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. 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.