Glucagon-like peptide-1 secretion in people with versus without type 2 diabetes: A systematic review and meta-analysis of cross-sectional studies

Jon D. Watkins; Steven Carter; Greg Atkinson; Francoise Koumanov; James A. Betts; Jens Holst; Javier T. Gonzalez

doi:10.1016/j.metabol.2022.155375

Glucagon-like peptide-1 secretion in people with versus without type 2 diabetes: A systematic review and meta-analysis of cross-sectional studies

Jon D. Watkins, Steven Carter, Greg Atkinson, Francoise Koumanov, James A. Betts, Jens Holst, Javier T. Gonzalez

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Abstract

Aims/Hypothesis: The aim of this systematic review was to synthesise the study findings on whether GLP-1 secretion in response to a meal tolerance test is affected by the presence of type 2 diabetes (T2D). The influence of putative moderators such as age, sex, meal type, meal form, and assay type were also explored. Methods: A literature search identified 32 relevant studies. The sample mean and SD for fasting GLP-1 _TOTAL and GLP-1 _TOTAL iAUC were extracted and used to calculate between-group standardised mean differences (SMD), which were meta-analysed using a random-effects model to derive pooled estimates of Hedges' g and 95 % prediction intervals (PI). Results: Pooled across 18 studies, the overall SMD in GLP-1 _TOTAL iAUC between individuals with T2D (n = 270, 1047 ± 930 pmol·L ⁻¹·min) and individuals without T2D (n = 402, 1204 ± 937 pmol·L ⁻¹·min) was very small, not statistically significant and heterogenous across studies (g = −0.15, p = 0.43, PI: −1.53, 1.23). Subgroup analyses demonstrated an effect of assay type whereby Hedges' g for GLP-1 iAUC was greater in individuals with, versus those without T2D when using ELISA or Mesoscale (g = 0.67 [moderate], p = 0.009), but not when using RIA (g = −0.30 [small], p = 0.10). Pooled across 30 studies, the SMD in fasting GLP-1 _TOTAL between individuals with T2D (n = 580, 16.2 ± 6.9 pmol·L ⁻¹) versus individuals without T2D (n = 1363, 12.4 ± 5.7 pmol·L ⁻¹) was small and heterogenous between studies (g = 0.24, p = 0.21, PI: −1.55, 2.02). Conclusions: Differences in fasting GLP-1 _TOTAL and GLP-1 _TOTAL iAUC between individuals with, versus those without T2D were generally small and inconsistent between studies. Factors influencing study heterogeneity such as small sample sizes and poor matching of groups may help to explain the wide prediction intervals observed. Considerations to improve comparisons of GLP-1 secretion in T2D and potential mediating factors more important than T2D diagnosis per se are outlined. PROSPERO ID: CRD42020195612.

Original language	English
Article number	155375
Journal	Metabolism
Volume	140
Early online date	9 Dec 2022
DOIs	https://doi.org/10.1016/j.metabol.2022.155375
Publication status	Published - 31 Mar 2023

Bibliographical note

Arla Foods Ingredients Group P/S
part funded PhD

Funding Information:
JW has received research funding as part of their PhD studentship from Arla Foods Ingredients (DK). SC, and GA have no conflicts of interest. JJH is a member of the advisory board to Novo Nordisk. FK is supported by MRC (UK) funding (MR/P002927/1). JAB is an investigator on research grants funded by BBSRC, MRC, British Heart Foundation, Rare Disease Foundation, EU Hydration Institute, GlaxoSmithKline, Nestlé, Lucozade Ribena Suntory, ARLA foods, Kennis Centrum Suiker and Salus Optima (L3M Technologies Ltd); has completed paid consultancy for PepsiCo, Kellogg's, SVGC and Salus Optima (L3M Technologies Ltd); is Company Director of Metabolic Solutions Ltd.; receives an annual honorarium as a member of the academic advisory board for the International Olympic Committee Diploma in Sports Nutrition; and receives an annual stipend as Editor-in Chief of International Journal of Sport Nutrition & Exercise Metabolism. J.T.G. is an investigator on research grants funded by BBSRC, MRC, British Heart Foundation, The Rank Prize Funds, The European Society for Clinical Nutrition and Metabolism (ESPEN), Lucozade Ribena Suntory, ARLA Foods Ingredients, Kenniscentrum Suiker and Voeding and Clasado Biosciences; and has completed paid consultancy for PepsiCo and SVGC.

