The association between blood oxygen saturation and baroreflex sensitivity in adults with type 1 diabetes with and without albuminuria.

BACKGROUND: Low baroreflex sensitivity is an indicator of early cardiovascular autonomic neuropathy. We explored the association between baroreflex sensivity and blood oxygen saturation (SpO2) in type 1 diabetes and various degrees of microvascular disease. METHODS: In this Danish-Finnish cross-sectional multicentre study, baroreflex sensivity and SpO2 (pulse oximetry) were examined in persons with type 1 diabetes and normoalbuminuria (n = 98), microalbuminuria (n = 28), or macroalbuminuria (n = 43), and in non-diabetic controls (n = 54). Associations and differences between groups were analysed using regression models and adjustment included age, sex, smoking, HbA1c, blood haemoglobin, urine albumin creatinine ratio, body mass index, and estimated glomerular filtration rate. RESULTS: In type 1 diabetes, higher baroreflex sensitivity was associated with higher SpO2 before adjustment (% increase per one % increase in SpO2 = 20 % (95%CI: 11-30); p < 0.001) and the association remained significant after adjustment (p = 0.02). Baroreflex sensitivity was not different between non-diabetic controls and persons with type 1 diabetes and normoalbuminuria (p = 0.052). Compared with type 1 diabetes and normoalbuminuria, baroreflex sensitivity was lower in micro- (p < 0.001) and macroalbuminuria (p < 0.001). SpO2 was lower in persons with type 1 diabetes and normoalbuminuria compared with non-diabetic controls (p < 0.01). Within the participants with type 1 diabetes, SpO2 was not different in micro- or macroalbuminuria compared with normoalbuminuria (p-values > 0.05), but lower in macro-compared with microalbuminuria (p < 0.01). CONCLUSIONS: Lower baroreflex sensitivity was associated with lower SpO2 in type 1 diabetes. The present study support the hypothesis that hypoxia could be a therapeutic target in persons with type 1 diabetes.

Device-guided slow breathing alters postprandial oxidative stress in young adult males: A randomized sham-controlled crossover trial.

BACKGROUND AND AIMS: Slow, deep breathing (SDB) lowers blood pressure (BP) though the underlying mechanisms are unknown. Redox improvements could facilitate hemodynamic adjustments with SDB though this has not been investigated. The purpose of this randomized, sham-controlled trial was to examine the acute effects of SDB on oxidative stress and endothelial function during a physiological perturbation (high-fat meal) known to induce oxidative stress. METHODS AND RESULTS: Seventeen males (ages 18-35 years) were enrolled, and anthropometric measurements and 7-day physical activity monitoring were completed. Testing sessions consisted of 24-h diet recalls (ASA24), blood sample collection for superoxide dismutase (SOD) and thiobarbituric acid reactive substances (TBARS) analysis, and flow-mediated dilation (FMD). High-fat meals were ingested and 2-min breathing exercises (SDB or sham control breathing) were completed every 15 min during the 4-h postprandial phase. Blood sample collection and FMD were repeated 1-, 2-, and 4-h post meal consumption. Mean body mass index and step counts were 25.6 ± 4.3 kg/m2 and 8165 ± 4405 steps per day, respectively. Systolic and diastolic BP and nutrient intake 24 h prior were similar between conditions. No time or time by condition interaction effects were observed for FMD. The total area under the curve (AUC) for SOD was significantly lower during SDB compared to the sham breathing condition (p < 0.01). No differences were observed in TBARS AUC (p = 0.538). CONCLUSIONS: Findings from the current investigation suggest that SDB alters postprandial redox in the absence of changes in endothelial function in young, healthy males. CLINICAL TRIAL REGISTRATION NUMBER: NCT04864184. CLINICAL TRIALS IDENTIFIER: NCT04864184.

Repression of hypoxia-inducible factor-1 contributes to increased mitochondrial reactive oxygen species production in diabetes.

