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. 2021 Oct;64(10):2322-2333.
doi: 10.1007/s00125-021-05535-y. Epub 2021 Aug 17.

Twenty-four hour assessments of substrate oxidation reveal differences in metabolic flexibility in type 2 diabetes that are improved with aerobic training

Elvis A Carnero  1 , Christopher P Bock  1 , Giovanna Distefano  1 , Karen D Corbin  1 , Natalie A Stephens  1 , Richard E Pratley  1 , Steven R Smith  1 , Bret H Goodpaster  1 , Lauren M Sparks  2
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Twenty-four hour assessments of substrate oxidation reveal differences in metabolic flexibility in type 2 diabetes that are improved with aerobic training

Elvis A Carnero et al. Diabetologia. 2021 Oct.

Abstract

Aims/hypothesis: The aim of this study was to assess metabolic flexibility (MetFlex) in participants with type 2 diabetes within the physiologically relevant conditions of sleeping, the post-absorptive (fasting) state and during meals using 24 h whole-room indirect calorimetry (WRIC) and to determine the impact of aerobic training on these novel features of MetFlex.

Methods: Normal-weight, active healthy individuals (active; n = 9), obese individuals without type 2 diabetes (ND; n = 9) and obese individuals with type 2 diabetes (n = 23) completed baseline metabolic assessments. The type 2 diabetes group underwent a 10 week supervised aerobic training intervention and repeated the metabolic assessments. MetFlex was assessed by indirect calorimetry in response to insulin infusion and during a 24 h period in a whole-room indirect calorimeter. Indices of MetFlex evaluated by WRIC included mean RQ and RQ kinetic responses after ingesting a standard high-carbohydrate breakfast (RQBF) and sleep RQ (RQsleep). Muscle mitochondrial energetics were assessed in the vastus lateralis muscle in vivo and ex vivo using 31P-magnetic resonance spectroscopy and high-resolution respirometry, respectively.

Results: The three groups had significantly different RQsleep values (active 0.823 ± 0.04, ND 0.860 ± 0.01, type 2 diabetes 0.842 ± 0.03; p < 0.05). The active group had significantly faster RQBF and more stable RQsleep responses than the ND and type 2 diabetes groups, as demonstrated by steeper and flatter slopes, respectively. Following the training intervention, the type 2 diabetes group displayed significantly increased RQBF slope. Several indices of RQ kinetics had significant associations with in vivo and ex vivo muscle mitochondrial capacities.

Conclusions/interpretation: Twenty-four hour WRIC revealed that physiological RQ responses exemplify differences in MetFlex across a spectrum of metabolic health and correlated with skeletal muscle mitochondrial energetics. Defects in certain features of MetFlex were improved with aerobic training, emphasising the need to assess multiple aspects of MetFlex and disentangle insulin resistance from MetFlex in type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT01911104.

Funding: This study was funded by the ADA (grant no. 7-13-JF-53).

Keywords: Clamp; Exercise intervention; Meal challenge; Metabolic flexibility; Mitochondrial capacity; Whole-room indirect calorimetry.

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