Oxygen Delivery and Utilization During Acute Dynamic Exercise


Background and aims Polycystic ovary syndrome (PCOS) and type 1 diabetes are relatively common endocrinopathies, often manifesting across most of the lifespan. Cardiovascular risk is increased in both PCOS and type 1 diabetes, affecting patients' quality of life and overall prognosis. Acute dynamic exercise is a widely used tool to examine an individual’s cardiovascular health. Particularly, peak pulmonary O 2 uptake (V̇ O 2peak ), measured during maximal incremental dynamic exercise and reflecting the highest achievable level of whole-body oxidative metabolism, is a strong and independent predictor of cardiovascular morbidity and mortality. This is because V̇ O 2 response to exercise consists of integrated serial steps of systemic O 2 delivery (i.e., pulmonary function, cardiac pump function, blood O 2 carrying capacity), peripheral O 2 delivery (i.e., skeletal muscle blood flow), and peripheral O 2 extraction and utilization (i.e., muscle O 2 diffusion and metabolism). Early identification of potential disease-related derangements in these integrated organ systems would provide important information on clinical manifestations of PCOS and type 1 diabetes; however, studies examining the issue from the integrated perspective have been sparse. Little evidence also exists on effects of long-term exercise training on the signs of the derangements related to type 1 diabetes. The aim of this thesis was to study O 2 delivery and utilization during acute dynamic exercise in both healthy individuals and individuals with PCOS or type 1 diabetes. The adaptations induced by long-term exercise training were also examined in individuals with type 1 diabetes and compared with those in healthy individuals. Acute exercise was thus used as a physiological probe to identify early signs of cardiovascular dysfunction related to the disease states of PCOS and type 1 diabetes, whereas exercise training was employed to demonstrate whether it alleviates such early signs associated with type 1 diabetes. Subjects and methods Studies I-IV of this thesis belonged to a Canadian-Finnish research collaboration entitled “ARTEMIS – Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection of Discovery, Prevention and Knowledge Exchange”. Data on 22 healthy adult men (Study I), 15 adult overweight or obese women with and 15 without PCOS (Study II), seven adult men with and 10 without type 1 diabetes (Study III), and eight adult men with and eight without type 1 diabetes (Study IV) were included in the final analyses. The groups of Studies II-IV were matched for age, anthropometry, and leisure-time physical activity (II, III) or baseline V̇ O 2peak (IV). Neither PCOS women (II) nor men with type 1 diabetes (III, IV) had clinically overt cardiovascular disease. The subjects performed either maximal incremental treadmill (I) or cycling (II-IV) exercise tests, and in Study IV the subjects did so both before and after a 1-year individualized exercise training intervention. Integrated data were collected during the exercise tests; alveolar gas exchange (volume turbine and mass spectrometry) (I-IV), arterial O 2 saturation (pulse oximetry) (I-IV), heart rate (electrocardiography) (I-IV), 12 cardiac pump function (PhysioFlow impedance cardiography) (II, III), and active leg muscle deoxygenation (I, III, IV) and blood flow (III) (near-infrared spectroscopy [NIRS]), were monitored. In Study I, less active arm muscle and cerebral deoxygenation were also monitored (NIRS). In Study IV, peak O 2 pulse was calculated to indirectly reflect cardiac pump function. Total hemoglobin mass (I) and blood volume (III) were also determined (carbon monoxide rebreathing method), and blood samples were drawn particularly to measure hemoglobin concentration (I-IV) and to evaluate glycemic control (glycosylated hemoglobin A 1c ) (III, IV). Results I: Deoxygenation profiles, reflecting local imbalance between O 2 delivery and utilization, in the tissues of interest were linked to alveolar gas exchange (i.e., whole- body) responses during maximal incremental treadmill exercise in healthy men. II: Reduced V̇ O 2peak , reduced peak systemic O 2 extraction, and a pronounced cardiac response to increasing V̇ O 2 but otherwise intact systemic O 2 delivery were observed in overweight and obese PCOS women. III: Reduced peak cardiac pump function, being associated with reduced blood volume, and independently deteriorated peak active leg muscle blood flow led to reduced V̇ O 2peak and were suggested to be associated with glycosylated hemoglobin A 1c in men with type 1 diabetes. IV: The 1-year training intervention improved V̇ O 2peak and peak O 2 pulse similarly in men with and without type 1 diabetes but had no effect on NIRS-derived local active muscle O 2 extraction or glycosylated hemoglobin A 1c in men with type 1 diabetes. In addition, consistent associations between training dose and responses were observed in healthy men but not in those with type 1 diabetes. Conclusions The findings of this thesis overall highlight the integrated nature of O 2 delivery and utilization responses to acute dynamic exercise. The following conclusions on disease- related early signs of cardiovascular dysfunction can be drawn: In women with excess weight, PCOS per se is linked to alterations in peripheral adjustments to acute dynamic exercise rather than to limitations of systemic O 2 delivery. In type 1 diabetes, both systemic and peripheral cardiovascular impairments, being affected by glycemic control, limit O 2 delivery during acute dynamic exercise. Furthermore, regular exercise training improves V̇ O 2peak and probably cardiac pump function, and hence, improves the overall prognosis of cardiovascular morbidity in type 1 diabetes. However, exercise training, at least to the extent in Study IV, is not able to alleviate diabetes-related defects within active muscle microvasculature or to improve patients' glycemic control. The lack of dose-response associations in men with type 1 diabetes may highlight the need for more individualized exercise regimens in individuals with type 1 diabetes. These conclusions lead future multi-disciplinary research to identify more detailed mechanisms behind, the clinical significance of, and treatment for the observed disease-specific early signs of cardiovascular dysfunction.