Background: Excessive production of mitochondrial reactive oxygen species (ROS) is a central mechanism for the development of diabetes complications. Recently, hypoxia has been identified to play an additional pathogenic role in diabetes. In this study, we hypothesized that ROS overproduction was secondary to the impaired responses to hypoxia due to the inhibition of hypoxia-inducible factor-1 (HIF-1) by hyperglycemia. Methods: The ROS levels were analyzed in the blood of healthy subjects and individuals with type 1 diabetes after exposure to hypoxia. The relation between HIF-1, glucose levels, ROS production and its functional consequences were analyzed in renal mIMCD-3 cells and in kidneys of mouse models of diabetes. Results: Exposure to hypoxia increased circulating ROS in subjects with diabetes, but not in subjects without diabetes. High glucose concentrations repressed HIF-1 both in hypoxic cells and in kidneys of animals with diabetes, through a HIF prolyl-hydroxylase (PHD)-dependent mechanism. The impaired HIF-1 signaling contributed to excess production of mitochondrial ROS through increased mitochondrial respiration that was mediated by Pyruvate dehydrogenase kinase 1 (PDK1). The restoration of HIF-1 function attenuated ROS overproduction despite persistent hyperglycemia, and conferred protection against apoptosis and renal injury in diabetes. Conclusions: We conclude that the repression of HIF-1 plays a central role in mitochondrial ROS overproduction in diabetes and is a potential therapeutic target for diabetic complications. These findings are timely since the first PHD inhibitor that can activate HIF-1 has been newly approved for clinical use. Funding: This work was supported by grants from the Swedish Research Council, Stockholm County Research Council, Stockholm Regional Research Foundation, Bert von Kantzows Foundation, Swedish Society of Medicine, Kung Gustaf V:s och Drottning Victorias Frimurarestifelse, Karolinska Institute's Research Foundations, Strategic Research Programme in Diabetes, and Erling-Persson Family Foundation for S-B.C.; grants from the Swedish Research Council and Swedish Heart and Lung Foundation for T.A.S.; and ERC consolidator grant for M.M.

Persons with type 1 diabetes have low blood oxygen levels in the supine and standing body positions.

INTRODUCTION: Blood oxygen saturation is low compared with healthy controls (CONs) in the supine body position in individuals with type 1 diabetes (T1D) and has been associated with complications. Since most of daily life occurs in the upright position, it is of interest if this also applies in the standing body position. In addition, tissue oxygenation in other anatomical sites could show different patterns in T1D. Therefore, we investigated blood, arm and forehead oxygen levels in the supine and standing body positions in individuals with T1D (n=129) and CONs (n=55). RESEARCH DESIGN AND METHODS: Blood oxygen saturation was measured with pulse oximetry. Arm and forehead mixed tissue oxygen levels were measured with near-infrared spectroscopy sensors applied on the skin. RESULTS: Data are presented as least squares means±SEM and differences (95% CIs). Overall blood oxygen saturation was lower in T1D (CON: 97.6%±0.2%; T1D: 97.0%±0.1%; difference: -0.5% (95% CI -0.9% to -0.0%); p=0.034). In all participants, blood oxygen saturation increased after standing up (supine: 97.1%±0.1%; standing: 97.6%±0.2%; difference: +0.6% (95% CI 0.4% to 0.8%); p<0.001). However, the increase was smaller in T1D compared with CON (CON supine: 97.3%±0.2%; CON standing: 98.0%±0.2%; T1D supine: 96.9%±0.2%; T1D standing: 97.2%±0.1%; difference between groups in the change: -0.4% (95% CI -0.6% to -0.2%); p<0.001). Arm oxygen saturation decreased in both groups after standing and more in those with T1D. Forehead oxygen saturation decreased in both groups after standing and there were no differences between the changes when comparing the groups. CONCLUSION: Compared with CON, individuals with T1D exhibit possible detrimental patterns of tissue oxygen adaptation to standing, with preserved adaptation of forehead oxygenation. Further studies are needed to explore the consequences of these differences.

Increase in Synchronization of Autonomic Rhythms between Individuals When Listening to Music.

In light of theories postulating a role for music in forming emotional and social bonds, here we investigated whether endogenous rhythms synchronize between multiple individuals when listening to music. Cardiovascular and respiratory recordings were taken from multiple individuals (musically trained or music-naïve) simultaneously, at rest and during a live concert comprising music excerpts with varying degrees of complexity of the acoustic envelope. Inter-individual synchronization of cardiorespiratory rhythms showed a subtle but reliable increase during passively listening to music compared to baseline. The low-level auditory features of the music were largely responsible for creating or disrupting such synchronism, explaining ~80% of its variance, over and beyond subjective musical preferences and previous musical training. Listening to simple rhythms and melodies, which largely dominate the choice of music during rituals and mass events, brings individuals together in terms of their physiological rhythms, which could explain why music is widely used to favor social bonds.

