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...

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Bibliographic Details
Main Authors: Schnurr, Theresia M, Jørsboe, Emil, Chadt, Alexandra, Dahl-Petersen, Inger K, Kristensen, Jonas M, Wojtaszewski, Jørgen FP, Springer, Christian, Bjerregaard, Peter, Brage, Søren, Pedersen, Oluf, Moltke, Ida, Grarup, Niels, Al-Hasani, Hadi, Albrechtsen, Anders, Jørgensen, Marit E, Hansen, Torben
Format: Article in Journal/Newspaper
Language:English
Published: Springer Science and Business Media LLC 2021
Subjects:
Arctic
Gene-environment interaction
Lifestyle therapy
Physical activity
Postprandial hyperglycaemia
TBC1D4 loss-of-function
Adult
Blood Glucose
Diabetes Mellitus, Type 2
Exercise
Female
GTPase-Activating Proteins
Gene-Environment Interaction
Genetic Predisposition to Disease
Genotyping Techniques
Glucose Tolerance Test
Greenland
Humans
Hyperglycemia
Insulin
Inuit
Life Style
Loss of Function Mutation
Male
Middle Aged
Postprandial Period
greenlandic
inuit
Online Access:https://dx.doi.org/10.17863/cam.69310
https://www.repository.cam.ac.uk/handle/1810/321851
Description
Summary: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] / ...

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