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^*

^*Corresponding author for this work

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
DOIs	https://doi.org/10.1210/clinem/dgae119
Publication status	Published - 1 Sept 2024
Externally published	Yes

Keywords

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

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10.1210/clinem/dgae119

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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

@article{050b0e4e375944c1a4458f50f64caf18,

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

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",

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.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.",

year = "2024",

month = sep,

day = "1",

doi = "10.1210/clinem/dgae119",

language = "English",

volume = "109",

pages = "e1697--e1707",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "9",

}

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

TY - JOUR

T1 - The Association of Cardiometabolic, Diet and Lifestyle Parameters With Plasma Glucagon-like Peptide-1

T2 - An IMI DIRECT Study

AU - Eriksen, Rebeca

AU - White, Margaret C.

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

AU - Elders, Petra

AU - Hansen, Tue H.

AU - Fernandez-Tajes, Juan

AU - Jones, Angus

AU - Jennison, Chris

AU - Walker, Mark

AU - McCarthy, Mark I.

AU - Pedersen, Oluf

AU - Ruetten, Hartmut

AU - Forgie, Ian

AU - Holst, Jens J.

AU - Thomsen, Henrik S.

AU - Ridderstråle, Martin

AU - Bell, Jimmy D.

AU - Adamski, Jerzy

AU - Franks, Paul W.

AU - Hansen, Torben

AU - Holmes, Elaine

AU - Frost, Gary

AU - Pearson, Ewan R.

PY - 2024/9/1

Y1 - 2024/9/1

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.

KW - GLP-1

KW - cardiometabolic markers

KW - diet

KW - incretin

KW - insulin resistance

KW - liver fat

KW - nutrition

KW - obesity

KW - prediabetes

KW - type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85201230805&partnerID=8YFLogxK

U2 - 10.1210/clinem/dgae119

DO - 10.1210/clinem/dgae119

M3 - Article

C2 - 38686701

AN - SCOPUS:85201230805

SN - 0021-972X

VL - 109

SP - e1697-e1707

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 9

ER -

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

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Keywords

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