Project 453039

Type 1 Diabetes (T1D) results when the body destroys the insulin-producing beta cells of the pancreas. While insulin injections are essential for managing T1D, they are not a cure and do not prevent the devastating complications (including kidney failure, vascular disease) which can shorten the lifespan of those with T1D by as much as 15 years. T1D complications result from an inability to control blood glucose (dysglycemia), blood lipids (dyslipidemia) and insulin resistance. Strategies for preventing T1D complications are urgently needed and would have a profound impact on the quality of life and lifespan of more than 300,000 T1D people in Canada. Current T1D therapy injects insulin subcutaneously; delivering insulin directly to the periphery and skipping the first pass through the liver. Skeletal muscle, the largest insulin-sensitive organ in the periphery, now becomes the principal tissue for blood glucose management and the major site for metabolism of fats. Despite the importance of skeletal muscle in regulating the three primary variables leading to T1D complications, you may be surprised to learn that our understanding of the impact of T1D on human skeletal muscle at the cellular and molecular level is virtually zero. This lack of mechanistic understanding may explain the extreme variability in exercise benefits for those with T1D. We propose to undertake a comprehensive analysis of skeletal muscle health (function, metabolism and microvasculature) in younger and older T1D adults. We will then determine which facets of muscle health are improved with an exercise intervention, and how a sedentary period affects these improvements. We will also determine whether these effects are observed equally in both males and females. Our preliminary evidence supports our hypothesis that T1D negatively impacts skeletal muscle function and metabolism, and that T1D exercise requirements may need to exceed that of individuals without T1D to achieve the same benefits.