Literature DB >> 34402932

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

Elvis A Carnero1, Christopher P Bock1, Giovanna Distefano1, Karen D Corbin1, Natalie A Stephens1, Richard E Pratley1, Steven R Smith1, Bret H Goodpaster1, Lauren M Sparks2.   

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).
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Entities:  

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

Mesh:

Year:  2021        PMID: 34402932     DOI: 10.1007/s00125-021-05535-y

Source DB:  PubMed          Journal:  Diabetologia        ISSN: 0012-186X            Impact factor:   10.122


  21 in total

Review 1.  Metabolic Flexibility in Health and Disease.

Authors:  Bret H Goodpaster; Lauren M Sparks
Journal:  Cell Metab       Date:  2017-05-02       Impact factor: 27.287

Review 2.  Fuel selection in human skeletal muscle in insulin resistance: a reexamination.

Authors:  D E Kelley; L J Mandarino
Journal:  Diabetes       Date:  2000-05       Impact factor: 9.461

3.  Five-day comparison of the doubly labeled water method with respiratory gas exchange.

Authors:  D A Schoeller; P Webb
Journal:  Am J Clin Nutr       Date:  1984-07       Impact factor: 7.045

4.  Skeletal muscle mitochondria in insulin resistance: differences in intermyofibrillar versus subsarcolemmal subpopulations and relationship to metabolic flexibility.

Authors:  Peter Chomentowski; Paul M Coen; Zofia Radiková; Bret H Goodpaster; Frederico G S Toledo
Journal:  J Clin Endocrinol Metab       Date:  2010-11-24       Impact factor: 5.958

5.  Family history of diabetes links impaired substrate switching and reduced mitochondrial content in skeletal muscle.

Authors:  Barbara Ukropcova; Olga Sereda; Lilian de Jonge; Iwona Bogacka; Tuong Nguyen; Hui Xie; George A Bray; Steven R Smith
Journal:  Diabetes       Date:  2007-03       Impact factor: 9.461

6.  Restoration of muscle mitochondrial function and metabolic flexibility in type 2 diabetes by exercise training is paralleled by increased myocellular fat storage and improved insulin sensitivity.

Authors:  Ruth C R Meex; Vera B Schrauwen-Hinderling; Esther Moonen-Kornips; Gert Schaart; Marco Mensink; Esther Phielix; Tineke van de Weijer; Jean-Pierre Sels; Patrick Schrauwen; Matthijs K C Hesselink
Journal:  Diabetes       Date:  2009-12-22       Impact factor: 9.461

7.  Relationships between mitochondrial function and metabolic flexibility in type 2 diabetes mellitus.

Authors:  Tineke van de Weijer; Lauren Marie Sparks; Esther Phielix; Ruth Carla Meex; Noud Antonius van Herpen; Matthijs Karel C Hesselink; Patrick Schrauwen; Vera Bettina Schrauwen-Hinderling
Journal:  PLoS One       Date:  2013-02-13       Impact factor: 3.240

8.  Mitochondrial deficiency is associated with insulin resistance.

Authors:  Bret H Goodpaster
Journal:  Diabetes       Date:  2013-04       Impact factor: 9.461

9.  Measuring the short-term substrate utilization response to high-carbohydrate and high-fat meals in the whole-body indirect calorimeter.

Authors:  Andrei Gribok; Jayme L Leger; Michelle Stevens; Reed Hoyt; Mark Buller; William Rumpler
Journal:  Physiol Rep       Date:  2016-06

Review 10.  Room Indirect Calorimetry Operating and Reporting Standards (RICORS 1.0): A Guide to Conducting and Reporting Human Whole-Room Calorimeter Studies.

Authors:  Kong Y Chen; Steve Smith; Eric Ravussin; Jonathan Krakoff; Guy Plasqui; Shigeho Tanaka; Peter Murgatroyd; Robert Brychta; Christopher Bock; Elvis Carnero; Paul Schoffelen; Yoichi Hatamoto; Corey Rynders; Edward L Melanson
Journal:  Obesity (Silver Spring)       Date:  2020-09       Impact factor: 9.298

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