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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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2020 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 63, no 4, p. 744-756Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Springer Nature , 2020. Vol. 63, no 4, p. 744-756
Keywords [en]
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
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:kth:diva-277260DOI: 10.1007/s00125-019-05083-6ISI: 000510285900001PubMedID: 32002573Scopus ID: 2-s2.0-85078864179OAI: oai:DiVA.org:kth-277260DiVA, id: diva2:1447739
Note

QC 20200626

Correction in: Diabetologia, Volume 64, Issue 1, Pages 260 - 261, January 2021. DOI: 10.1007/s00125-020-05311-4, ISI: 000589133900001, ScopusID: s2.0-85095953342, PubMedID: 33184701

Available from: 2020-06-26 Created: 2020-06-26 Last updated: 2022-09-28Bibliographically approved

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Schwenk, Jochen M.

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