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

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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
Diabetologia ( IF 8.4 ) Pub Date : 2021-08-17 , DOI: 10.1007/s00125-021-05535-y
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 ₁

Affiliation

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 (RQ_BF) and sleep RQ (RQ_sleep). 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 RQ_sleep 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 RQ_BF and more stable RQ_sleep 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 RQ_BF 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).

Graphical abstract

中文翻译：

对底物氧化的 24 小时评估揭示了 2 型糖尿病患者代谢灵活性的差异，这些差异通过有氧训练得到改善

目标/假设

本研究的目的是评估 2 型糖尿病参与者在睡眠、吸收后（禁食）状态和用餐期间的生理相关条件下的代谢灵活性（MetFlex），使用 24 小时全房间间接量热法（WRIC）和以确定有氧训练对 MetFlex 的这些新功能的影响。

方法

正常体重、活跃的健康个体（活跃；n = 9）、没有 2 型糖尿病的肥胖个体（ND；n = 9）和患有 2 型糖尿病的肥胖个体（n = 23）完成了基线代谢评估。2 型糖尿病组接受了为期 10 周的有监督有氧训练干预并重复了代谢评估。MetFlex 通过间接量热法对胰岛素输注的反应进行评估，并在 24 小时期间在整个房间的间接量热仪中进行评估。WRIC 评估的 MetFlex 指数包括摄入标准高碳水化合物早餐 (RQ _BF ) 和睡眠 RQ (RQ _sleep）。^{分别使用31} P-磁共振波谱和高分辨率呼吸测量法在体内和离体评估股外侧肌中的肌肉线粒体能量学。

结果

三组的 RQ_睡眠值有显着差异（活跃 0.823 ± 0.04，ND 0.860 ± 0.01，2 型糖尿病 0.842 ± 0.03；p < 0.05）。与 ND 和 2 型糖尿病组相比，活动组的 RQ _BF和更稳定的 RQ_睡眠反应明显更快，分别由更陡峭和更平坦的斜率证明。训练干预后，2 型糖尿病组的 RQ _BF斜率显着增加。RQ 动力学的几个指标与体内和体外肌肉线粒体容量有显着相关性。