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

Rebeca Eriksen, Margaret C. White, Adem Y. Dawed, Isabel Garcia Perez, Joram M. Posma, Mark Haid, Sapna Sharma, Cornelia Prehn, E. Louise Thomas, Robert W. Koivula, Roberto Bizzotto, Andrea Mari, Giuseppe N. Giordano, Imre Pavo, Jochen M. Schwenk, Federico De Masi, Konstantinos D. Tsirigos, Søren Brunak, Ana Viñuela, Anubha MahajanTimothy J. McDonald, Tarja Kokkola, Femke Rutters, Joline Beulens, Mirthe Muilwijk, Marieke Blom, Petra Elders, Tue H. Hansen, Juan Fernandez-Tajes, Angus Jones, Chris Jennison, Mark Walker, Mark I. McCarthy, Oluf Pedersen, Hartmut Ruetten, Ian Forgie, Jens J. Holst, Henrik S. Thomsen, Martin Ridderstråle, Jimmy D. Bell, Jerzy Adamski, Paul W. Franks, Torben Hansen, Elaine Holmes, Gary Frost*, Ewan R. Pearson*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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.

Original languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Volume109
Issue number9
Pages (from-to)e1697-e1707
ISSN0021-972X
DOIs
Publication statusPublished - 2024

Keywords

  • Cardiometabolic markers
  • Diet
  • GLP-1
  • Incretin
  • Insulin resistance
  • Liver fat
  • Nutrition
  • Obesity
  • Prediabetes
  • Type 2 diabetes

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