Prediabetes Associates With Musculoskeletal Alterations Independent of Total Body Adiposity

BACKGROUND: Excess adiposity is a major risk factor for insulin resistance, prediabetes, and Type 2 diabetes and increases the risk for sarcopenia and osteosarcopenia later in life. It has been proposed that altered metabolic function and musculoskeletal status in people with obesity are directly linked, presumably because they share common pathophysiological mechanisms. However, the effect of metabolic dysfunction, independent of adiposity, on musculoskeletal status is unknown. METHODS: We performed a comprehensive assessment of musculoskeletal status in people with overweight/obesity and prediabetes (n = 12; 72% women; age: 67 ± 6 years; weight: 81 ± 11 kg; mean ± SD) and a control group of sex-, age- and adiposity-matched participants with normoglycaemia (n = 18; 67% women; age: 65 ± 6 years; weight: 81 ± 12 kg). RESULTS: Appendicular muscle mass expressed relative to the sarcopenia threshold (-5.6% ± 2.5% vs. 1.8% ± 2.0%; mean ± SEM) and the bone mineral density T-score (-0.22 ± 0.41 vs. 0.82 ± 0.33) were lower (p < 0.05) in the prediabetic group than the control group. Additionally, the prediabetic group had ~25% smaller (by cross-sectional area) myofibres and ~40% fewer muscle Type 2 macrophages (all p < 0.05), whereas intramyocellular lipid content was more than 50% higher (p < 0.05) in the prediabetic than the control group. Maximal muscle strength was not different between the two groups, but muscle strength during repeated maximum voluntary contractions declined more (p < 0.05) in the prediabetic group. CONCLUSION: In people with overweight/obesity, metabolic dysfunction associates with musculoskeletal dysfunction independent of adiposity.