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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\u00a0h plasma glucose levels after an oral glucose load.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a Greenlandic population cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092655), 2\u00a0h plasma glucose levels were obtained after an OGTT, physical activity was estimated as physical activity energy expenditure and\n                      <jats:italic>TBC1D4<\/jats:italic>\n                      genotype was determined. We performed\n                      <jats:italic>TBC1D4<\/jats:italic>\n                      \u2013physical activity interaction analysis, applying a linear mixed model to correct for genetic admixture and relatedness.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Physical activity was inversely associated with 2\u00a0h plasma glucose levels (\u03b2[main effect of physical activity] \u22120.0033 [mmol\/l] \/ [kJ\u00a0kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00a0day\n                      <jats:sup>\u22121<\/jats:sup>\n                      ],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20096.5\u2009\u00d7\u200910\n                      <jats:sup>\u22125<\/jats:sup>\n                      ), and significantly more so among homozygous carriers of the\n                      <jats:italic>TBC1D4<\/jats:italic>\n                      risk variant compared with heterozygous carriers and non-carriers (\u03b2[interaction] \u22120.015 [mmol\/l] \/ [kJ\u00a0kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00a0day\n                      <jats:sup>\u22121<\/jats:sup>\n                      ],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0085). The estimated effect size suggests that 1\u00a0h of vigorous physical activity per day (compared with resting) reduces 2\u00a0h plasma glucose levels by an additional ~0.7\u00a0mmol\/l in homozygous carriers of the risk variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>\n                      Physical activity improves glucose homeostasis particularly in homozygous\n                      <jats:italic>TBC1D4<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data repository<\/jats:title>\n                    <jats:p>\n                      The Greenlandic Cardio-Metabochip data for the Inuit Health in Transition study has been deposited at the European Genome-phenome Archive (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.ebi.ac.uk\/ega\/dacs\/EGAC00001000736\">https:\/\/www.ebi.ac.uk\/ega\/dacs\/EGAC00001000736<\/jats:ext-link>\n                      ) under accession EGAD00010001428.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-021-05461-z","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T21:05:17Z","timestamp":1619643917000},"page":"1795-1804","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers"],"prefix":"10.1007","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6573-4959","authenticated-orcid":false,"given":"Theresia M.","family":"Schnurr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil","family":"J\u00f8rsboe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Chadt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inger K.","family":"Dahl-Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas M.","family":"Kristensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f8rgen F. 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