Keywords

Endocrinology
Glucagon-like peptide-1
Meta-analysis
Type 2 diabetes

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Endocrinology

UN SDGs

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

Access to Document

10.1016/j.metabol.2022.155375Licence: CC BY

GLP-1 Meta-analysis manuscript_3.11.22Accepted author manuscript, 2.09 MBLicence: CC BY

Cite this

@article{29754c8d84af47bd8991f1526f0826c1,

title = "Glucagon-like peptide-1 secretion in people with versus without type 2 diabetes: A systematic review and meta-analysis of cross-sectional studies",

abstract = "Aims/Hypothesis: The aim of this systematic review was to synthesise the study findings on whether GLP-1 secretion in response to a meal tolerance test is affected by the presence of type 2 diabetes (T2D). The influence of putative moderators such as age, sex, meal type, meal form, and assay type were also explored. Methods: A literature search identified 32 relevant studies. The sample mean and SD for fasting GLP-1 TOTAL and GLP-1 TOTAL iAUC were extracted and used to calculate between-group standardised mean differences (SMD), which were meta-analysed using a random-effects model to derive pooled estimates of Hedges' g and 95 % prediction intervals (PI). Results: Pooled across 18 studies, the overall SMD in GLP-1 TOTAL iAUC between individuals with T2D (n = 270, 1047 ± 930 pmol·L −1·min) and individuals without T2D (n = 402, 1204 ± 937 pmol·L −1·min) was very small, not statistically significant and heterogenous across studies (g = −0.15, p = 0.43, PI: −1.53, 1.23). Subgroup analyses demonstrated an effect of assay type whereby Hedges' g for GLP-1 iAUC was greater in individuals with, versus those without T2D when using ELISA or Mesoscale (g = 0.67 [moderate], p = 0.009), but not when using RIA (g = −0.30 [small], p = 0.10). Pooled across 30 studies, the SMD in fasting GLP-1 TOTAL between individuals with T2D (n = 580, 16.2 ± 6.9 pmol·L −1) versus individuals without T2D (n = 1363, 12.4 ± 5.7 pmol·L −1) was small and heterogenous between studies (g = 0.24, p = 0.21, PI: −1.55, 2.02). Conclusions: Differences in fasting GLP-1 TOTAL and GLP-1 TOTAL iAUC between individuals with, versus those without T2D were generally small and inconsistent between studies. Factors influencing study heterogeneity such as small sample sizes and poor matching of groups may help to explain the wide prediction intervals observed. Considerations to improve comparisons of GLP-1 secretion in T2D and potential mediating factors more important than T2D diagnosis per se are outlined. PROSPERO ID: CRD42020195612.",

keywords = "Endocrinology, Glucagon-like peptide-1, Meta-analysis, Type 2 diabetes",

author = "Watkins, {Jon D.} and Steven Carter and Greg Atkinson and Francoise Koumanov and Betts, {James A.} and Jens Holst and Gonzalez, {Javier T.}",

