Intermittent hypoxia as a means to improve aerobic capacity in type 2 diabetes

Physical inactivity and a low maximal aerobic capacity (VO_2max) strongly predict morbidity and mortality in patients with type 2 diabetes (T2D). Patients with T2D have a reduced VO_2max when compared with healthy individuals of similar age, weight, and physical activity levels, and this lower aerobic capacity is usually attributed to a reduced oxygen delivery to the working muscles. The oxygen carrying capacity of the blood, as well as increases in cardiac output and blood flow, contribute to the delivery of oxygen to the active muscles during exercise. Hemoglobin mass (Hb mass), a key determinant of oxygen carrying capacity, is suggested to be reduced in patients with T2D following the observation of a lower blood volume (BV) in combination with normal hematocrit levels in this population. Therefore, a lower Hb mass, in addition to a reported lower BV and impaired cardiovascular response to exercise, likely contributes to the reduced oxygen delivery and VO_2max in patients with T2D. While exercise training increases Hb mass, BV, and consequently VO_2max, the majority of patients with T2D are not physically active, highlighting the need for alternative methods to improve VO_2max in this population. Exposure to hypoxia triggers the release of erythropoietin, the hormone regulating red blood cell production, which increases Hb mass and consequently BV. Exposure to mild intermittent hypoxia (IH), characterized by few and short episodes of hypoxia at a fraction of inspired oxygen ranging between 10 and 14% interspersed with cycles of normoxia, increased red blood cell volume, Hb mass, and plasma volume in patients with coronary artery disease or chronic obstructive pulmonary disease, which resulted in an improved VO_2max in both populations. We hypothesize that 12 exposures to mild IH over a period of 4weeks will increase Hb mass, BV, cardiac function, and VO_2max in patients with T2D. Therefore, exposures to mild IH may increase oxygen delivery and VO_2max without the need to perform exercise in patients with T2D.