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. 2024 Aug 13;109(9):e1697-e1707.
doi: 10.1210/clinem/dgae119.

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

Rebeca Eriksen  1 , Margaret C White  2 , Adem Y Dawed  2 , Isabel Garcia Perez  1 , Joram M Posma  3   4 , Mark Haid  5 , Sapna Sharma  6   7 , Cornelia Prehn  5 , E Louise Thomas  8 , Robert W Koivula  9   10 , Roberto Bizzotto  11 , Andrea Mari  11 , Giuseppe N Giordano  9 , Imre Pavo  12 , Jochen M Schwenk  13 , Federico De Masi  14 , Konstantinos D Tsirigos  14 , Søren Brunak  14   15 , Ana Viñuela  16 , Anubha Mahajan  17 , Timothy J McDonald  18 , Tarja Kokkola  19 , Femke Rutters  20 , Joline Beulens  20 , Mirthe Muilwijk  20 , Marieke Blom  20 , Petra Elders  20 , Tue H Hansen  21 , Juan Fernandez-Tajes  17 , Angus Jones  18 , Chris Jennison  22 , Mark Walker  23 , Mark I McCarthy  10   17   24 , Oluf Pedersen  21 , Hartmut Ruetten  25 , Ian Forgie  2 , Jens J Holst  21   26 , Henrik S Thomsen  27 , Martin Ridderstråle  28 , Jimmy D Bell  8 , Jerzy Adamski  5   29   30 , Paul W Franks  9   31 , Torben Hansen  21 , Elaine Holmes  1 , Gary Frost  1 , Ewan R Pearson  2
Affiliations

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

Rebeca Eriksen et al. J Clin Endocrinol Metab. .

Erratum in

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.

Keywords: GLP-1; cardiometabolic markers; diet; incretin; insulin resistance; liver fat; nutrition; obesity; prediabetes; type 2 diabetes.

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Figures

Figure 1.
Figure 1.
Independent effects of age, sex, body mass index (BMI), glucose tolerance, lipids, alcohol, center, and metformin in the baseline model for total glucagon-like peptide-1 (GLP-1). Diagrammatic representation of the multivariable baseline regression model (Supplementary Table S12 (17)). Percentage (%) difference represents percentage changes in total GLP-1 per one-unit change in independent variable adjusted for other model covariates: age, sex, BMI, glucose tolerance (cohort 1 only), lipids, alcohol, and center. Black = fasting total GLP-1, (cohort 1, n = 2226; cohort 2, n = 739). Blue = incremental total GLP-1 (cohort 1, n = 2207; cohort 2, n = 739). A, Data from cohort 1 = participants with a range of prediabetes glucose tolerances, including impaired fasting glucose (IFG), impaired glucose tolerance (IGT), both IFG and IGT (IFG & IGT), and those with screen-detected type 2 diabetes (SD-DM). B, Data from cohort 2 = participants with type 2 diabetes. Reference groups = normal glucose tolerance for IFG, IGT, IFG & IGT, and SD-DM. Normal weight for obesity and overweight, no alcohol intake for occasional, and regular alcohol status.
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