The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study
Year: 2020
Type: article
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: = 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.
Source: Diabetologia
Authors: Robert W. Koivula, Naeimeh Atabaki-Pasdar, Giuseppe N. Giordano, Tom White, Jerzy Adamski, Jimmy D. Bell, Joline Beulens, Søren Brage, Søren Brunak, Federico De Masi, Emmanouil T. Dermitzakis, Ian M. Forgie, Gary Frost, Torben Hansen, Tue H. Hansen, Andrew Hattersley, Tarja Kokkola, Azra Kurbasic, Markku Laakso, Andrea Mari, Timothy J. McDonald, Oluf Pedersen, Femke Rutters, Jochen M. Schwenk, Harriet J. A. Teare, E. Louise Thomas, Ana Vinuela, Anubha Mahajan, Mark I. McCarthy, Hartmut Ruetten, Mark Walker, Ewan Pearson, Imre Pavo, Paul W. Franks
Institutions: Lund University, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Skåne University Hospital, University of Cambridge, MRC Epidemiology Unit, National University of Singapore, Helmholtz Munich, Technical University of Munich, Amsterdam Public Health, Amsterdam University Medical Centers, Amsterdam UMC Location Vrije Universiteit Amsterdam, University of Southern Denmark, University of Copenhagen, Novo Nordisk Foundation, Technical University of Denmark, University of Geneva, SIB Swiss Institute of Bioinformatics, Institute of Genetics and Genomics in Geneva, University of Dundee, Ninewells Hospital, Imperial College London, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Exeter, NIHR Exeter Clinical Research Facility, University of Eastern Finland, Kuopio University Hospital, National Research Council, Science for Life Laboratory, KTH Royal Institute of Technology, Centre for Human Genetics, Genentech, Churchill Hospital, NIHR Oxford Biomedical Research Centre, Sanofi (Germany), Newcastle University, Eli Lilly (United States), Harvard University, University Hospital of Umeå
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,480
Funders: Eli Lilly and Company, Pfizer, AstraZeneca, Sanofi, European Federation of Pharmaceutical Industries and Associations, National Institute for Health and Care Research, European Commission, Lunds Universitet, Novo Nordisk, MedImmune, Novo Nordisk Fonden, Innovative Medicines Initiative, Servier, Medical Research Council
OpenAlex ID: W3004161228