ALTERED MYOFIBER FUNCTION AND PHYSIOLOGY IN TYPE 1 DIABETES

Abstract

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.