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

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Schnurr, TM, Jørsboe, E, Chadt, A, Dahl-Petersen, IK, Kristensen, JM, Wojtaszewski, JFP, 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, bind 64, nr. 8, s. 1795-1804. 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. F. P., 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, 64(8), 1795-1804. https://doi.org/10.1007/s00125-021-05461-z

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MLA

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Author

Schnurr, Theresia M ; Jørsboe, Emil ; Chadt, Alexandra ; Dahl-Petersen, Inger K ; Kristensen, Jonas M ; Wojtaszewski, Jørgen F P ; Springer, Christian ; Bjerregaard, Peter ; Brage, Søren ; Pedersen, Oluf ; Moltke, Ida ; Grarup, Niels ; Al-Hasani, Hadi ; Albrechtsen, Anders ; Jørgensen, Marit E ; Hansen, Torben. / Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers. I: Diabetologia. 2021 ; Bind 64, Nr. 8. s. 1795-1804.

Bibtex

@article{e80e69520f7e46c780008b6ca4686d6c,
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 = "Arctic, Gene-environment interaction, Lifestyle therapy, Physical activity, Postprandial hyperglycaemia, TBC1D4 loss-of-function",
author = "Schnurr, {Theresia M} and Emil J{\o}rsboe and Alexandra Chadt and Dahl-Petersen, {Inger K} and Kristensen, {Jonas M} and Wojtaszewski, {J{\o}rgen F P} 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 E} and Torben Hansen",
year = "2021",
month = aug,
doi = "10.1007/s00125-021-05461-z",
language = "English",
volume = "64",
pages = "1795--1804",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer",
number = "8",

}

RIS

TY - JOUR

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

AU - Schnurr, Theresia M

AU - Jørsboe, Emil

AU - Chadt, Alexandra

AU - Dahl-Petersen, Inger K

AU - Kristensen, Jonas M

AU - Wojtaszewski, Jørgen F P

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 E

AU - Hansen, Torben

PY - 2021/8

Y1 - 2021/8

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 - Arctic

KW - Gene-environment interaction

KW - Lifestyle therapy

KW - Physical activity

KW - Postprandial hyperglycaemia

KW - TBC1D4 loss-of-function

UR - http://www.scopus.com/inward/record.url?scp=85105400323&partnerID=8YFLogxK

U2 - 10.1007/s00125-021-05461-z

DO - 10.1007/s00125-021-05461-z

M3 - Journal article

C2 - 33912980

VL - 64

SP - 1795

EP - 1804

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 8

ER -

ID: 67902065