Acute fall and long-term rise in oxygen saturation in response to meditation.

The effects of meditation on arterial and tissue oxygenation are unknown and difficult to assess because respiration is often altered, directly or indirectly, during meditation practice. Thus, changes in respiration may affect cardiovascular responses independently from meditation. In this study, we aim to isolate the specific effect of meditation on arterial and tissue oxygenation and other cardiorespiratory indexes while systematically controlling for the role of respiration. Furthermore, we aim to clarify to what extent prior expertise in meditation practice is needed to observe reliable changes. Eighty participants, half with and half without prior meditation experience, were tested while pacing breathing at predetermined rates, in the presence or absence of mantra meditation instructions, and in a body scan meditation that did not involve controlled breathing. Continuous recordings were acquired for arterial and brain oxygenation, respiratory excursion, electrocardiogram, skin vasomotion, and blood pressure. In both groups, meditation acutely decreased arterial and cerebral oxygen saturation, reduced chemoreflex sensitivity, and prolonged the RR interval, independently of respiration. Conversely, slow breathing improved heart rate variability, independently of concurrent meditation. In addition to the immediate effects of meditation, the individuals with long-term practice of meditation had overall higher arterial and cerebral oxygen saturation, overall lower blood pressure, and slower baseline respiration. Meditation acutely lowers arterial and tissue oxygenation. A repeated exposure to this condition may lead to long-term adaptation and, through increased ventilatory efficiency and improved gas exchanges, to an increase in baseline oxygenation. Meditation induces favorable changes in cardiovascular and respiratory end points of clinical interest.

Oxygen-induced impairment in arterial function is corrected by slow breathing in patients with type 1 diabetes.

Hyperoxia and slow breathing acutely improve autonomic function in type-1 diabetes. However, their effects on arterial function may reveal different mechanisms, perhaps potentially useful. To test the effects of oxygen and slow breathing we measured arterial function (augmentation index, pulse wave velocity), baroreflex sensitivity (BRS) and oxygen saturation (SAT), during spontaneous and slow breathing (6 breaths/min), in normoxia and hyperoxia (5 L/min oxygen) in 91 type-1 diabetic and 40 age-matched control participants. During normoxic spontaneous breathing diabetic subjects had lower BRS and SAT, and worse arterial function. Hyperoxia and slow breathing increased BRS and SAT. Hyperoxia increased blood pressure and worsened arterial function. Slow breathing improved arterial function and diastolic blood pressure. Combined administration prevented the hyperoxia-induced arterial pressure and function worsening. Control subjects showed a similar pattern, but with lesser or no statistical significance. Oxygen-driven autonomic improvement could depend on transient arterial stiffening and hypertension (well-known irritative effect of free-radicals on endothelium), inducing reflex increase in BRS. Slow breathing-induced improvement in BRS may result from improved SAT, reduced sympathetic activity and improved vascular function, and/or parasympathetic-driven antioxidant effect. Lower oxidative stress could explain blunted effects in controls. Slow breathing could be a simple beneficial intervention in diabetes.

Laparoscopy in children and its impact on brain oxygenation during routine inguinal hernia repair.

