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; Louise E 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 Mahajan; Timothy 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

doi:10.1210/clinem/dgae119

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

J Clin Endocrinol Metab. 2024 Apr 30:dgae119. doi: 10.1210/clinem/dgae119. Online ahead of print.

Authors

Rebeca Eriksen¹, Margaret C White², Adem Y Dawed², Isabel Garcia Perez¹, Joram M Posma^{3

4}, Mark Haid⁵, Sapna Sharma^{6

7}, Cornelia Prehn⁵, Louise E Thomas⁸, Robert W Koivula^{9

10}, Roberto Bizzotto¹¹, Andrea Mari¹¹, Giuseppe N Giordano⁹, Imre Pavo¹², Jochen M Schwenk¹³, Federico De Masi¹⁴, Konstantinos D Tsirigos¹⁴, Søren Brunak^{14

15}, Ana Viñuela¹⁶, Anubha Mahajan¹⁷, Timothy J McDonald¹⁸, Tarja Kokkola¹⁹, Femke Rutters²⁰, Joline Beulens²⁰, Mirthe Muilwijk²⁰, Marieke Blom²⁰, Petra Elders²⁰, Tue H Hansen²¹, Juan Fernandez-Tajes¹⁷, Angus Jones¹⁸, Chris Jennison²², Mark Walker²³, Mark I McCarthy^{10

17

24}, Oluf Pedersen²¹, Hartmut Ruetten²⁵, Ian Forgie², Jens J Holst^{21

26}, Henrik S Thomsen²⁷, Martin Ridderstråle²⁸, Jimmy D Bell⁸, Jerzy Adamski^{5

29

30}, Paul W Franks^{9

31}, Torben Hansen²¹, Elaine Holmes¹, Gary Frost¹, Ewan R Pearson²

Affiliations

¹ Section for Nutrition Research, Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, UK.
² Population Health & Genomics, School of Medicine, University of Dundee, Dundee, UK.
³ Section of Bioinformatics, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College, London, UK.
⁴ Health Data Research UK, London, UK.
⁵ Research Unit Molecular Endocrinology And Metabolism, Helmholtz Zentrum Muenchen, German Research Center for Environemental Health (GmbH), Neuherberg, Germany.
⁶ German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.
⁷ Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany.
⁸ Research Centre for Optimal Health, School of Life Sciences, University of Westminster, London, UK.
⁹ Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
¹⁰ Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Radcliffe Department of Medicine, Oxford, UK.
¹¹ Institute of Neuroscience - National Research Council, Padova, Italy.
¹² Eli Lilly Regional Operations GmbH, Vienna, Austria.
¹³ Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH - Royal Institute of Technology, Stockholm, Sweden.
¹⁴ Department of Health Technology, Technical University of Denmark, Kgs Lyngby and The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
¹⁵ Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, DK-2200 Copenhagen, Denmark.
¹⁶ Biosciences Institute, Newcastle University. Newcastle upon Tyne. United Kingdom.
¹⁷ Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
¹⁸ Medical School, Exeter, UK NIHR Exeter Clinical Research Facility, University of Exeter.
¹⁹ Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
²⁰ Department of Epidemiology and data Science, Amsterdam Public Health Institute, Amsterdam UMC, location VUMC, Amsterdam, The Netherlands.
²¹ The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.
²² Department of Mathematical Sciences, University of Bath, Bath, UK.
²³ Institute of Cellular Medicine (Diabetes), Newcastle University, Newcastle upon Tyne, UK.
²⁴ NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, UK.
²⁵ Sanofi-Aventis Deutschland GmbH, R&D, Frankfurt am Main, Germany.
²⁶ Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
²⁷ Faculty of Medical and Health Sciences, University of Copenhagen, Denmark.
²⁸ Novo Nordisk Fonden Tuborg Havnevej 19, 2900 Hellerup, Denmark.
²⁹ Lehrstuhl für Experimentelle Genetik, Technische Universität München, 85350 Freising-Weihenstephan, Germany.
³⁰ Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore.
³¹ Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America.

PMID: 38686701
DOI: 10.1210/clinem/dgae119

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.

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.