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 |
---|---|
Main Authors: | , , , , , , , , , , , , , , , |
Format: | Text |
Language: | English |
Published: |
Springer Berlin Heidelberg
2021
|
Subjects: | |
Online Access: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245392/ http://www.ncbi.nlm.nih.gov/pubmed/33912980 https://doi.org/10.1007/s00125-021-05461-z |
id |
ftpubmed:oai:pubmedcentral.nih.gov:8245392 |
---|---|
record_format |
openpolar |
spelling |
ftpubmed:oai:pubmedcentral.nih.gov:8245392 2023-05-15T15:00:30+02:00 Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers 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 2021-04-29 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245392/ http://www.ncbi.nlm.nih.gov/pubmed/33912980 https://doi.org/10.1007/s00125-021-05461-z en eng Springer Berlin Heidelberg http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245392/ http://www.ncbi.nlm.nih.gov/pubmed/33912980 http://dx.doi.org/10.1007/s00125-021-05461-z © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . CC-BY Diabetologia Article Text 2021 ftpubmed https://doi.org/10.1007/s00125-021-05461-z 2021-07-18T00:23:54Z 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. GRAPHICAL ABSTRACT: ... Text Arctic greenlandic inuit PubMed Central (PMC) Arctic Diabetologia 64 8 1795 1804 |
institution |
Open Polar |
collection |
PubMed Central (PMC) |
op_collection_id |
ftpubmed |
language |
English |
topic |
Article |
spellingShingle |
Article 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 |
topic_facet |
Article |
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. GRAPHICAL ABSTRACT: ... |
format |
Text |
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 |
author_facet |
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 |
author_sort |
Schnurr, Theresia M. |
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 |
publisher |
Springer Berlin Heidelberg |
publishDate |
2021 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245392/ http://www.ncbi.nlm.nih.gov/pubmed/33912980 https://doi.org/10.1007/s00125-021-05461-z |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic greenlandic inuit |
genre_facet |
Arctic greenlandic inuit |
op_source |
Diabetologia |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245392/ http://www.ncbi.nlm.nih.gov/pubmed/33912980 http://dx.doi.org/10.1007/s00125-021-05461-z |
op_rights |
© The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
op_rightsnorm |
CC-BY |
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 |
_version_ |
1766332602085539840 |