The Oxygen Transport Cascade During Maximal-Intensity Exercise in Uncomplicated Type 1 Diabetes: A Narrative Review

Exercise capacity can be impaired in individuals with type 1 diabetes (T1D), even before the development of diabetes-related complications. Yet some individuals with T1D achieve exercise capacities high enough to compete in endurance disciplines at a professional level. Exercise capacity, most often assessed by maximal oxygen uptake ( $\dot{V}$ O_2max), is constrained by the physiological systems that ensure oxygen transfer from the atmosphere to the working muscle. The aim of this review was therefore to identify which of these systems are adversely affected by T1D, with a particular focus on the cardiovascular function and muscle oxidative capacity. Reduced cardiac output and stroke volume appear to be consistent contributors to reduced $\dot{V}$ O_2max in T1D, with decreased blood volume likely playing a contributory role through impaired ventricular preload. Although growing evidence indicates that mitochondrial dysfunction can occur in T1D and is associated with increased oxidative stress, its contribution to reduced $\dot{V}$ O_2max remains uncertain. Importantly, available evidence suggests that limitations are distributed across multiple steps of the O₂ transport cascade, from cardiac function and blood volume to muscle perfusion and oxidative capacity, rather than attributable to a single dominant factor. These limitations are not systematic across individuals with T1D and appear more closely related to glycemic control, as assessed by HbA_1c, than to disease duration per se. Insulin resistance, which can occur independently of obesity in T1D, is also emerging as a potential contributor to impaired oxygen transport and utilization during exercise. Improved understanding of these mechanisms and their interactions may help optimize T1D management and preserve exercise capacity.