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 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 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 (Lead / Corresponding author), Ewan R Pearson (Lead / Corresponding author)

Population Health and Genomics

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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.

Original language	English
Article number	dgae119
Pages (from-to)	e1697-e1707
Number of pages	11
Journal	Journal of Clinical Endocrinology & 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

Keywords

Glp-1
Cardiometabolic markers
Diet
Incretin
Insulin resistance
Liver fat
Nutrition
Obesity
Prediabetes
Type 2 diabetes
cardiometabolic markers
GLP-1
incretin
prediabetes
nutrition
type 2 diabetes
liver fat
diet
insulin resistance
obesity

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)

Access to Document

10.1210/clinem/dgae119Licence: CC BY

Final published versionFinal published version, 649 KBLicence: CC BY

Cite this

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. D., 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 & Metabolism, 109(9), e1697-e1707. Article dgae119. https://doi.org/10.1210/clinem/dgae119

@article{37d0b3bb9e8249f6800aa6bcd9b7e495,

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

abstract = "ContextThe role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes (T2D) and obesity is not fully understood.ObjectiveWe investigate the association of cardiometabolic, diet, and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D.MethodsWe 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.ResultsOur 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.ConclusionThese 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, cardiometabolic markers, GLP-1, incretin, prediabetes, nutrition, type 2 diabetes, liver fat, diet, insulin resistance, obesity",

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 De} 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 = "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 & Metabolism",

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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, FD, 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 & Metabolism, vol. 109, no. 9, dgae119, 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 De

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 - ContextThe role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes (T2D) and obesity is not fully understood.ObjectiveWe investigate the association of cardiometabolic, diet, and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D.MethodsWe 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.ResultsOur 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.ConclusionThese 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 - ContextThe role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes (T2D) and obesity is not fully understood.ObjectiveWe investigate the association of cardiometabolic, diet, and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D.MethodsWe 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.ResultsOur 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.ConclusionThese 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

KW - cardiometabolic markers

KW - GLP-1

KW - incretin

KW - prediabetes

KW - nutrition

KW - type 2 diabetes

KW - liver fat

KW - diet

KW - insulin resistance

KW - obesity

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

DIRECT: Diabetes Research on Patient Stratification (joint with 25 other partners)

Stratified Medicine in Type 2 Diabetes: Insights from the Study of Drug Response (New Investigator Award)

Cite this

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

DIRECT: Diabetes Research on Patient Stratification (joint with 25 other partners)

Stratified Medicine in Type 2 Diabetes: Insights from the Study of Drug Response (New Investigator Award)

Cite this