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
Number of pages	11
Journal	Journal of Clinical Endocrinology & Metabolism
Early online date	30 Apr 2024
DOIs	https://doi.org/10.1210/clinem/dgae119
Publication status	E-pub ahead of print - 30 Apr 2024

Keywords

Glp-1
Cardiometabolic markers
Diet
Incretin
Insulin resistance
Liver fat
Nutrition
Obesity
Prediabetes
Type 2 diabetes

UN SDGs

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

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10.1210/clinem/dgae119Licence: CC BY

Final published versionFinal published version, 648 KBLicence: CC BY

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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. 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, Article dgae119. Advance online publication. 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",

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 = apr,

day = "30",

doi = "10.1210/clinem/dgae119",

language = "English",

journal = "Journal of Clinical Endocrinology & Metabolism",

issn = "0021-972X",

publisher = "Endocrine Society",

}

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. 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 - 2024/4/30

Y1 - 2024/4/30

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

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U2 - 10.1210/clinem/dgae119

DO - 10.1210/clinem/dgae119

M3 - Article

C2 - 38686701

SN - 0021-972X

JO - Journal of Clinical Endocrinology & Metabolism

JF - Journal of Clinical Endocrinology & Metabolism

M1 - dgae119

ER -

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

Abstract

Keywords

UN SDGs

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