Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers

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Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers. / Schnurr, Theresia Maria; Jørsboe, Emil; Chadt, Alexandra; Dahl-Petersen, Inger Katrine; Kristensen, Jonas Møller; Wojtaszewski, Jørgen; Springer, Christian; Bjerregaard, Peter; Brage, Søren; Pedersen, Oluf; Moltke, Ida; Grarup, Niels; Al-Hasani, Hadi; Albrechtsen, Anders; Jørgensen, Marit Eika; Hansen, Torben.

In: Diabetologia, 29.04.2021.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Schnurr, TM, Jørsboe, E, Chadt, A, Dahl-Petersen, IK, Kristensen, JM, Wojtaszewski, J, Springer, C, Bjerregaard, P, Brage, S, Pedersen, O, Moltke, I, Grarup, N, Al-Hasani, H, Albrechtsen, A, Jørgensen, ME & Hansen, T 2021, 'Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers', Diabetologia. https://doi.org/10.1007/s00125-021-05461-z

APA

Schnurr, T. M., Jørsboe, E., Chadt, A., Dahl-Petersen, I. K., Kristensen, J. M., Wojtaszewski, J., Springer, C., Bjerregaard, P., Brage, S., Pedersen, O., Moltke, I., Grarup, N., Al-Hasani, H., Albrechtsen, A., Jørgensen, M. E., & Hansen, T. (2021). Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers. Diabetologia. https://doi.org/10.1007/s00125-021-05461-z

Vancouver

Schnurr TM, Jørsboe E, Chadt A, Dahl-Petersen IK, Kristensen JM, Wojtaszewski J et al. Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers. Diabetologia. 2021 Apr 29. https://doi.org/10.1007/s00125-021-05461-z

Author

Schnurr, Theresia Maria ; Jørsboe, Emil ; Chadt, Alexandra ; Dahl-Petersen, Inger Katrine ; Kristensen, Jonas Møller ; Wojtaszewski, Jørgen ; Springer, Christian ; Bjerregaard, Peter ; Brage, Søren ; Pedersen, Oluf ; Moltke, Ida ; Grarup, Niels ; Al-Hasani, Hadi ; Albrechtsen, Anders ; Jørgensen, Marit Eika ; Hansen, Torben. / Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers. In: Diabetologia. 2021.

Bibtex

@article{833242bdba88451da206967b726572e6,
title = "Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers",
abstract = "Aims/hypothesis: The common muscle-specific TBC1D4 p.Arg684Ter loss-of-function variant defines a subtype of non-autoimmune diabetes in Arctic populations. Homozygous carriers are characterised by elevated postprandial glucose and insulin levels. Because 3.8% of the Greenlandic population are homozygous carriers, it is important to explore possibilities for precision medicine. We aimed to investigate whether physical activity attenuates the effect of this variant on 2 h plasma glucose levels after an oral glucose load.Methods: In a Greenlandic population cohort (n = 2655), 2 h plasma glucose levels were obtained after an OGTT, physical activity was estimated as physical activity energy expenditure and TBC1D4 genotype was determined. We performed TBC1D4-physical activity interaction analysis, applying a linear mixed model to correct for genetic admixture and relatedness.Results: Physical activity was inversely associated with 2 h plasma glucose levels (β[main effect of physical activity] -0.0033 [mmol/l] / [kJ kg-1 day-1], p = 6.5 × 10-5), and significantly more so among homozygous carriers of the TBC1D4 risk variant compared with heterozygous carriers and non-carriers (β[interaction] -0.015 [mmol/l] / [kJ kg-1 day-1], p = 0.0085). The estimated effect size suggests that 1 h of vigorous physical activity per day (compared with resting) reduces 2 h plasma glucose levels by an additional ~0.7 mmol/l in homozygous carriers of the risk variant.Conclusions/interpretation: Physical activity improves glucose homeostasis particularly in homozygous TBC1D4 risk variant carriers via a skeletal muscle TBC1 domain family member 4-independent pathway. This provides a rationale to implement physical activity as lifestyle precision medicine in Arctic populations.Data repository: The Greenlandic Cardio-Metabochip data for the Inuit Health in Transition study has been deposited at the European Genome-phenome Archive ( https://www.ebi.ac.uk/ega/dacs/EGAC00001000736 ) under accession EGAD00010001428.",
keywords = "Faculty of Science, Arctic, Gene-environment interaction, Lifestyle therapy, Physical activity, Postprandial hyperglycaemia, TBC1D4, Loss-of-function",
author = "Schnurr, {Theresia Maria} and Emil J{\o}rsboe and Alexandra Chadt and Dahl-Petersen, {Inger Katrine} and Kristensen, {Jonas M{\o}ller} and J{\o}rgen Wojtaszewski and Christian Springer and Peter Bjerregaard and S{\o}ren Brage and Oluf Pedersen and Ida Moltke and Niels Grarup and Hadi Al-Hasani and Anders Albrechtsen and J{\o}rgensen, {Marit Eika} and Torben Hansen",
note = "CURIS 2021 NEXS 156 (Open Access --> upload pdf-fil)",
year = "2021",
month = apr,
day = "29",
doi = "10.1007/s00125-021-05461-z",
language = "English",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer",

