Muscle Morphology and the Insulin Resistance Syndrome : A Population-Based Study of 70 Year-Old-Men in Uppsala

Sammanfattning: Skeletal muscle accounts for the largest part of insulin-mediated glucose uptake. Insulin resistance (IR) is the main component of insulin resistance syndrome (IRS) and is an essential cause of a number of cardiovascular risk factors. This thesis investigates the relationships between muscle morphological characteristics and IRS because skeletal muscle is responsible for the majority of glucose uptake.In this population-based sample of 70-year-old men, higher proportion of type I fibers as well as higher capillarization were related to higher insulin sensitivity and higher self-reported physical activity, which were related to a lower prevalence of type IIB fibers. Serum triglycerides, HDL cholesterol and plasminogen activator inhibitor-1 (PAI-1) activity were significantly related to fiber distribution and muscle capillarization and muscle morphology, in part, explained the association between these metabolic risk factors with physical activity level. BMI, glucose intolerance, PAI-1 activity, serum FFA concentration, proportion of type IIB fibers, HDL cholesterol level, drug treatment, physical activity level, and W/H ratio together explained 55% of the variation in the insulin sensitivity index. In addition, almost a twofold improvement of the correlations was seen after correcting for intraindividual variation. Glucose tolerant hypertensive subjects showed a lower capillary supply when compared to controls. Capillary density was negatively correlated to the increase in mean arterial pressure over two decades as well as to supine heart rate 20 years before. Interestingly, supine heart rate showed an independent inverse association to the percentage of type I fibers and a positive correlation to the percentage of type IIB muscle fibers. Capillary density and elevated serum free fatty (FFA) acid values were inversely associated with insulin-mediated blood flow and thus to endothelial dysfunction, which has been linked to IR. In fact, capillary density and serum FFA level together explained 71% of the variation in insulin-mediated leg blood flow changes.In conclusion, these population-based findings support the observations that muscle morphological features and insulin sensitivity are related to each other. Muscle morphology might explain some of the beneficial impact of physical activity on the components of IRS. Accordingly, we suggest that alterations in muscle morphology should be considered as an essential part of the IRS.