The objective of this thesis was to examine muscle function and myofiber physiology in skeletal muscles in those with type 1 diabetes (T1D) by investigating the effects of diabetic myopathy on these metrics of muscle health under various conditions: at rest, after exercise and with increasing age. These works recruited adults from surrounding communities with T1D and non-diabetic counterparts (i.e. controls) matched for age, sex, body mass index, and self-reported physical activity levels. We hypothesized that adults with T1D would exhibit decreased muscle function (i.e. lower maximal strength) and altered myofiber physiology in each of these conditions. At rest, we observed that those with T1D exhibited more fast-twitch fibers and fewer satellite cells. After exercise, T1D muscles recovered less strength, showed higher amounts of myofiber damage, and delayed satellite cell proliferation. With increasing age, adults with T1D exhibited exaggerated signs of muscular aging compared to age-matched controls in the form of more abundant hybrid fibers and type 1 fiber grouping. Finally, individuals with T1D exhibited higher baseline expression of myostatin, a negative muscle growth regulator, compared to controls. Overall, our work provides the first evidence in muscle dysfunction from humans with T1D at various ages and after damaging exercise. Our findings provide novel insights on muscle health and its contribution to overall health during this lifelong, debilitating disease. Our work aims to guide future clinical & exercise guidelines with the ultimate purpose of improving the lives of millions of individuals living with T1D. / Thesis / Doctor of Philosophy (PhD) / Type 1 diabetes (T1D) is a disease that affects millions of adults worldwide by harming their ability to manage blood sugar levels. Insulin therapy has allowed for longer and healthier lives but requires constant attention manage blood sugar levels. Over time, the quality of life declines because of complications from T1D. Muscle is able to control blood sugar levels through exercise, but little is known about muscle in those with T1D. Therefore, the purpose of this work was to examine skeletal muscle health in people with T1D who do not have other complications. We found that adults with T1D exhibit signs of aging in their muscles earlier than non-diabetic people. Also, we observed that muscle from young adults with T1D recovered slower from exercise. Finally, we learned that people with T1D have more of a muscle-shrinking protein. This is the first evidence of dysfunctional muscle fibers at rest, after exercise, and with age in adults with T1D. This work aims to improve future guidelines for millions of adults with T1D.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/27234 |
| Date | January 2021 |
| Creators | Dial, Athan |
| Contributors | Hawke, Thomas, Medical Sciences |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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