ABSTRACT: Preclinical models of type 1 diabetes mellitus exhibit marked declines in skeletal muscle health including significant impairments in muscle repair. The present study investigated, for the first time, whether muscle repair was altered in young adults with uncomplicated type 1 diabetes (T1D) following damaging exercise.In this cohort study, eighteen physically-active young adults (M=22.1, SEM=0.9 years) with T1D (n, male/female=4/5; MHbA1c= 58, SEMHbA1c=5.9 mmol/mol) and without T1D (n, male/female=4/5) performed 300 unilateral eccentric contractions (90°s-1) of the knee extensors. Prior to exercise, at 48-hours and at 96-hours after exercise, participants gave a venous blood sample and vastus lateralis biopsy and performed a maximal voluntary isometric knee extension. Skeletal muscle extracellular matrix content, and satellite cell content/proliferation were assessed by immunofluorescence. Transmission electron microscopy was used to quantify ultrastructural damage.Maximal isometric strength was comparable between T1D and their sex-matched control group prior to exercise for both sexes. Immediately following damaging exercise, strength was decreased in both groups but there was a moderate effect size for lower strength during recovery in the T1D group at both 48-hours and 96-hours. Serum creatine kinase, an indicator of muscle damage, was moderately higher in T1D participants compared to controls at rest, and exhibited a small elevation 96-hours after exercise. Immunofluorescence analyses showed satellite cell content was lower at all timepoints in those with type 1 diabetes. T1D participants demonstrated a moderate delay in satellite cell proliferation (as assessed by Pax7+/Ki67+ nuclei counts) after exercise, reaching peak levels of proliferation 48-hours after control participants. Despite these differences, those with T1D did not exhibit greater ultrastructural muscle damage than controls as assessed by electron microscopy. Finally, a transcriptomic investigation of T1D muscle revealed several networks of dysregulated genes involving RNA translation as well as mitochondrial respiration function, providing potential explanations for previous observations of mitochondrial dysfunction in similar T1D cohorts. Our novel findings indicate that skeletal muscle from physically active, young adults with moderately controlled T1D may have a reduced ability to handle, and repair from, damaging exercise. While larger cohort studies are clearly needed, these results suggest that those with T1D may require longer recovery times following damaging exercise.
