Diabetes mellitus (DM) is a chronic disease that affects almost 24 million people and has large socioeconomic costs. Of these 24 million people, 60-70 % will develop some form of nervous system impairment, including peripheral neuropathy (PN). It is important to understand muscle structure and impairments in people with DM+PN in order to determine appropriate interventions to limit the disability that is associated with DM+PN. The objectives of this research are to describe skeletal muscle structure in people with DM+PN, to determine whether neuropathic muscle structure and composition are associated with movement impairments and functional limitations, and whether neuropathic muscle can be modulated by activity level and/or an exercise intervention.

In Chapter 2, we examine whether intermuscular adipose tissue (IMAT) volumes are different between groups with DM, DM+PN, and a group without DM or PN (NoDMPN). We report that there is no difference in IMAT volumes in these groups, but that increased IMAT is associated with poorer physical performance and the DM+PN group had the lowest measures of physical performance. In Chapter 3, we examine whether activity level in people with DM+PN is associated with IMAT. We report that activity level is inversely associated with IMAT volumes. In Chapter 4, we examine whether an exercise intervention for people with DM+PN is able to improve function and change IMAT and muscle volumes. We report that our duration-based exercise program was successful in increasing 6 minute walk distance, but there was no change in IMAT or muscle volumes. In Chapter 5, we provide a case report detailing an exercise intervention for a specific individual with DM+PN who was able to increase his average activity level and shows improvement in muscle performance and physical function.

Overall, our results suggest that people with DM+PN have lower levels of physical performance than their peers and increased IMAT is associated with poor physical performance. Increased activity levels are associated with decreased IMAT volume. People with DM+PN are able to safely increase their walking distance following an exercise intervention, but we did not see a change in muscle composition. Additional research is needed to determine the specific roles of IMAT in skeletal muscle and function.