Alterations in skeletal muscle repair in young adults with type 1 diabetes mellitus.

Abstract

Though preclinical models of type 1 diabetes (T1D) exhibit impaired muscle regeneration, this has yet to be investigated in humans with T1D. Here, we investigated the impact of damaging exercise (eccentric quadriceps contractions) in 18 physically active young adults with and without T1D. Pre- and postexercise (48 h and 96 h), the participants provided blood samples, vastus lateralis biopsies, and performed maximal voluntary quadriceps contractions (MVCs). Skeletal muscle sarcolemmal integrity, extracellular matrix (ECM) content, and satellite cell (SC) content/proliferation were assessed by immunofluorescence. Transmission electron microscopy was used to quantify ultrastructural damage. MVC was comparable between T1D and controls before exercise. Postexercise, MVC was decreased in both groups, but subjects with T1D exhibited moderately lower strength recovery at both 48 h and 96 h. Serum creatine kinase, an indicator of muscle damage, was moderately higher in participants with T1D at rest and exhibited a small elevation 96 h postexercise. Participants with T1D showed lower SC content at all timepoints and demonstrated a moderate delay in SC proliferation after exercise. A greater number of myofibers exhibited sarcolemmal damage (disrupted dystrophin) and increased ECM (laminin) content in participants with T1D despite no differences between groups in ultrastructural damage as assessed by electron microscopy. Finally, transcriptomic analyses revealed dysregulated gene networks involving RNA translation and mitochondrial respiration, providing potential explanations for previous observations of mitochondrial dysfunction in similar cohorts with T1D. Our findings indicate that skeletal muscle in young adults with moderately controlled T1D is altered after damaging exercise, suggesting that longer recovery times following intense exercise may be necessary.