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