note = "Arla Foods Ingredients Group P/S part funded PhD Funding Information: JW has received research funding as part of their PhD studentship from Arla Foods Ingredients (DK). SC, and GA have no conflicts of interest. JJH is a member of the advisory board to Novo Nordisk. FK is supported by MRC (UK) funding (MR/P002927/1). JAB is an investigator on research grants funded by BBSRC, MRC, British Heart Foundation, Rare Disease Foundation, EU Hydration Institute, GlaxoSmithKline, Nestl{\'e}, Lucozade Ribena Suntory, ARLA foods, Kennis Centrum Suiker and Salus Optima (L3M Technologies Ltd); has completed paid consultancy for PepsiCo, Kellogg's, SVGC and Salus Optima (L3M Technologies Ltd); is Company Director of Metabolic Solutions Ltd.; receives an annual honorarium as a member of the academic advisory board for the International Olympic Committee Diploma in Sports Nutrition; and receives an annual stipend as Editor-in Chief of International Journal of Sport Nutrition & Exercise Metabolism. J.T.G. is an investigator on research grants funded by BBSRC, MRC, British Heart Foundation, The Rank Prize Funds, The European Society for Clinical Nutrition and Metabolism (ESPEN), Lucozade Ribena Suntory, ARLA Foods Ingredients, Kenniscentrum Suiker and Voeding and Clasado Biosciences; and has completed paid consultancy for PepsiCo and SVGC. ",

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doi = "10.1016/j.metabol.2022.155375",

language = "English",

volume = "140",

journal = "Metabolism",

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TY - JOUR

T1 - Glucagon-like peptide-1 secretion in people with versus without type 2 diabetes: A systematic review and meta-analysis of cross-sectional studies

AU - Watkins, Jon D.

AU - Carter, Steven

AU - Atkinson, Greg

AU - Koumanov, Francoise

AU - Betts, James A.

AU - Holst, Jens

AU - Gonzalez, Javier T.

N1 - Arla Foods Ingredients Group P/S part funded PhD Funding Information: JW has received research funding as part of their PhD studentship from Arla Foods Ingredients (DK). SC, and GA have no conflicts of interest. JJH is a member of the advisory board to Novo Nordisk. FK is supported by MRC (UK) funding (MR/P002927/1). JAB is an investigator on research grants funded by BBSRC, MRC, British Heart Foundation, Rare Disease Foundation, EU Hydration Institute, GlaxoSmithKline, Nestlé, Lucozade Ribena Suntory, ARLA foods, Kennis Centrum Suiker and Salus Optima (L3M Technologies Ltd); has completed paid consultancy for PepsiCo, Kellogg's, SVGC and Salus Optima (L3M Technologies Ltd); is Company Director of Metabolic Solutions Ltd.; receives an annual honorarium as a member of the academic advisory board for the International Olympic Committee Diploma in Sports Nutrition; and receives an annual stipend as Editor-in Chief of International Journal of Sport Nutrition & Exercise Metabolism. J.T.G. is an investigator on research grants funded by BBSRC, MRC, British Heart Foundation, The Rank Prize Funds, The European Society for Clinical Nutrition and Metabolism (ESPEN), Lucozade Ribena Suntory, ARLA Foods Ingredients, Kenniscentrum Suiker and Voeding and Clasado Biosciences; and has completed paid consultancy for PepsiCo and SVGC.

