Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes: An IMI-DIRECT study

Morgan Obura; Joline W. J. Beulens; Roderick Slieker; Anitra D. M. Koopman; Trynke Hoekstra; Giel Nijpels; Petra Elders; Robert W. Koivula; Azra Kurbasic; Markku Laakso; Tue H. Hansen; Martin Ridderstråle; Torben Hansen; Imre Pavo; Ian Forgie; Bernd Jablonka; Hartmut Ruetten; Andrea Mari; Mark I. McCarthy; Mark Walker; Alison Heggie; Timothy J. McDonald; Mandy H. Perry; Federico De Masi; Søren Brunak; Anubha Mahajan; Giuseppe N. Giordano; Tarja Kokkola; Emmanouil Dermitzakis; Ana Viñuela; Oluf Pedersen; Jochen M. Schwenk; Jurek Adamski; Harriet J.A. Teare; Ewan R. Pearson; Paul W. Franks; Leen M. 't Hart; Femke Rutters; IMI DIRECT Consortium

doi:10.1371/journal.pone.0242360

Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes: An IMI-DIRECT study

Morgan Obura, Joline W. J. Beulens (Lead / Corresponding author), Roderick Slieker, Anitra D. M. Koopman, Trynke Hoekstra, Giel Nijpels, Petra Elders, Robert W. Koivula, Azra Kurbasic, Markku Laakso, Tue H. Hansen, Martin Ridderstråle, Torben Hansen, Imre Pavo, Ian Forgie, Bernd Jablonka, Hartmut Ruetten, Andrea Mari, Mark I. McCarthy, Mark WalkerAlison Heggie, Timothy J. McDonald, Mandy H. Perry, Federico De Masi, Søren Brunak, Anubha Mahajan, Giuseppe N. Giordano, Tarja Kokkola, Emmanouil Dermitzakis, Ana Viñuela, Oluf Pedersen, Jochen M. Schwenk, Jurek Adamski, Harriet J.A. Teare, Ewan R. Pearson, Paul W. Franks, Leen M. 't Hart, Femke Rutters, IMI DIRECT Consortium

Population Health and Genomics

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Abstract

Aim: Subclasses of different glycaemic disturbances could explain the variation in characteristics of individuals with type 2 diabetes (T2D). We aimed to examine the association between subgroups based on their glucose curves during a five-point mixed-meal tolerance test (MMT) and metabolic traits at baseline and glycaemic deterioration in individuals with T2D.

Methods: The study included 787 individuals with newly diagnosed T2D from the Diabetes Research on Patient Stratification (IMI-DIRECT) Study. Latent class trajectory analysis (LCTA) was used to identify distinct glucose curve subgroups during a five-point MMT. Using general linear models, these subgroups were associated with metabolic traits at baseline and after 18 months of follow up, adjusted for potential confounders.

Results: At baseline, we identified three glucose curve subgroups, labelled in order of increasing glucose peak levels as subgroup 1-3. Individuals in subgroup 2 and 3 were more likely to have higher levels of HbA1c, triglycerides and BMI at baseline, compared to those in subgroup 1. At 18 months (n = 651), the beta coefficients (95% CI) for change in HbA1c (mmol/mol) increased across subgroups with 0.37 (-0.18-1.92) for subgroup 2 and 1.88 (-0.08-3.85) for subgroup 3, relative to subgroup 1. The same trend was observed for change in levels of triglycerides and fasting glucose.

Conclusions: Different glycaemic profiles with different metabolic traits and different degrees of subsequent glycaemic deterioration can be identified using data from a frequently sampled mixed-meal tolerance test in individuals with T2D. Subgroups with the highest peaks had greater metabolic risk.

Original language	English
Article number	e0242360
Number of pages	11
Journal	PLoS ONE
Volume	15
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0242360
Publication status	Published - 30 Nov 2020

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology
General Agricultural and Biological Sciences
General

UN SDGs

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

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10.1371/journal.pone.0242360Licence: CC0

Final Published VersionFinal published version, 661 KBLicence: CC0

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Obura, M., Beulens, J. W. J., Slieker, R., Koopman, A. D. M., Hoekstra, T., Nijpels, G., Elders, P., Koivula, R. W., Kurbasic, A., Laakso, M., Hansen, T. H., Ridderstråle, M., Hansen, T., Pavo, I., Forgie, I., Jablonka, B., Ruetten, H., Mari, A., McCarthy, M. I., ... IMI DIRECT Consortium (2020). Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes: An IMI-DIRECT study. PLoS ONE, 15(11), Article e0242360. https://doi.org/10.1371/journal.pone.0242360

