Mechanisms of Fatigability in People with Type 2 Diabetes and Prediabetes
Abstract
Dynamic fatiguing exercise of limb muscles is the basis of exercise training and a cornerstone of management of type 2 diabetes mellitus (T2D) and prediabetes. Little is known however, about the fatigability of limb muscles (the acute exercise induced reduction in force or power) and the involved mechanisms in people with T2D and prediabetes. Current evidence suggests that people with T2D have reduced muscle strength and power, are more fatigable after static contractions, and have physical impairments affecting activities of daily living. However, impaired function in people with T2D compared with controls is larger for dynamic than static tasks. The purpose of this dissertation was to determine the magnitude and mechanisms of fatigability in people with T2D and prediabetes after a dynamic exercise task with the knee extensor muscles. Importantly, these studies matched people with T2D and prediabetes to controls based on age, sex, physical activity and body size. The first studies determined the magnitude of fatigability and the neural and muscular mechanisms in people with T2D and controls (Study 1) and in prediabetes (Study 2). People with T2D had approximately twice the decline in both power (fatigability) and electrically-evoked muscle contractile properties than controls after the six-minute dynamic task with the knee extensor muscles. People with prediabetes also had greater fatigability (~50%) and reductions in contractile properties than controls, but less than people with T2D. The reduction in voluntary activation (neural drive to the muscle) after fatiguing exercise was not different between people with T2D, prediabetes and controls. Thus, the greater fatigability in people with T2D was due to mechanisms within the skeletal muscle rather than neural drive. Study 3 determined whether skeletal muscle blood flow could explain the greater fatigability in people with T2D. People with T2D had greater fatigability and lower blood flow after exercise than controls, and there was an association between fatigability and the exercise-induced increase in muscle blood flow after exercise. Collectively, these data suggest that people with T2D and prediabetes have greater fatigability during dynamic exercise with knee extensor muscles due to mechanisms effecting muscle contractile properties, including impaired skeletal muscle blood flow.