PY - 2023/3/31

Y1 - 2023/3/31

N2 - Aims/Hypothesis: The aim of this systematic review was to synthesise the study findings on whether GLP-1 secretion in response to a meal tolerance test is affected by the presence of type 2 diabetes (T2D). The influence of putative moderators such as age, sex, meal type, meal form, and assay type were also explored. Methods: A literature search identified 32 relevant studies. The sample mean and SD for fasting GLP-1 TOTAL and GLP-1 TOTAL iAUC were extracted and used to calculate between-group standardised mean differences (SMD), which were meta-analysed using a random-effects model to derive pooled estimates of Hedges' g and 95 % prediction intervals (PI). Results: Pooled across 18 studies, the overall SMD in GLP-1 TOTAL iAUC between individuals with T2D (n = 270, 1047 ± 930 pmol·L −1·min) and individuals without T2D (n = 402, 1204 ± 937 pmol·L −1·min) was very small, not statistically significant and heterogenous across studies (g = −0.15, p = 0.43, PI: −1.53, 1.23). Subgroup analyses demonstrated an effect of assay type whereby Hedges' g for GLP-1 iAUC was greater in individuals with, versus those without T2D when using ELISA or Mesoscale (g = 0.67 [moderate], p = 0.009), but not when using RIA (g = −0.30 [small], p = 0.10). Pooled across 30 studies, the SMD in fasting GLP-1 TOTAL between individuals with T2D (n = 580, 16.2 ± 6.9 pmol·L −1) versus individuals without T2D (n = 1363, 12.4 ± 5.7 pmol·L −1) was small and heterogenous between studies (g = 0.24, p = 0.21, PI: −1.55, 2.02). Conclusions: Differences in fasting GLP-1 TOTAL and GLP-1 TOTAL iAUC between individuals with, versus those without T2D were generally small and inconsistent between studies. Factors influencing study heterogeneity such as small sample sizes and poor matching of groups may help to explain the wide prediction intervals observed. Considerations to improve comparisons of GLP-1 secretion in T2D and potential mediating factors more important than T2D diagnosis per se are outlined. PROSPERO ID: CRD42020195612.

AB - Aims/Hypothesis: The aim of this systematic review was to synthesise the study findings on whether GLP-1 secretion in response to a meal tolerance test is affected by the presence of type 2 diabetes (T2D). The influence of putative moderators such as age, sex, meal type, meal form, and assay type were also explored. Methods: A literature search identified 32 relevant studies. The sample mean and SD for fasting GLP-1 TOTAL and GLP-1 TOTAL iAUC were extracted and used to calculate between-group standardised mean differences (SMD), which were meta-analysed using a random-effects model to derive pooled estimates of Hedges' g and 95 % prediction intervals (PI). Results: Pooled across 18 studies, the overall SMD in GLP-1 TOTAL iAUC between individuals with T2D (n = 270, 1047 ± 930 pmol·L −1·min) and individuals without T2D (n = 402, 1204 ± 937 pmol·L −1·min) was very small, not statistically significant and heterogenous across studies (g = −0.15, p = 0.43, PI: −1.53, 1.23). Subgroup analyses demonstrated an effect of assay type whereby Hedges' g for GLP-1 iAUC was greater in individuals with, versus those without T2D when using ELISA or Mesoscale (g = 0.67 [moderate], p = 0.009), but not when using RIA (g = −0.30 [small], p = 0.10). Pooled across 30 studies, the SMD in fasting GLP-1 TOTAL between individuals with T2D (n = 580, 16.2 ± 6.9 pmol·L −1) versus individuals without T2D (n = 1363, 12.4 ± 5.7 pmol·L −1) was small and heterogenous between studies (g = 0.24, p = 0.21, PI: −1.55, 2.02). Conclusions: Differences in fasting GLP-1 TOTAL and GLP-1 TOTAL iAUC between individuals with, versus those without T2D were generally small and inconsistent between studies. Factors influencing study heterogeneity such as small sample sizes and poor matching of groups may help to explain the wide prediction intervals observed. Considerations to improve comparisons of GLP-1 secretion in T2D and potential mediating factors more important than T2D diagnosis per se are outlined. PROSPERO ID: CRD42020195612.

KW - Endocrinology

KW - Glucagon-like peptide-1

KW - Meta-analysis

KW - Type 2 diabetes

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DO - 10.1016/j.metabol.2022.155375

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ER -

Glucagon-like peptide-1 secretion in people with versus without type 2 diabetes: A systematic review and meta-analysis of cross-sectional studies

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Role of Rab3 in Peripheral Tissue Insulin Resistance

Cite this

Glucagon-like peptide-1 secretion in people with versus without type 2 diabetes: A systematic review and meta-analysis of cross-sectional studies

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

Role of Rab3 in Peripheral Tissue Insulin Resistance

Cite this