Hansen Maria, Lange Kristine Kjær, Stausholm Martin Bjørn, Dela Flemming
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Physical and Occupational Therapy, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Endocrinol Diabetes Metab. 2025 May;8(3):e70044. doi: 10.1002/edm2.70044.
Type 2 diabetes (T2D) is characterised by insulin resistance and possibly by impaired metabolic flexibility, the latter referring to the body's ability to switch between fuel sources. This review systematically examines metabolic flexibility, measured by changes in the respiratory exchange ratio (ΔRER) during hyperinsulinaemic clamps, across lean, overweight/obese, and T2D populations.
A comprehensive search of PubMed identified 65 studies meeting the inclusion criteria, with 35 using a ~40 mU/m/min insulin infusion rate for accurate comparisons. These studies included 985 participants: 256 lean, 497 overweight/obese, and 232 T2D individuals. The differences in ΔRER between the three groups were meta-analysed.
Basal RER values did not significantly differ across groups, but insulin-stimulated ΔRER was higher in lean individuals compared to overweight/obese and T2D groups (ΔRER values 0.10, 0.07 and 0.07, respectively; p = 0.037) indicating greater metabolic flexibility in the lean group. However, high statistical heterogeneity in the ΔRER within-group results (I values: 92.3%-94.5%) suggests considerable variability among studies. A meta-regression analysis accounting for age, sex, and BMI indicated that only BMI was significantly associated with ΔRER. Factors contributing to the remaining heterogeneity likely include differences in participant characteristics (e.g., glycaemic control) and study design.
The review highlights the need for standardised data presentation in metabolic studies. Overall, metabolic flexibility appears more influenced by overweight status than T2D per se, challenging the notion of a distinct metabolic inflexibility threshold for T2D.
2型糖尿病（T2D）的特征是胰岛素抵抗，可能还伴有代谢灵活性受损，后者指身体在不同燃料来源之间切换的能力。本综述系统地研究了通过高胰岛素钳夹期间呼吸交换率变化（ΔRER）来衡量的代谢灵活性，涉及瘦人群体、超重/肥胖人群和T2D人群。
对PubMed进行全面检索，确定了65项符合纳入标准的研究，其中35项使用约40 mU/m/min的胰岛素输注速率以进行准确比较。这些研究包括985名参与者：256名瘦人、497名超重/肥胖者和232名T2D患者。对三组之间的ΔRER差异进行荟萃分析。
各组间基础RER值无显著差异，但与超重/肥胖组和T2D组相比，瘦人组胰岛素刺激后的ΔRER更高（ΔRER值分别为0.10、0.07和0.07；p = 0.037），表明瘦人组具有更大的代谢灵活性。然而，组内ΔRER结果存在较高的统计学异质性（I值：92.3%-94.5%），表明各研究之间存在相当大的变异性。一项考虑年龄、性别和BMI的荟萃回归分析表明，只有BMI与ΔRER显著相关。导致其余异质性的因素可能包括参与者特征（如血糖控制）和研究设计的差异。
该综述强调了代谢研究中标准化数据呈现的必要性。总体而言，代谢灵活性似乎更多地受到超重状态的影响，而非T2D本身，这对T2D存在独特代谢不灵活性阈值的观点提出了挑战。
