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The role of physica...
The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes : an IMI DIRECT study
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- Koivula, Robert W. (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital,University of Oxford
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- Atabaki-Pasdar, Naeimeh (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Giordano, Giuseppe N. (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- White, T. (author)
- University of Cambridge
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- Adamski, J. (author)
- National University of Singapore,Technical University of Munich,Helmholtz Zentrum München,University of Oxford
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- Bell, J. D. (author)
- University of Westminster
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- Beulens, J. (author)
- Academic Medical Center of University of Amsterdam (AMC)
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- Brage, S. (author)
- University of Southern Denmark
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- Brunak, S. (author)
- University of Copenhagen,Technical University of Denmark
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- De Masi, F. (author)
- Technical University of Denmark,University of Copenhagen
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- Dermitzakis, E. T. (author)
- University of Geneva Medical School,University of Geneva,Swiss Institute for Bioinformatics (SIB)
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- Forgie, I. M. (author)
- Ninewells Hospital and Medical School
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- Frost, G. (author)
- Imperial College London
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- Hansen, T. (author)
- University of Southern Denmark,University of Copenhagen
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Hansen, T. H. (author)
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- Hattersley, A. (author)
- University of Exeter
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- Kokkola, T. (author)
- University of Eastern Finland
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- Kurbasic, Azra (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Laakso, M. (author)
- University of Eastern Finland
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- Mari, A. (author)
- CNR Istituto per le Tecnologie Applicate ai Beni Culturali (CNR-ITABC)
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- McDonald, T. J. (author)
- University of Exeter
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- Pedersen, O. (author)
- University of Copenhagen
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- Rutters, F. (author)
- Sanofi-Aventis Deutschland GmbH
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- Schwenk, Jochen M. (author)
- KTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik
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Teare, H. J. A. (author)
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- Thomas, E. L. (author)
- University of Westminster
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- Vinuela, A. (author)
- Swiss Institute for Bioinformatics (SIB),University of Geneva Medical School,University of Geneva
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- Mahajan, A. (author)
- Wellcome Trust Centre for Human Genetics
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- McCarthy, M. I. (author)
- Churchill Hospital,Wellcome Trust Centre for Human Genetics,Genentech, Inc,University of Oxford
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- Ruetten, H. (author)
- Sanofi-Aventis Deutschland GmbH
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- Walker, M. (author)
- University of Newcastle upon Tyne
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- Pearson, E. (author)
- Ninewells Hospital and Medical School
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- Pavo, I. (author)
- Eli Lilly and Company
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- Franks, Paul W. (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital,Harvard T.H. Chan School of Public Health,Norrland University Hospital,University of Oxford
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Consortium, for the IMI DIRECT (author)
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(creator_code:org_t)
- 2020-01-30
- 2020
- English.
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In: Diabetologia. - : Springer Nature. - 0012-186X .- 1432-0428. ; 63:4, s. 744-756
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Beta cell function
- Ectopic fat
- Glycaemic control
- Insulin sensitivity
- Physical activity
- Prediabetes
- Structural equation modelling
- Type 2 diabetes
- carbohydrate
- fat
- glucose
- hemoglobin A1c
- protein
- abdominal fat
- accelerometry
- adult
- Article
- body fat distribution
- cohort analysis
- female
- glucose blood level
- glucose homeostasis
- glycemic control
- human
- major clinical study
- male
- non insulin dependent diabetes mellitus
- nuclear magnetic resonance imaging
- oral glucose tolerance test
- priority journal
- Beta cell function
- Ectopic fat
- Glycaemic control
- Insulin sensitivity
- Physical activity
- Prediabetes
- Structural equation modelling
- Type 2 diabetes
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Koivula, Robert ...
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Atabaki-Pasdar, ...
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Giordano, Giusep ...
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White, T.
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Adamski, J.
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Bell, J. D.
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show more...
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Beulens, J.
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Brage, S.
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Brunak, S.
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De Masi, F.
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Dermitzakis, E. ...
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Forgie, I. M.
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Frost, G.
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Hansen, T.
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Hansen, T. H.
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Hattersley, A.
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Kokkola, T.
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Kurbasic, Azra
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Laakso, M.
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Mari, A.
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McDonald, T. J.
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Pedersen, O.
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Rutters, F.
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Schwenk, Jochen ...
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Teare, H. J. A.
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Thomas, E. L.
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Vinuela, A.
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Mahajan, A.
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McCarthy, M. I.
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Ruetten, H.
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Walker, M.
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Pearson, E.
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Pavo, I.
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Franks, Paul W.
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Consortium, for ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Microbiology in ...
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Diabetologia
- By the university
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Royal Institute of Technology
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Lund University