}

RIS

TY - JOUR

T1 - Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers

AU - Schnurr, Theresia Maria

AU - Jørsboe, Emil

AU - Chadt, Alexandra

AU - Dahl-Petersen, Inger Katrine

AU - Kristensen, Jonas Møller

AU - Wojtaszewski, Jørgen

AU - Springer, Christian

AU - Bjerregaard, Peter

AU - Brage, Søren

AU - Pedersen, Oluf

AU - Moltke, Ida

AU - Grarup, Niels

AU - Al-Hasani, Hadi

AU - Albrechtsen, Anders

AU - Jørgensen, Marit Eika

AU - Hansen, Torben

N1 - CURIS 2021 NEXS 156 (Open Access --> upload pdf-fil)

PY - 2021/4/29

Y1 - 2021/4/29

N2 - Aims/hypothesis: The common muscle-specific TBC1D4 p.Arg684Ter loss-of-function variant defines a subtype of non-autoimmune diabetes in Arctic populations. Homozygous carriers are characterised by elevated postprandial glucose and insulin levels. Because 3.8% of the Greenlandic population are homozygous carriers, it is important to explore possibilities for precision medicine. We aimed to investigate whether physical activity attenuates the effect of this variant on 2 h plasma glucose levels after an oral glucose load.Methods: In a Greenlandic population cohort (n = 2655), 2 h plasma glucose levels were obtained after an OGTT, physical activity was estimated as physical activity energy expenditure and TBC1D4 genotype was determined. We performed TBC1D4-physical activity interaction analysis, applying a linear mixed model to correct for genetic admixture and relatedness.Results: Physical activity was inversely associated with 2 h plasma glucose levels (β[main effect of physical activity] -0.0033 [mmol/l] / [kJ kg-1 day-1], p = 6.5 × 10-5), and significantly more so among homozygous carriers of the TBC1D4 risk variant compared with heterozygous carriers and non-carriers (β[interaction] -0.015 [mmol/l] / [kJ kg-1 day-1], p = 0.0085). The estimated effect size suggests that 1 h of vigorous physical activity per day (compared with resting) reduces 2 h plasma glucose levels by an additional ~0.7 mmol/l in homozygous carriers of the risk variant.Conclusions/interpretation: Physical activity improves glucose homeostasis particularly in homozygous TBC1D4 risk variant carriers via a skeletal muscle TBC1 domain family member 4-independent pathway. This provides a rationale to implement physical activity as lifestyle precision medicine in Arctic populations.Data repository: The Greenlandic Cardio-Metabochip data for the Inuit Health in Transition study has been deposited at the European Genome-phenome Archive ( https://www.ebi.ac.uk/ega/dacs/EGAC00001000736 ) under accession EGAD00010001428.

AB - Aims/hypothesis: The common muscle-specific TBC1D4 p.Arg684Ter loss-of-function variant defines a subtype of non-autoimmune diabetes in Arctic populations. Homozygous carriers are characterised by elevated postprandial glucose and insulin levels. Because 3.8% of the Greenlandic population are homozygous carriers, it is important to explore possibilities for precision medicine. We aimed to investigate whether physical activity attenuates the effect of this variant on 2 h plasma glucose levels after an oral glucose load.Methods: In a Greenlandic population cohort (n = 2655), 2 h plasma glucose levels were obtained after an OGTT, physical activity was estimated as physical activity energy expenditure and TBC1D4 genotype was determined. We performed TBC1D4-physical activity interaction analysis, applying a linear mixed model to correct for genetic admixture and relatedness.Results: Physical activity was inversely associated with 2 h plasma glucose levels (β[main effect of physical activity] -0.0033 [mmol/l] / [kJ kg-1 day-1], p = 6.5 × 10-5), and significantly more so among homozygous carriers of the TBC1D4 risk variant compared with heterozygous carriers and non-carriers (β[interaction] -0.015 [mmol/l] / [kJ kg-1 day-1], p = 0.0085). The estimated effect size suggests that 1 h of vigorous physical activity per day (compared with resting) reduces 2 h plasma glucose levels by an additional ~0.7 mmol/l in homozygous carriers of the risk variant.Conclusions/interpretation: Physical activity improves glucose homeostasis particularly in homozygous TBC1D4 risk variant carriers via a skeletal muscle TBC1 domain family member 4-independent pathway. This provides a rationale to implement physical activity as lifestyle precision medicine in Arctic populations.Data repository: The Greenlandic Cardio-Metabochip data for the Inuit Health in Transition study has been deposited at the European Genome-phenome Archive ( https://www.ebi.ac.uk/ega/dacs/EGAC00001000736 ) under accession EGAD00010001428.

KW - Faculty of Science

KW - Arctic

KW - Gene-environment interaction

KW - Lifestyle therapy

KW - Physical activity

KW - Postprandial hyperglycaemia

KW - TBC1D4

KW - Loss-of-function

U2 - 10.1007/s00125-021-05461-z

DO - 10.1007/s00125-021-05461-z

M3 - Journal article

C2 - 33912980

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

ER -

ID: 260994635