Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers
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 homozy...
Published in: | Diabetologia |
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Main Authors: | , , , , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
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2021
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Online Access: | https://curis.ku.dk/portal/da/publications/physical-activity-attenuates-postprandial-hyperglycaemia-in-homozygous-tbc1d4-lossoffunction-mutation-carriers(833242bd-ba88-451d-a206-967b726572e6).html https://doi.org/10.1007/s00125-021-05461-z https://curis.ku.dk/ws/files/276700232/Schnurr2021_Article_PhysicalActivityAttenuatesPost.pdf |
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ftcopenhagenunip:oai:pure.atira.dk:publications/833242bd-ba88-451d-a206-967b726572e6 2024-05-19T07:35:37+00:00 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 2021 application/pdf https://curis.ku.dk/portal/da/publications/physical-activity-attenuates-postprandial-hyperglycaemia-in-homozygous-tbc1d4-lossoffunction-mutation-carriers(833242bd-ba88-451d-a206-967b726572e6).html https://doi.org/10.1007/s00125-021-05461-z https://curis.ku.dk/ws/files/276700232/Schnurr2021_Article_PhysicalActivityAttenuatesPost.pdf eng eng info:eu-repo/semantics/openAccess 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 , vol. 64 , pp. 1795-1804 . https://doi.org/10.1007/s00125-021-05461-z /dk/atira/pure/core/keywords/TheFacultyOfScience Faculty of Science Arctic Gene-environment interaction Lifestyle therapy Physical activity Postprandial hyperglycaemia TBC1D4 Loss-of-function article 2021 ftcopenhagenunip https://doi.org/10.1007/s00125-021-05461-z 2024-05-02T00:33:13Z 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. Article in Journal/Newspaper Arctic greenlandic inuit University of Copenhagen: Research Diabetologia 64 8 1795 1804 |
institution |
Open Polar |
collection |
University of Copenhagen: Research |
op_collection_id |
ftcopenhagenunip |
language |
English |
topic |
/dk/atira/pure/core/keywords/TheFacultyOfScience Faculty of Science Arctic Gene-environment interaction Lifestyle therapy Physical activity Postprandial hyperglycaemia TBC1D4 Loss-of-function |
spellingShingle |
/dk/atira/pure/core/keywords/TheFacultyOfScience Faculty of Science Arctic Gene-environment interaction Lifestyle therapy Physical activity Postprandial hyperglycaemia TBC1D4 Loss-of-function 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 |
topic_facet |
/dk/atira/pure/core/keywords/TheFacultyOfScience Faculty of Science Arctic Gene-environment interaction Lifestyle therapy Physical activity Postprandial hyperglycaemia TBC1D4 Loss-of-function |
description |
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. |
format |
Article in Journal/Newspaper |
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 |
author_facet |
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 |
author_sort |
Schnurr, Theresia Maria |
title |
Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers |
title_short |
Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers |
title_full |
Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers |
title_fullStr |
Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers |
title_full_unstemmed |
Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers |
title_sort |
physical activity attenuates postprandial hyperglycaemia in homozygous tbc1d4 loss-of-function mutation carriers |
publishDate |
2021 |
url |
https://curis.ku.dk/portal/da/publications/physical-activity-attenuates-postprandial-hyperglycaemia-in-homozygous-tbc1d4-lossoffunction-mutation-carriers(833242bd-ba88-451d-a206-967b726572e6).html https://doi.org/10.1007/s00125-021-05461-z https://curis.ku.dk/ws/files/276700232/Schnurr2021_Article_PhysicalActivityAttenuatesPost.pdf |
genre |
Arctic greenlandic inuit |
genre_facet |
Arctic greenlandic inuit |
op_source |
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 , vol. 64 , pp. 1795-1804 . https://doi.org/10.1007/s00125-021-05461-z |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1007/s00125-021-05461-z |
container_title |
Diabetologia |
container_volume |
64 |
container_issue |
8 |
container_start_page |
1795 |
op_container_end_page |
1804 |
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1799474419512377344 |