Prediabetes is associated with musculoskeletal dysfunction independent of total body adiposity. Prediabetes is associated with musculoskeletal dysfunction independent of total body adiposity

It has been proposed that there is a direct pathophysiological link between metabolic dysfunction and musculoskeletal degeneration in people with obesity but direct evidence for this proposition is lacking. We performed a comprehensive assessment of musculoskeletal status in people with obesity and prediabetes and a control group of sex-, age- and adiposity-matched participants with normoglycemia. We find muscle mass and bone mineral density scores, muscle growth markers, myofiber size, myofiber capillarization, and muscle type 2 macrophage content are lower, and intramyocellular lipid, but not inter- or intra-muscular adipose tissue, content are higher in people with prediabetes compared with the control group. Moreover, muscle strength during repeated maximum voluntary contractions declines faster in people with prediabetes. These findings demonstrate a close interrelationship between metabolic and musculoskeletal dysfunction in people with obesity and have direct clinical implications, because greater muscle fatigability in people with prediabetes may present a barrier to physical activity. Overall design: We enrolled 30 human subjects (normoglycemic and prediabetic obese) to evaluate putative muscle factors that can affect muscle mass and strength (Cross-sectional study). All participants had muscle biopsies performed and also had functional tests performed to evaluate muscle strength and fatigability. Muscle biopsy samples were then submitted for RNAseq, proteomics, and histology procedures in order to have a comprehensive view of global alterations of muscle proteostasis.

已有研究提出，肥胖人群的代谢功能障碍与肌肉骨骼退变之间存在直接的病理生理学关联，但该假说尚缺乏直接证据支持。本研究对肥胖合并糖尿病前期（prediabetes）人群，以及性别、年龄与体脂均匹配的血糖正常（normoglycemia）对照组人群的肌肉骨骼状态进行了全面评估。
研究结果显示，相较于对照组，糖尿病前期人群的肌肉质量与骨密度评分、肌肉生长标志物、肌纤维横截面积、肌纤维毛细血管密度以及肌肉2型巨噬细胞含量均更低，而肌细胞内脂质含量更高，但肌间及肌内脂肪组织含量无显著差异。此外，糖尿病前期人群在反复最大自主收缩过程中的肌肉力量衰减速度更快。
上述研究结果证实了肥胖人群代谢功能障碍与肌肉骨骼退变之间存在紧密的相互关联，且具有直接的临床指导意义：糖尿病前期人群更高的肌肉易疲劳性可能会成为其参与体力活动的阻碍因素。
研究整体设计：本研究共纳入30名人类受试者（血糖正常的肥胖者与合并糖尿病前期的肥胖者），旨在探究可影响肌肉质量与力量的潜在肌肉因子（横断面研究）。所有受试者均接受了肌肉活检，并完成了评估肌肉力量与易疲劳性的功能测试。随后，我们将肌肉活检样本提交进行RNA测序（RNAseq）、蛋白质组学（proteomics）及组织学（histology）检测，以全面解析肌肉蛋白质稳态（proteostasis）的整体改变情况。