@article{930a5979145746c2b58e3a1533eca0c9,

title = "Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes: An IMI-DIRECT study",

abstract = "Aim: Subclasses of different glycaemic disturbances could explain the variation in characteristics of individuals with type 2 diabetes (T2D). We aimed to examine the association between subgroups based on their glucose curves during a five-point mixed-meal tolerance test (MMT) and metabolic traits at baseline and glycaemic deterioration in individuals with T2D.Methods: The study included 787 individuals with newly diagnosed T2D from the Diabetes Research on Patient Stratification (IMI-DIRECT) Study. Latent class trajectory analysis (LCTA) was used to identify distinct glucose curve subgroups during a five-point MMT. Using general linear models, these subgroups were associated with metabolic traits at baseline and after 18 months of follow up, adjusted for potential confounders.Results: At baseline, we identified three glucose curve subgroups, labelled in order of increasing glucose peak levels as subgroup 1-3. Individuals in subgroup 2 and 3 were more likely to have higher levels of HbA1c, triglycerides and BMI at baseline, compared to those in subgroup 1. At 18 months (n = 651), the beta coefficients (95% CI) for change in HbA1c (mmol/mol) increased across subgroups with 0.37 (-0.18-1.92) for subgroup 2 and 1.88 (-0.08-3.85) for subgroup 3, relative to subgroup 1. The same trend was observed for change in levels of triglycerides and fasting glucose.Conclusions: Different glycaemic profiles with different metabolic traits and different degrees of subsequent glycaemic deterioration can be identified using data from a frequently sampled mixed-meal tolerance test in individuals with T2D. Subgroups with the highest peaks had greater metabolic risk.",

author = "Morgan Obura and Beulens, {Joline W. J.} and Roderick Slieker and Koopman, {Anitra D. M.} and Trynke Hoekstra and Giel Nijpels and Petra Elders and Koivula, {Robert W.} and Azra Kurbasic and Markku Laakso and Hansen, {Tue H.} and Martin Ridderstr{\aa}le and Torben Hansen and Imre Pavo and Ian Forgie and Bernd Jablonka and Hartmut Ruetten and Andrea Mari and McCarthy, {Mark I.} and Mark Walker and Alison Heggie and McDonald, {Timothy J.} and Perry, {Mandy H.} and {De Masi}, Federico and S{\o}ren Brunak and Anubha Mahajan and Giordano, {Giuseppe N.} and Tarja Kokkola and Emmanouil Dermitzakis and Ana Vi{\~n}uela and Oluf Pedersen and Schwenk, {Jochen M.} and Jurek Adamski and Teare, {Harriet J.A.} and Pearson, {Ewan R.} and Franks, {Paul W.} and {'t Hart}, {Leen M.} and Femke Rutters and {IMI DIRECT Consortium}",

note = "Funding: Innovative Medicines Initiative (n°115317)",

year = "2020",

month = nov,

day = "30",

doi = "10.1371/journal.pone.0242360",

language = "English",

volume = "15",

journal = "PLoS ONE",

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Obura, M, Beulens, JWJ, Slieker, R, Koopman, ADM, Hoekstra, T, Nijpels, G, Elders, P, Koivula, RW, Kurbasic, A, Laakso, M, Hansen, TH, Ridderstråle, M, Hansen, T, Pavo, I, Forgie, I, Jablonka, B, Ruetten, H, Mari, A, McCarthy, MI, Walker, M, Heggie, A, McDonald, TJ, Perry, MH, De Masi, F, Brunak, S, Mahajan, A, Giordano, GN, Kokkola, T, Dermitzakis, E, Viñuela, A, Pedersen, O, Schwenk, JM, Adamski, J, Teare, HJA, Pearson, ER, Franks, PW, 't Hart, LM, Rutters, F & IMI DIRECT Consortium 2020, 'Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes: An IMI-DIRECT study', PLoS ONE, vol. 15, no. 11, e0242360. https://doi.org/10.1371/journal.pone.0242360

TY - JOUR

T1 - Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes

T2 - An IMI-DIRECT study

AU - Obura, Morgan

AU - Beulens, Joline W. J.

AU - Slieker, Roderick

AU - Koopman, Anitra D. M.

AU - Hoekstra, Trynke

AU - Nijpels, Giel

AU - Elders, Petra

AU - Koivula, Robert W.

AU - Kurbasic, Azra

AU - Laakso, Markku

AU - Hansen, Tue H.

