The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study.

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 Di... Mehr ...

Verfasser: Koivula, Robert W
Atabaki-Pasdar, Naeimeh
Giordano, Giuseppe N
White, Tom
Adamski, Jerzy
Bell, Jimmy D
Beulens, Joline
Brage, Søren
Brunak, Søren
De Masi, Federico
Dermitzakis, Emmanouil T
Forgie, Ian M
Frost, Gary
Hansen, Torben
Hansen, Tue H
Hattersley, Andrew
Kokkola, Tarja
Kurbasic, Azra
Laakso, Markku
Mari, Andrea
McDonald, Timothy J
Pedersen, Oluf
Rutters, Femke
Schwenk, Jochen M
Teare, Harriet JA
Thomas, E Louise
Vinuela, Ana
Mahajan, Anubha
McCarthy, Mark I
Ruetten, Hartmut
Walker, Mark
Pearson, Ewan
Pavo, Imre
Franks, Paul W
IMI DIRECT Consortium
Dokumenttyp: Artikel
Erscheinungsdatum: 2021
Verlag/Hrsg.: Springer Science and Business Media LLC
Schlagwörter: Beta cell function / Ectopic fat / Glycaemic control / Insulin sensitivity / Physical activity / Prediabetes / Structural equation modelling / Type 2 diabetes / Aged / Blood Glucose / Cohort Studies / Cross-Sectional Studies / Denmark / Diabetes Mellitus / Type 2 / Energy Metabolism / Exercise / Female / Finland / Glucose Tolerance Test / Glycemic Control / Homeostasis / Humans / Insulin Resistance / Male / Middle Aged / Netherlands / Sweden
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29195185
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://www.repository.cam.ac.uk/handle/1810/316865

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 ...