BACKGROUND: The systemic impact of intra-abdominal pressure (IAP) and/or changes in carbon dioxide (CO2) during laparoscopy are not yet well defined. Changes in brain oxygenation have been reported as a possible cause of cerebral hypotension and perfusion. The side effects of anaesthesia could also be involved in these changes, especially in children. To date, no data have been reported on brain oxygenation during routine laparoscopy in paediatric patients. PATIENTS AND METHODS: Brain and peripheral oxygenation were investigated in 10 children (8 male, 2 female) who underwent elective minimally invasive surgery for inguinal hernia repair. Intraoperative transcranial near-infrared spectroscopy to assess regional cerebral oxygen saturation (rScO2), peripheral oxygen saturation using pulse oximetry and heart rate (HR) were monitored at five surgical intervals: Induction of anaesthesia (baseline T1); before CO2insufflation induced pneumoperitoneum (PP) (T2); CO2PP insufflation (T3); cessation of CO2PP (T4); before extubation (T5). RESULTS: rScO2decreases were recorded immediately after T1 and became significant after insufflation (P = 0.006; rScO2decreased 3.6 ± 0.38%); restoration of rScO2was achieved after PP cessation (P = 0.007). The changes in rScO2were primarily due to IAP increases (P = 0.06). The HR changes were correlated to PP pressure (P < 0.001) and CO2flow rate (P = 0.001). No significant peripheral effects were noted. CONCLUSIONS: The increase in IAP is a critical determinant in cerebral oxygenation stability during laparoscopic procedures. However, the impact of anaesthesia on adaptive changes should not be underestimated. Close monitoring and close collaboration between the members of the multidisciplinary paediatric team are essential to guarantee the patient's safety during minimally invasive surgical procedures.

Integrated Cardio-Respiratory Control: Insight in Diabetes.

Autonomic dysfunction is a frequent and relevant complication of diabetes mellitus, as it is associated with increased morbidity and mortality. In addition, it is today considered as predictive of the most severe diabetic complications, like nephropathy and retinopathy. The classical methods of screening are the cardiovascular reflex tests and were originally interpreted as evidence of nerve damage. A more modern approach, based on the integrated control of cardiovascular and respiratory function, reveals that these abnormalities are to a great extent functional, at least in the early stage of the disease, thus suggesting new potential interventions. Therefore, this review aims to go further investigating how the imbalance of the autonomic nervous system is altered and can be influenced in many chronic pathologies through a global view of cardio-respiratory and metabolic interactions and how the same mechanisms are applicable to diabetes.

Seven Passive 1-h Hypoxia Exposures Do Not Prevent AMS in Susceptible Individuals.

PURPOSE: The present study evaluated the effects of a preacclimatization program comprising seven passive 1-h exposures to 4500-m normobaric hypoxia on the prevalence and severity of acute mountain sickness (AMS) during a subsequent exposure to real high altitude in persons susceptible to AMS. METHODS: The project was designed as a randomized controlled trial including 32 healthy female and male participants with known susceptibility to AMS symptoms. After baseline measurements, participants were randomly assigned to the hypoxia or the control group to receive the preacclimatization program (seven passive 1-h exposures within 7 d to normobaric hypoxia or sham hypoxia). After completing preacclimatization, participants were transported (bus, cog railway) to real high altitude (3650 m, Mönchsjoch Hut, Switzerland) and stayed there for 45 h (two nights). Symptoms of AMS and physiological responses were determined repeatedly. RESULTS: AMS incidence and severity did not significantly differ between groups during the high-altitude exposure. In total, 59% of the hypoxia and 67% of the control group suffered from AMS at one or more time points during the high-altitude exposure. Hypoxic and hypercapnic ventilatory responses were not affected by the preacclimatization program. Resting ventilation at high altitude tended to be higher (P = 0.06) in the hypoxia group compared with the control group. No significant between-group differences were detected for heart rate variability, arterial oxygen saturation, and hematological and ventilatory parameters during the high-altitude exposure. CONCLUSION: Preacclimatization using seven passive 1-h exposures to normobaric hypoxia corresponding to 4500 m did not prevent AMS development during a subsequent high-altitude exposure in AMS-susceptible persons.

Diagnostic role of head-up tilt test in patients with cough syncope.

