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Eriksen, R.* ; White, M.C.* ; Dawed, A.Y.* ; Garcia Perez, I.* ; Posma, J.M.* ; Haid, M. ; Sharma, S. ; Prehn, C. ; Thomas, L.E.* ; Koivula, R.W.* ; Bizzotto, R.* ; Mari, A.* ; Giordano, G.N.* ; Pavo, I.* ; Schwenk, J.M.* ; De Masi, F.* ; Tsirigos, K.D.* ; Brunak, S.* ; Viñuela, A.* ; Mahajan, A.* ; McDonald, T.J.* ; Kokkola, T.* ; Rutters, F.* ; Beulens, J.* ; Muilwijk, M.* ; Blom, M.T.* ; Elders, P.* ; Hansen, T.H.* ; Fernandez-Tajes, J.* ; Jones, A.* ; Jennison, C.* ; Walker, M.* ; McCarthy, M.I.* ; Pedersen, O.* ; Ruetten, H.* ; Forgie, I.* ; Holst, J.J.* ; Thomsen, H.S.* ; Ridderstråle, M.* ; Bell, J.D.* ; Adamski, J. ; Franks, P.W.* ; Hansen, T.* ; Holmes, E.* ; Frost, G.* ; Pearson, E.R.*

The association of cardiometabolic, diet and lifestyle parameters with plasma glucagon-like peptide-1: An IMI DIRECT study.

J. Clin. Endocrinol. Metab. 109, e1697-e1707 (2024)

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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. METHOD: We analysed 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 of 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 glycaemia, 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 inpeople 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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords GLP-1; type 2 diabetes; prediabetes; liver fat; obesity; insulin resistance; incretin; nutrition; diet; cardiometabolic markers; Mixed Meal; Glp-1; Secretion; Discovery; Cells; Risk

ISSN (print) / ISBN 0021-972X

e-ISSN 1945-7197

Journal Journal of Clinical Endocrinology & Metabolism, The

Quellenangaben Volume: 109, Issue: 9, Pages: e1697-e1707

Publisher Endocrine Society

Publishing Place Bethesda, Md.

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Epidemiology (EPI)

Grants
Wellcome
Rutherford Fund Fellowship at Health Data Research (HDR) UK
NIHR Fellowship
Imperial College National Institute for Health Research (NIHR) BRC
European Union
Novo Nordisk Foundation
Swedish Research Council, Linnaeus
Swedish Foundation for Strategic Research
Lund University Diabetes Centre
Swedish Research Council
STAR Award Novo Nordisk
NIHR (Niddk)
Innovative Medicines Initiative Joint Undertaking