Translational Research Institute, AdventHealth, Orlando, FL, USA.
Diabetologia. 2021 Oct;64(10):2322-2333. doi: 10.1007/s00125-021-05535-y. Epub 2021 Aug 17.
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.
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) and sleep RQ (RQ). Muscle mitochondrial energetics were assessed in the vastus lateralis muscle in vivo and ex vivo using P-magnetic resonance spectroscopy and high-resolution respirometry, respectively.
The three groups had significantly different RQ 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 and more stable RQ 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 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.
ClinicalTrials.gov NCT01911104.
This study was funded by the ADA (grant no. 7-13-JF-53).
目的/假设：本研究旨在使用 24 小时整体间接测热法（WRIC）评估 2 型糖尿病患者在睡眠、吸收后（禁食）状态和进餐期间的代谢灵活性（MetFlex），并确定有氧运动训练对 MetFlex 这些新特征的影响。
正常体重、活跃的健康个体（活跃组；n=9）、无 2 型糖尿病的肥胖个体（ND 组；n=9）和肥胖的 2 型糖尿病个体（n=23）完成了基线代谢评估。2 型糖尿病组接受了 10 周的监督有氧运动干预，并重复了代谢评估。通过间接测热法评估 MetFlex 对胰岛素输注的反应以及在 24 小时整体间接测热仪中的反应。WRIC 评估的 MetFlex 指数包括摄入标准高碳水化合物早餐后平均 RQ 和 RQ 动力学反应（RQ）和睡眠 RQ（RQ）。使用 P 磁共振波谱和高分辨率呼吸测量法分别在活体和离体的股外侧肌中评估肌肉线粒体能量学。
三组的 RQ 值有显著差异（活跃组 0.823±0.04，ND 组 0.860±0.01，2 型糖尿病组 0.842±0.03；p<0.05）。与 ND 和 2 型糖尿病组相比，活跃组的 RQ 响应更快，更稳定，表现为斜率更陡和平坦。经过训练干预后，2 型糖尿病组的 RQ 斜率显著增加。RQ 动力学的几个指数与活体和离体肌肉线粒体容量有显著相关性。
结论/解释：24 小时 WRIC 显示，生理 RQ 反应体现了代谢健康谱中不同的 MetFlex，并与骨骼肌线粒体能量学相关。有氧运动训练改善了 MetFlex 的某些特征，强调需要评估 MetFlex 的多个方面，并在 2 型糖尿病中区分胰岛素抵抗和 MetFlex。
ClinicalTrials.gov NCT01911104。
本研究由 ADA（7-13-JF-53 号）资助。
