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@article{Koivula:2020:10.1007/s00125-019-05083-6,
author = {Koivula, RW and Atabaki-Pasdar, N and Giordano, GN and White, T and Adamski, J and Bell, JD and Beulens, J and Brage, S and Brunak, S and De, Masi F and Dermitzakis, ET and Forgie, IM and Frost, G and Hansen, T and Hansen, TH and Hattersley, A and Kokkola, T and Kurbasic, A and Laakso, M and Mari, A and McDonald, TJ and Pedersen, O and Rutters, F and Schwenk, JM and Teare, HJA and Thomas, EL and Vinuela, A and Mahajan, A and McCarthy, MI and Ruetten, H and Walker, M and Pearson, E and Pavo, I and Franks, PW},
doi = {10.1007/s00125-019-05083-6},
journal = {Diabetologia},
pages = {744--756},
title = {The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study},
url = {http://dx.doi.org/10.1007/s00125-019-05083-6},
volume = {63},
year = {2020}
}

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TY  - JOUR
AB  - Aims/hypothesisIt 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).MethodsWe 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.ResultsThe 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 wi
AU  - Koivula,RW
AU  - Atabaki-Pasdar,N
AU  - Giordano,GN
AU  - White,T
AU  - Adamski,J
AU  - Bell,JD
AU  - Beulens,J
AU  - Brage,S
AU  - Brunak,S
AU  - De,Masi F
AU  - Dermitzakis,ET
AU  - Forgie,IM
AU  - Frost,G
AU  - Hansen,T
AU  - Hansen,TH
AU  - Hattersley,A
AU  - Kokkola,T
AU  - Kurbasic,A
AU  - Laakso,M
AU  - Mari,A
AU  - McDonald,TJ
AU  - Pedersen,O
AU  - Rutters,F
AU  - Schwenk,JM
AU  - Teare,HJA
AU  - Thomas,EL
AU  - Vinuela,A
AU  - Mahajan,A
AU  - McCarthy,MI
AU  - Ruetten,H
AU  - Walker,M
AU  - Pearson,E
AU  - Pavo,I
AU  - Franks,PW
DO  - 10.1007/s00125-019-05083-6
EP  - 756
PY  - 2020///
SN  - 0012-186X
SP  - 744
TI  - The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study
T2  - Diabetologia
UR  - http://dx.doi.org/10.1007/s00125-019-05083-6
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000510285900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://link.springer.com/article/10.1007%2Fs00125-019-05083-6
UR  - http://hdl.handle.net/10044/1/80082
VL  - 63
ER  -

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