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; E. Louise 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

Rebeca Eriksen, Margaret C. White, Adem Y. Dawed, Isabel Garcia Perez, Joram M. Posma, Mark Haid, Sapna Sharma, Cornelia Prehn, E. Louise 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 MahajanTimothy 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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	e1697-e1707
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	109
Issue number	9
Early online date	30 Apr 2024
DOIs	https://doi.org/10.1210/clinem/dgae119
Publication status	Published - 1 Sept 2024

Data Availability Statement

This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement number 115317 (DIRECT), resources of which are composed of a financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in-kind contribution. G.F. was funded by Imperial College National Institute for Health Research (NIHR) BRC and is an NIHR senior investigator. I.G.-P. is supported by an NIHR Fellowship (NIHR-CDF-2017-10-032). J.M.P. is supported by a Rutherford Fund Fellowship at Health Data Research (HDR) UK (MR/S004033/1). M.Mc.C. was a Wellcome Investigator (090532, 098381, 106130, 203141, 2122590 and an NIHR Senior Investigator (Niddk. U01-DK105535). R.W.K. was funded by a STAR Award Novo Nordisk-cofinanced PhD fellowship. This work was supported in part by ERC-2015-CoG_NASCENT_681742 and the Swedish Research Council; strategic funding for Lund University Diabetes Centre, where some of the work described herein was performed, was provided by the Swedish Research Council, Strategic Research Area Exodiab, (Dnr 2009-1039), the Swedish Foundation for Strategic Research (IRC15-0067), the Swedish Research Council, Linnaeus grant (Dnr 349-2006-237). E.P. holds a Wellcome Trust Investigator award (grant reference 102820/Z/13/Z). Contributions to this work by S.Bru were cofinanced by the Novo Nordisk Foundation (grant Nos. NNF17OC0027594 and NNF14CC0001).

Acknowledgements

We thank the participants across all IMI DIRECT Study centers for their contributions to the study. We also thank all the staff for their contribution to the planning, implementation, or conduct of the study: http://www.direct-diabetes.org/.

Keywords

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

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Biochemistry
Endocrinology
Clinical Biochemistry
Biochemistry, medical

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Eriksen, R., White, M. C., Dawed, A. Y., Perez, I. G., Posma, J. M., Haid, M., Sharma, S., Prehn, C., Thomas, E. L., 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., ... Pearson, E. R. (2024). The Association of Cardiometabolic, Diet and Lifestyle Parameters With Plasma Glucagon-like Peptide-1: An IMI DIRECT Study. Journal of Clinical Endocrinology and Metabolism, 109(9), e1697-e1707. https://doi.org/10.1210/clinem/dgae119

Eriksen, R, White, MC, Dawed, AY, Perez, IG, Posma, JM, Haid, M, Sharma, S, Prehn, C, Thomas, EL, Koivula, RW, Bizzotto, R, Mari, A, Giordano, GN, Pavo, I, Schwenk, JM, De Masi, F, Tsirigos, KD, Brunak, S, Viñuela, A, Mahajan, A, McDonald, TJ, Kokkola, T, Rutters, F, Beulens, J, Muilwijk, M, Blom, M, Elders, P, Hansen, TH, Fernandez-Tajes, J, Jones, A, Jennison, C, Walker, M, McCarthy, MI, Pedersen, O, Ruetten, H, Forgie, I, Holst, JJ, Thomsen, HS, Ridderstråle, M, Bell, JD, Adamski, J, Franks, PW, Hansen, T, Holmes, E, Frost, G & Pearson, ER 2024, 'The Association of Cardiometabolic, Diet and Lifestyle Parameters With Plasma Glucagon-like Peptide-1: An IMI DIRECT Study', Journal of Clinical Endocrinology and Metabolism, vol. 109, no. 9, pp. e1697-e1707. https://doi.org/10.1210/clinem/dgae119

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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 = "cardiometabolic markers, diet, GLP-1, incretin, insulin resistance, liver fat, nutrition, obesity, prediabetes, type 2 diabetes",

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

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AU - Dawed, Adem Y.

AU - Perez, Isabel Garcia

AU - Posma, Joram M.

AU - Haid, Mark

AU - Sharma, Sapna

AU - Prehn, Cornelia

AU - Thomas, E. Louise

AU - Koivula, Robert W.

AU - Bizzotto, Roberto

AU - Mari, Andrea

AU - Giordano, Giuseppe N.

AU - Pavo, Imre

AU - Schwenk, Jochen M.

AU - De Masi, Federico

AU - Tsirigos, Konstantinos D.

AU - Brunak, Søren

AU - Viñuela, Ana

AU - Mahajan, Anubha

AU - McDonald, Timothy J.

AU - Kokkola, Tarja

AU - Rutters, Femke

AU - Beulens, Joline

AU - Muilwijk, Mirthe

AU - Blom, Marieke

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AU - Hansen, Tue H.

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AU - Holst, Jens J.

AU - Thomsen, Henrik S.

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AU - Bell, Jimmy D.

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AU - Franks, Paul W.

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AU - Holmes, Elaine

AU - Frost, Gary

AU - Pearson, Ewan R.

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N2 - 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.

AB - 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.

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

Abstract

Data Availability Statement

Acknowledgements

Keywords

ASJC Scopus subject areas

UN SDGs

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