The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study
dc.contributor.author | Koivula, RW | |
dc.contributor.author | Atabaki-Pasdar, N | |
dc.contributor.author | Giordano, GN | |
dc.contributor.author | White, T | |
dc.contributor.author | Adamski, J | |
dc.contributor.author | Bell, JD | |
dc.contributor.author | Beulens, J | |
dc.contributor.author | Brage, S | |
dc.contributor.author | Brunak, S | |
dc.contributor.author | De Masi, F | |
dc.contributor.author | Dermitzakis, ET | |
dc.contributor.author | Forgie, IM | |
dc.contributor.author | Frost, G | |
dc.contributor.author | Hansen, T | |
dc.contributor.author | Hansen, TH | |
dc.contributor.author | Hattersley, A | |
dc.contributor.author | Kokkola, T | |
dc.contributor.author | Kurbasic, A | |
dc.contributor.author | Laakso, M | |
dc.contributor.author | Mari, A | |
dc.contributor.author | McDonald, TJ | |
dc.contributor.author | Pedersen, O | |
dc.contributor.author | Rutters, F | |
dc.contributor.author | Schwenk, JM | |
dc.contributor.author | Teare, HJA | |
dc.contributor.author | Thomas, EL | |
dc.contributor.author | Vinuela, A | |
dc.contributor.author | Mahajan, A | |
dc.contributor.author | McCarthy, MI | |
dc.contributor.author | Ruetten, H | |
dc.contributor.author | Walker, M | |
dc.contributor.author | Pearson, E | |
dc.contributor.author | Pavo, I | |
dc.contributor.author | Franks, PW | |
dc.date.accessioned | 2020-05-14T07:42:12Z | |
dc.date.issued | 2020-01-30 | |
dc.description.abstract | Aims/hypothesis: It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435). Methods: We defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively. Results: The TC and TC-PA models showed better fit than null models (TC: χ2 = 242, p = 0.004 and χ2 = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: χ2 = 180, p = 0.041 and χ2 = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity with glycaemic control was primarily mediated by variables in the liver fat cycle. Conclusions/interpretation: These analyses partially support the mechanisms proposed in the twin-cycle model and highlight mechanistic pathways through which insulin sensitivity and liver fat mediate the association between physical activity and glycaemic control. | en_GB |
dc.description.sponsorship | European Union Horizon 2020 | en_GB |
dc.description.sponsorship | European Federation of Pharmaceutical Industries and Associations (EFPIA) | en_GB |
dc.description.sponsorship | Novo Nordisk Foundation | en_GB |
dc.description.sponsorship | MedImmune | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.identifier.citation | Vol. 63, pp. 744 - 756 | en_GB |
dc.identifier.doi | 10.1007/s00125-019-05083-6 | |
dc.identifier.grantnumber | 115317 | en_GB |
dc.identifier.grantnumber | NNF18OC0031650 | en_GB |
dc.identifier.grantnumber | MC_UU_12015/3 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/121038 | |
dc.language.iso | en | en_GB |
dc.publisher | Springer Verlag | en_GB |
dc.rights | © The Author(s) 2020. 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/. | en_GB |
dc.subject | Beta cell function | en_GB |
dc.subject | Ectopic fat | en_GB |
dc.subject | Glycaemic control | en_GB |
dc.subject | Insulin sensitivity | en_GB |
dc.subject | Physical activity | en_GB |
dc.subject | Prediabetes | en_GB |
dc.subject | Structural equation modelling | en_GB |
dc.subject | Type 2 diabetes | en_GB |
dc.title | The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-05-14T07:42:12Z | |
dc.identifier.issn | 0012-186X | |
dc.description | This is the final version. Available on open access from Springer Verlag via the DOI in this record | en_GB |
dc.description | Data availability: Requests for access to IMI DIRECT data, including data presented here, can made to DIRECTdataaccess@Dundee.ac.uk. | en_GB |
dc.identifier.journal | Diabetologia | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2019-11-29 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2020-01-30 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-05-14T07:37:22Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2020-05-14T07:42:25Z | |
refterms.panel | A | en_GB |
refterms.depositException | publishedGoldOA |
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