AIMS: The aim of this study was to describe the head-up tilt (HUT) test and carotid sinus massage (CSM) responses, and the occurrence of syncope with coughing during HUT in a large cohort of patients. METHODS AND RESULTS: A total of 5133 HUT were retrospectively analysed to identify patients with cough syncope. Head-up tilt followed by CSM were performed. Patients were made to cough on two separate occasions in an attempt to reproduce typical clinical symptoms on HUT. Patients with cough syncope were compared with 29 age-matched control patients with syncope unrelated to coughing. A total of 29 patients (26 male, age 49 ± 14 years) with cough syncope were identified. Coughing during HUT reproduced typical prodromal symptoms of syncope in 16 (55%) patients and complete loss of consciousness in 2 (7%) patients, with a mean systolic blood pressure reduction of 45 ± 26 mmHg, and a mean increase in heart rate of 13 ± 8 b.p.m. No syncope or symptoms after coughing were observed in the control group. The HUT result was positive in 13 (48%) patients with the majority of positive HUT responses being vasodepressor (70% of positive HUT). Carotid sinus massage was performed in 18 patients being positive with a vasodepressor response causing mild pre-syncopal symptoms in only 1 patient. CONCLUSION: Syncope during coughing is a result of hypotension, rather than bradycardia. Coughing during HUT is a useful test in patients suspected to have cough syncope but in whom the history is not conclusive.

Oxygen deteriorates arterial function in type 1 diabetes.

AIMS: Although oxygen is commonly used to treat various medical conditions, it has recently been shown to worsen vascular function (arterial stiffness) in healthy volunteers and even more in patients in whom vascular function might already be impaired. The effects of oxygen on arterial function in patients with type 1 diabetes (T1D) are unknown, although such patients display disturbed vascular function already at rest. Therefore, we tested whether short-term oxygen administration may alter the arterial function in patients with T1D. METHODS: We estimated arterial stiffness by augmentation index (AIx) and the pulse wave velocity equivalent (SI-DVP) in 98 patients with T1D and 49 age- and sex-matched controls at baseline and during hyperoxia by obtaining continuous noninvasive finger pressure waveforms using a recently validated method. RESULTS: AIx and SI-DVP increased in patients (P < 0.05) but not in controls in response to hyperoxia. The increase in AIx (P = 0.05), systolic (P < 0.05), and diastolic (P < 0.05) blood pressure was higher in the patients than in the controls. CONCLUSIONS: Short-term oxygen administration deteriorates arterial function in patients with T1D compared to non-diabetic control subjects. Since disturbed arterial function plays a major role in the development of diabetic complications, these findings may be of clinical relevance.

Trained breathing-induced oxygenation acutely reverses cardiovascular autonomic dysfunction in patients with type 2 diabetes and renal disease.

AIMS: Cardiovascular autonomic dysfunction, evaluated as baroreflex sensitivity (BRS), could be acutely corrected by slow breathing or oxygen administration in patients with type 1 diabetes, thus suggesting a functional component of the disorder. We tested this hypothesis in patients with the type 2 diabetes with or without renal impairment. METHODS: Twenty-six patients with type 2 diabetes (aged 61.0 ± 0.8 years, mean ± SEM; duration of diabetes 10.5 ± 2 years, BMI 29.9 ± 0.7 kg/m(2), GFR 68.1 ± 5.6 ml/min) and 24 healthy controls (aged 58.5 ± 1.0 years) were studied. BRS was obtained from recordings of RR interval and systolic blood pressure fluctuations during spontaneous and during slow, deep (6 breaths/min) controlled breathing in conditions of normoxia or hyperoxia (5 l/min oxygen). RESULTS: During spontaneous breathing, diabetic patients had lower RR interval and lower BRS compared with the control subjects (7.1 ± 1.2 vs. 12.6 ± 2.0 ms/mmHg, p < 0.025). Deep breathing and oxygen administration significantly increased arterial saturation, reduced RR interval and increased BRS in both groups (to 9.6 ± 1.8 and 15.4 ± 2.4 ms/mmHg, respectively, p < 0.05, hyperoxia vs. normoxia). Twelve diabetic patients affected by chronic diabetic kidney disease (DKD) presented a significant improvement in the BRS during slow breathing and hyperoxia (p < 0.025 vs. spontaneous breathing during normoxia). CONCLUSIONS: Autonomic dysfunction present in patients with type 2 diabetes can be partially reversed by slow breathing, suggesting a functional role of hypoxia, also in patients with DKD. Interventions known to relieve tissue hypoxia and improve autonomic function, like physical activity, may be useful in the prevention and management of complications in patients with diabetes.

Parasympathetic Stimuli on Bronchial and Cardiovascular Systems in Humans.

