Impaired Function and Altered Morphology in the Skeletal Muscles of Adult Men and Women with Type 1 Diabetes

Abstract

Context: Previous investigations on skeletal muscle health in type 1 diabetes (T1D) have generally focused on later stages of disease progression where comorbidities are present and are posited as a primary mechanism of muscle dysfunction. Objective: To investigate skeletal muscle function and morphology across the adult lifespan in those with and without T1D. Design: Participants underwent maximal contraction (MVC) testing, resting muscle biopsy, and venous blood sampling. Setting: Procedures in this study were undertaken at the McMaster University Medical Centre. Participants: Sixty-five healthy adult (18-78 years old) men/males and women/females (T1D=34; control=31) matched for age/biological sex/body mass index; self-reported physical activity levels were included. Main Outcome Measures: Our primary measure in this study was MVC, with supporting histological/immunofluorescent measures. Results: After 35 years of age ("older adults"), MVC declined quicker in T1D subjects compared to controls. Loss of strength in T1D was accompanied by morphological changes associated with accelerated aging. Type 1 myofiber grouping was higher in T1D, and the groups were larger and more numerous than in controls. Older T1D females exhibited more myofibers expressing multiple myosin heavy chain isoforms (hybrid fibers) than controls, another feature of accelerated aging. Conversely, T1D males exhibited a shift toward type 2 fibers, with less evidence of myofiber grouping or hybrid fibers. Conclusions: These data suggest impairments to skeletal muscle function and morphology exist in T1D. The decline in strength with T1D is accelerated after 35 years of age and may be responsible for the earlier onset of frailty, which characterizes those with diabetes.