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The Association of Cardiometabolic, Diet and Lifestyle Parameters With Plasma Glucagon-like Peptide-1: An IMI DIRECT Study

Lookup NU author(s): Dr Ana ViñuelaORCiD, Professor Mark Walker

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.Context: The role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes (T2D) and obesity is not fully understood. Objective: We investigate the association of cardiometabolic, diet, and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D. Methods: We analyzed cross-sectional data from the two Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohorts, cohort 1 (n = 2127) individuals at risk of diabetes; cohort 2 (n = 789) individuals with new-onset T2D. Results: Our multiple regression analysis reveals that fasting total GLP-1 is associated with an insulin-resistant phenotype and observe a strong independent relationship with male sex, increased adiposity, and liver fat, particularly in the prediabetes population. In contrast, we showed that incremental GLP-1 decreases with worsening glycemia, higher adiposity, liver fat, male sex, and reduced insulin sensitivity in the prediabetes cohort. Higher fasting total GLP-1 was associated with a low intake of wholegrain, fruit, and vegetables in people with prediabetes, and with a high intake of red meat and alcohol in people with diabetes. Conclusion: These studies provide novel insights into the association between fasting and incremental GLP-1, metabolic traits of diabetes and obesity, and dietary intake, and raise intriguing questions regarding the relevance of fasting GLP-1 in the pathophysiology T2D.


Publication metadata

Author(s): Eriksen R, White MC, Dawed AY, Perez IG, Posma JM, Haid M, Sharma S, Prehn C, Thomas EL, Koivula RW, Bizzotto R, Mari A, Giordano GN, Pavo I, Schwenk JM, De Masi F, Tsirigos KD, Brunak S, Vinuela A, Mahajan A, McDonald TJ, Kokkola T, Rutters F, Beulens J, Muilwijk M, Blom M, Elders P, Hansen TH, Fernandez-Tajes J, Jones A, Jennison C, Walker M, McCarthy MI, Pedersen O, Ruetten H, Forgie I, Holst JJ, Thomsen HS, Ridderstrale M, Bell JD, Adamski J, Franks PW, Hansen T, Holmes E, Frost G, Pearson ER

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Endocrinology and Metabolism

Year: 2024

Volume: 109

Issue: 9

Pages: e1697-e1707

Print publication date: 01/09/2024

Online publication date: 30/04/2024

Acceptance date: 26/11/2023

Date deposited: 27/08/2024

ISSN (print): 0021-972X

ISSN (electronic): 1945-7197

Publisher: Endocrine Society

URL: https://doi.org/10.1210/clinem/dgae119

DOI: 10.1210/clinem/dgae119

Data Access Statement: The clinical and molecular raw data as well as the processed are available under restricted access due to the informed consent given by study participants, the various national ethical approvals for the present study, and the European General Data Protection Regulation (GDPR); individual-level clinical and molecular data cannot be transferred from the centralized IMI-DIRECT repository. Requests for access will be informed on how data can be accessed via the DIRECT secure analysis platform following submission of an appropriate application. The IMI-DIRECT data access policy is available at https://directdiabetes.org. Supplemental results are available in a repository as detailed in reference (17). 17 Eriksen R, White MC, et al. Data from: The association of cardiometabolic, diet and lifestyle parameters with plasma glucagon-like peptide-1: An IMI DIRECT study. Supplementary material Figshare Deposited 03 October, DOI: 106084/m9figshare24235804. 2023.

PubMed id: 38686701


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Funding

Funder referenceFunder name
115317
EFPIA companies
FP7/2007-2013
European Union's Seventh Framework Programme
Innovative Medicines Initiative Joint Undertaking

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