BACKGROUND: It is not known whether parasympathetic outflow simultaneously acts on bronchial tone and cardiovascular system waxing and waning both systems in parallel, or, alternatively, whether the regulation is more dependent on local factors and therefore independent on each system. The aim of this study was to evaluate the simultaneous effect of different kinds of stimulations, all associated with parasympathetic activation, on bronchomotor tone and cardiovascular autonomic regulation. METHODS: Respiratory system resistance (Rrs, forced oscillation technique) and cardio-vascular activity (heart rate, oxygen saturation, tissue oxygenation index, blood pressure) were assessed in 13 volunteers at baseline and during a series of parasympathetic stimuli: O2 inhalation, stimulation of the carotid sinus baroreceptors by neck suction, slow breathing, and inhalation of methacholine. RESULTS: Pure cholinergic stimuli, like O2 inhalation and baroreceptors stimulation, caused an increase in Rrs and a reduction in heart rate and blood pressure. Slow breathing led to bradycardia and hypotension, without significant changes in Rrs. However slow breathing was associated with deep inhalations, and Rrs evaluated at the baseline lung volumes was significantly increased, suggesting that the large tidal volumes reversed the airways narrowing effect of parasympathetic activation. Finally inhaled methacholine caused marked airway narrowing, while the cardiovascular variables were unaffected, presumably because of the sympathetic activity triggered in response to hypoxemia. CONCLUSIONS: All parasympathetic stimuli affected bronchial tone and moderately affected also the cardiovascular system. However the response differed depending on the nature of the stimulus. Slow breathing was associated with large tidal volumes that reversed the airways narrowing effect of parasympathetic activation.

Slow breathing and hypoxic challenge: cardiorespiratory consequences and their central neural substrates.

Controlled slow breathing (at 6/min, a rate frequently adopted during yoga practice) can benefit cardiovascular function, including responses to hypoxia. We tested the neural substrates of cardiorespiratory control in humans during volitional controlled breathing and hypoxic challenge using functional magnetic resonance imaging (fMRI). Twenty healthy volunteers were scanned during paced (slow and normal rate) breathing and during spontaneous breathing of normoxic and hypoxic (13% inspired O2) air. Cardiovascular and respiratory measures were acquired concurrently, including beat-to-beat blood pressure from a subset of participants (N = 7). Slow breathing was associated with increased tidal ventilatory volume. Induced hypoxia raised heart rate and suppressed heart rate variability. Within the brain, slow breathing activated dorsal pons, periaqueductal grey matter, cerebellum, hypothalamus, thalamus and lateral and anterior insular cortices. Blocks of hypoxia activated mid pons, bilateral amygdalae, anterior insular and occipitotemporal cortices. Interaction between slow breathing and hypoxia was expressed in ventral striatal and frontal polar activity. Across conditions, within brainstem, dorsal medullary and pontine activity correlated with tidal volume and inversely with heart rate. Activity in rostroventral medulla correlated with beat-to-beat blood pressure and heart rate variability. Widespread insula and striatal activity tracked decreases in heart rate, while subregions of insular cortex correlated with momentary increases in tidal volume. Our findings define slow breathing effects on central and cardiovascular responses to hypoxic challenge. They highlight the recruitment of discrete brainstem nuclei to cardiorespiratory control, and the engagement of corticostriatal circuitry in support of physiological responses that accompany breathing regulation during hypoxic challenge.

Spontaneous group synchronization of movements and respiratory rhythms.

We tested whether pre-assigned arm movements performed in a group setting spontaneously synchronized and whether synchronization extended to heart and respiratory rhythms. We monitored arm movements, respiration and electrocardiogram at rest and during spontaneous, music and metronome-associated arm-swinging. No directions were given on whether or how the arm swinging were to be synchronized between participants or with the external cues. Synchronization within 3 groups of 10 participants studied collectively was compared with pseudo-synchronization of 3 groups of 10 participants that underwent an identical protocol but in an individual setting. Motor synchronization was found to be higher in the collective groups than in the individuals for the metronome-associated condition. On a repetition of the protocol on the following day, motor synchronization in the collective groups extended to the spontaneous, un-cued condition. Breathing was also more synchronized in the collective groups than in the individuals, particularly at rest and in the music-associated condition. Group synchronization occurs without explicit instructions, and involves both movements and respiratory control rhythms.

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.