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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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