.1016/j.metabol.2024.155910) (PMID:38599278)

Abstract

Background: 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.

• Item Type: Articles
• Additional Information: J.J.N., D.O.G., J.P, and M.W., acknowledge the financial support from the European Union's 7Th Framework Programme-Health for the project “Mechanisms of prevention of type 2 diabetes by lifestyle intervention in subjects with pre-diabetes or at high-risk for progression” (DEXLIFE), grant agreement No. 279228. A.G, J.J.N., J.P, and M.W., acknowledge the financial support from the European Union's 5Th Framework Programme-Health for the project “Relationship between Insulin Sensitivity and Cardiovascular risk” (RISC), grant contract No. QLG1-CT-2001-01252. A.G. acknowledges the financial support from the European Union's Horizon 2020 Research and Innovation Programme for the project “Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy” (SOPHIA). SOPHIA has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 875534. This Joint Undertaking received support from the European Union's Horizon 2020 research and innovation program, EFPIA, T1D Exchange, JDRF, and Obesity Action Coalition.
• Keywords: Type 2 diabetes, prediabetes, lifestyle intervention, body weight loss, preventive medicine, machine learning.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Petrie, Professor John

Creator Roles

Petrie, J.: Writing – review and editing, Data curation

• Authors: Sabatini, S., Nolan, J. J., O'Donoghue, G., Kennedy, A., Petrie, J., Walker, M., O'Gorman, D. J., and Gastaldelli, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Metabolism
• Publisher: Elsevier
• ISSN: 0026-0495
• ISSN (Online): 1532-8600
• Published Online: 09 April 2024

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
172261		DEXLIFE: Mechanisms of prevention of type 2 diabetes by lifestyle intervention in subjects with pre-diabetes or at high-risk for progression.	John Petrie	European Commission (EC)	Petrie, Professor John	School of Cardiovascular & Metabolic Health