AU - Ridderstråle, Martin

AU - Hansen, Torben

AU - Pavo, Imre

AU - Forgie, Ian

AU - Jablonka, Bernd

AU - Ruetten, Hartmut

AU - Mari, Andrea

AU - McCarthy, Mark I.

AU - Walker, Mark

AU - Heggie, Alison

AU - McDonald, Timothy J.

AU - Perry, Mandy H.

AU - De Masi, Federico

AU - Brunak, Søren

AU - Mahajan, Anubha

AU - Giordano, Giuseppe N.

AU - Kokkola, Tarja

AU - Dermitzakis, Emmanouil

AU - Viñuela, Ana

AU - Pedersen, Oluf

AU - Schwenk, Jochen M.

AU - Adamski, Jurek

AU - Teare, Harriet J.A.

AU - Pearson, Ewan R.

AU - Franks, Paul W.

AU - 't Hart, Leen M.

AU - Rutters, Femke

AU - IMI DIRECT Consortium

N1 - Funding: Innovative Medicines Initiative (n°115317)

PY - 2020/11/30

Y1 - 2020/11/30

N2 - Aim: Subclasses of different glycaemic disturbances could explain the variation in characteristics of individuals with type 2 diabetes (T2D). We aimed to examine the association between subgroups based on their glucose curves during a five-point mixed-meal tolerance test (MMT) and metabolic traits at baseline and glycaemic deterioration in individuals with T2D.Methods: The study included 787 individuals with newly diagnosed T2D from the Diabetes Research on Patient Stratification (IMI-DIRECT) Study. Latent class trajectory analysis (LCTA) was used to identify distinct glucose curve subgroups during a five-point MMT. Using general linear models, these subgroups were associated with metabolic traits at baseline and after 18 months of follow up, adjusted for potential confounders.Results: At baseline, we identified three glucose curve subgroups, labelled in order of increasing glucose peak levels as subgroup 1-3. Individuals in subgroup 2 and 3 were more likely to have higher levels of HbA1c, triglycerides and BMI at baseline, compared to those in subgroup 1. At 18 months (n = 651), the beta coefficients (95% CI) for change in HbA1c (mmol/mol) increased across subgroups with 0.37 (-0.18-1.92) for subgroup 2 and 1.88 (-0.08-3.85) for subgroup 3, relative to subgroup 1. The same trend was observed for change in levels of triglycerides and fasting glucose.Conclusions: Different glycaemic profiles with different metabolic traits and different degrees of subsequent glycaemic deterioration can be identified using data from a frequently sampled mixed-meal tolerance test in individuals with T2D. Subgroups with the highest peaks had greater metabolic risk.

AB - Aim: Subclasses of different glycaemic disturbances could explain the variation in characteristics of individuals with type 2 diabetes (T2D). We aimed to examine the association between subgroups based on their glucose curves during a five-point mixed-meal tolerance test (MMT) and metabolic traits at baseline and glycaemic deterioration in individuals with T2D.Methods: The study included 787 individuals with newly diagnosed T2D from the Diabetes Research on Patient Stratification (IMI-DIRECT) Study. Latent class trajectory analysis (LCTA) was used to identify distinct glucose curve subgroups during a five-point MMT. Using general linear models, these subgroups were associated with metabolic traits at baseline and after 18 months of follow up, adjusted for potential confounders.Results: At baseline, we identified three glucose curve subgroups, labelled in order of increasing glucose peak levels as subgroup 1-3. Individuals in subgroup 2 and 3 were more likely to have higher levels of HbA1c, triglycerides and BMI at baseline, compared to those in subgroup 1. At 18 months (n = 651), the beta coefficients (95% CI) for change in HbA1c (mmol/mol) increased across subgroups with 0.37 (-0.18-1.92) for subgroup 2 and 1.88 (-0.08-3.85) for subgroup 3, relative to subgroup 1. The same trend was observed for change in levels of triglycerides and fasting glucose.Conclusions: Different glycaemic profiles with different metabolic traits and different degrees of subsequent glycaemic deterioration can be identified using data from a frequently sampled mixed-meal tolerance test in individuals with T2D. Subgroups with the highest peaks had greater metabolic risk.

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U2 - 10.1371/journal.pone.0242360

DO - 10.1371/journal.pone.0242360

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C2 - 33253307

AN - SCOPUS:85097034291

SN - 1932-6203

VL - 15

JO - PLoS ONE

JF - PLoS ONE

IS - 11

M1 - e0242360

ER -

Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes: An IMI-DIRECT study

Abstract

ASJC Scopus subject areas

UN SDGs

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

Cite this

Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes: An IMI-DIRECT study

Abstract

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)

Cite this