There is strong evidence that skeletal muscle health is compromised in persons with type 1 diabetes mellitus (T1D). These impairments include reduced strength, mitochondrial dysfunction, and decreased satellite cell (SC) content. Maintaining healthy muscle requires successful muscle repair. Preclinical models of T1D consistently show impaired muscle regeneration. To date, the impact of T1D on human skeletal muscle repair has not been established; however, attenuated repair would account for the reduced functional capacity and premature institutionalization that often characterizes those with diabetes. The purpose of this study was to determine the impact of T1D on the recovery of skeletal muscle function, morphology, and ultrastructure after 300 unilateral eccentric contractions (90°/s) of the knee extensors. Eighteen men and women (18-30 years old) with (n=9) and without (n=9) T1D performed the exercise protocol. Pre-damage, and at 48- and 96-hours post-damage, subjects gave a blood sample and vastus lateralis biopsy, and performed a maximal isometric knee extension. Given the sex-specific differences in muscle damage, control and T1D men and women were analyzed together and separately. Force production and recovery were comparable between control and T1D men and women. Exercise-related increases in creatine kinase activity and ultrastructural damage were also comparable between groups. There was a trend towards T1D men having more type 2 fast-twitch muscle fibers than T1D women (p=0.055). While baseline SC content was not different between groups, proliferating SC content was trending lower at 48-, and higher at 96-hours post-damage in T1D women compared to controls (p=0.07). In those with T1D, there was no correlation between muscle damage and HbA1c, but HbA1c was strongly correlated with vigorous physical activity (r=0.881, p=0.002). Contrary to preclinical studies, our data is the first to show that skeletal muscle repair is largely unaltered in otherwise healthy young adults with T1D. We attribute these differences to glycemic control and speculate that muscle repair is unaffected if individuals are optimally managing their diabetes. Considering the exercise-related dysglycemia seen in T1D, our results emphasize a need to define the dose of physical activity required for those with diabetes to properly regulate their blood glucose levels. We expect that this would in turn, improve skeletal muscle health and ultimately, extend the healthy lifespan of those living with T1D. / Thesis / Master of Science in Medical Sciences (MSMS) / Type 1 diabetes mellitus (T1D) is a chronic disease where the body does not make enough insulin to control blood glucose levels. Overtime, unstable blood glucose levels can damage major organ systems, including skeletal muscle. Skeletal muscle plays a pivotal role in regulating our physical and metabolic capacities. In those with T1D, exercise-mediated improvements in muscle health have been shown to delay health complications. However, we do not know how diabetic skeletal muscle repairs from exercise in humans. In this thesis, we investigated the ability of skeletal muscle to recover from damaging exercise in young adults with T1D. For the first time, we showed that skeletal muscle repair was similar between otherwise healthy young adults with T1D and those without diabetes. Our findings suggest that persons with T1D can engage in high levels of physical activity without compromising their muscle health. Further studies are needed to understand how exercise type, intensity, and duration impact glycemic control in men and women with T1D.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/25506 |
| Date | January 2020 |
| Creators | Grafham, Grace K. |
| Contributors | Hawke, Thomas J., Medical Sciences (Cell Biology and Metabolism) |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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