Effects of a Single Bout of Interval Hypoxia on Cardiorespiratory Control in Patients With Type 1 Diabetes

Hypoxemia is common in diabetes, and reflex responses to hypoxia are blunted. These abnormalities could lead to cardiovascular/renal complications. Interval hypoxia (IH) (5–6 short periods of hypoxia each day over 1–3 weeks) was successfully used to improve the adaptation to hypoxia in patients with chronic obstructive pulmonary disease. We tested whether IH over 1 day could initiate a long-lasting response potentially leading to better adaptation to hypoxia. In 15 patients with type 1 diabetes, we measured hypoxic and hypercapnic ventilatory responses (HCVRs), ventilatory recruitment threshold (VRT-CO₂), baroreflex sensitivity (BRS), blood pressure, and blood lactate before and after 0, 3, and 6 h of a 1-h single bout of IH. All measurements were repeated on a placebo day (single-blind protocol, randomized sequence). After IH (immediately and after 3 h), hypoxic and HCVR increased, whereas the VRT-CO₂ dropped. No such changes were observed on the placebo day. Systolic and diastolic blood pressure increased, whereas blood lactate decreased after IH. Despite exposure to hypoxia, BRS remained unchanged. Repeated exposures to hypoxia over 1 day induced an initial adaptation to hypoxia, with improvement in respiratory reflexes. Prolonging the exposure to IH (>2 weeks) in type 1 diabetic patients will be a matter for further studies.Diabetes is closely related to impaired function of the autonomic nervous system (ANS). As a consequence, autonomic dysfunction can worsen the prognosis of the disease and result in serious complications (1,2).Assuming that ANS abnormalities such as sympathetic overactivity or reduced cardiorespiratory reflexes might at an early stage be attributed to a functional origin (as they can be favorably influenced by simple functional maneuvers) rather than organic lesions (3), they could possibly be reversible by an appropriate intervention. In diabetic patients, low oxygen content (hypoxemia) is common in most organ and tissues (4–8). Hypoxia in the blood or tissues is known to induce sympathetic activation, hence, altering cardiovascular reflex tests regardless of neural damage (9,10).Interval hypoxia (IH) could be a useful strategy to improve hypoxia, since IH has largely been implemented in the adaptation to high altitude (11,12). Due to the improved adaptation to hypoxia, IH also improves exercise performance in athletes (13) and improves ANS function in various diseases (14,15). IH consists of repeated short periods of hypoxia (5–6 min) interspersed by equal periods of normoxia, thus creating a sort of stress that in turn evokes a counterregulatory response by altering the preexisting homeostasis. If adequately administered, sufficient repetitions lead to a persisting supercompensatory (“training”) effect (16,17) and improved response to hypoxia. The use of IH in patients with chronic bronchitis (18) increased ventilation, oxygen saturation, and chemoreflex activity; reduced hypoxia-dependent sympathetic overactivity; and right shifted the lactate-load curve during exercise as an effect of improved aerobic metabolism (19). IH also modifies the number of circulating immune cells, due to the links between ANS, immune system, and hypoxia (20).In patients with diabetes, abnormal activity of respiratory reflexes (21–26) and reduced responses to hypoxia are frequently observed (27,28), and the immune defense is depressed (29). Altogether, these considerations suggest that IH could induce favorable results in diabetes.However, as IH has never been applied in patients with type 1 diabetes before, we tested whether a single short bout of IH could elicit favorable changes that improve the hypoxia and the respiratory reflexes and could lead to improved ANS function. In addition, since the responses to hypoxia are multidimensional, we tested its initial effects on the immune system and on the aerobic/anaerobic metabolism at rest by monitoring the lactate production after IH. Finally, we assessed the possible effects of IH on lipid peroxidation and formation of malondialdehyde (MDA), which are markers for cell damage and oxidative stress, respectively, and are generally used when the effects of hypoxia interventions are to be evaluated (30).The aim of this study was to examine the chain of events occurring after one single bout of IH in patients with type 1 diabetes. For this purpose, we examined cardiorespiratory, metabolic, and hematological responses before and at different times after 1 h of IH and followed the changes over the rest of the same day (6 h).