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Diagram of the study protocol, comprising measurements at t1, t2, t3, and t4. The intervention consisted of either 1 ) 6-min breathing of 13% oxygen mixture fi ve times, each separated by 6-min recovery (IH) or 2 ) placebo exposure (breathing room air with 21% FiO 2 for 1 h) in a single blind protocol. A standardized meal was given to the patients after t2 on both days. IH and placebo days were spaced at least 7 days apart.
Source publication
Hypoxemia is common in diabetes, and reflex responses to hypoxia are blunted. These abnormalities could lead to cardiovascular/renal complications. Interval hypoxia (5-6 short periods of hypoxia each day over 1-3 weeks, IH), was successfully used to improve the adaptation to hypoxia in COPD. We tested whether IH over one day could initiate a long-l...
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Context 1
... placebo-controlled single-blinded study was carried out in fi fteen patients with type 1 diabetes (2 females and 13 males) without clinical evidence of respiratory disease or de fi nite autonomic abnormalities. The protocol was approved by the ethics committee of the University of Helsinki, and the study was conducted in accordance with the ethics standards de fi ned in the Dec- laration of Helsinki. All subjects received extensive information of the study process, and written informed consent was obtained. Inclusion criteria were stable diabetes; absence of infections during the last month; absence of major cardiovascular complications such as coronary heart disease, unstable or stable angina, myocardial infarction, ventricular arrhythmias, and atrial fi brillation; therapy with b -blockers; severe hypertension ( . 180 mmHg systolic or . 110 mmHg diastolic blood pressure); de fi nite autonomic dysfunction; or proliferative retinopathy. Age limit for the selection of subjects was 20 – 45 years. All patients were on insulin treatment. In addition, fi ve patients received antihypertension medications (angiotensin receptor inhibitors [1] and ACE inhibitors [4]). The patients maintained the same therapy during IH and placebo day. The clinical and anthropometric characteristics of the participants are reported in Table 1. Measurement sessions were performed on two different days at least 5 – 7 days apart to exclude possible “ learning ” effects. On 1 day, the patients un- derwent the intermittent hypoxic protocol (hypoxia day), whereas on the other day room air was administered using the same protocol (placebo day). Baseline data were obtained in the morning of each testing day at least 2 h after breakfast. Subjects were advised to abstain from caffeinated beverages for 12 h and from alcohol for 36 h prior to testing. For avoidance of possible learning effects from one day to the other, the sequence of hypoxia or placebo day was randomized. Hypoxic or placebo exposures occurred during 1 h in the morning under standardized conditions after completion of baseline (t1) measurements (Fig. 1). During the hypoxia day, each hypoxia session consisted of fi ve hypoxic periods (13% O 2 inspired fraction of oxygen) each lasting 6 min, with fi ve normoxic intervals of same duration. During the normoxia day, the breathing program was performed in the same way, but the subjects inhaled normoxic air. On both days, participants were breathing hypoxic or normoxic air through a facial mask during the 1-h protocol. In each session, blood pressure (Finapres; FMS Medical Systems, Amsterdam, the Nether- lands) and heart rate and arterial oxygen saturation (COSMOplus; ...
Citations
... The similar IHC protocol on type 1 diabetes also yielded positive results. [84] Hypoxic exposure during exercise, in comparison to normoxic conditions, may enhance glucose uptake and insulin sensitivity in T2D patients, providing further benefits. [85] In patients diagnosed with metabolic syndrome, characterized by impaired glucose metabolism and insulin resistance, fifteen sessions of intermittent hypoxic-hyperoxic exposures appeared to improve the lipid profile, reduce systemic inflammation, and adjust cardiovascular and metabolic profiles. ...
Severe hypoxia can induce a range of systemic disorders; however, surprising resilience can be obtained through sublethal adaptation to hypoxia, a process termed as hypoxic conditioning. A particular form of this strategy, known as intermittent hypoxia conditioning hormesis, alternates exposure to hypoxic and normoxic conditions, facilitating adaptation to reduced oxygen availability. This technique, originally employed in sports and high-altitude medicine, has shown promise in multiple pathologies when applied with calibrated mild to moderate hypoxia and appropriate hypoxic cycles.
Recent studies have extensively investigated the protective role of intermittent hypoxia conditioning and its underlying mechanisms using animal models, demonstrating its potential in organ protection. This involves a range of processes such as reduction of oxidative stress, inflammation, and apoptosis, along with enhancement of hypoxic gene expression, among others.
Given that intermittent hypoxia conditioning fosters beneficial physiological responses across multiple organs and systems, this review presents a comprehensive analysis of existing studies on intermittent hypoxia and its potential advantages in various organs. It aims to draw attention to the possibility of clinically applying intermittent hypoxia conditioning as a multi-organ protective strategy. This review comprehensively discusses the protective effects of intermittent hypoxia across multiple systems, outlines potential procedures for implementing intermittent hypoxia, and provides a brief overview of the potential protective mechanisms of intermittent hypoxia.
... Hypoxia-based therapy has been applied extensively in research in a wide spectrum of healthy participants and individuals with medical conditions, and both short-and long-term effects have been investigated. Examples of previously studied treatment goals in various populations include rehabilitation in spinal cord injury (SCI) [55,[77][78][79][80][81], cardiorespiratory control in type I and II diabetes [82,83], endurance and exercise tolerance and performance in healthy and geriatric individuals [24,25,27,29,84,85], cognitive performance in geriatric and elderly individuals [22,26,28,86], cardiovascular risk factors in obese individuals [87], reducing acute mountain sickness [88], and training of respiratory dysfunction [42,48,[89][90][91]. However, clinical parameters or symptomatic efficacy of hypoxiabased therapy have thus far never been studied in PD, even though the aforementioned underlying working mechanisms of hypoxia would make PD an attractive disorder to study. ...
Background
Parkinson’s disease (PD) is a neurodegenerative disease, for which no disease-modifying therapies exist. Preclinical and clinical evidence suggest that hypoxia-based therapy might have short- and long-term benefits in PD. We present the contours of the first study to assess the safety, feasibility and physiological and symptomatic impact of hypoxia-based therapy in individuals with PD.
Methods/Design
In 20 individuals with PD, we will investigate the safety, tolerability and short-term symptomatic efficacy of continuous and intermittent hypoxia using individual, double-blind, randomized placebo-controlled N-of-1 trials. This design allows for dose finding and for including more individualized outcomes, as each individual serves as its own control. A wide range of exploratory outcomes is deployed, including the Movement Disorders Society Unified Parkinson’s Disease Rating scale (MDS-UPDRS) part III, Timed Up & Go Test, Mini Balance Evaluation Systems (MiniBES) test and wrist accelerometry. Also, self-reported impression of overall symptoms, motor and non-motor symptoms and urge to take dopaminergic medication will be assessed on a 10-point Likert scale. As part of a hypothesis-generating part of the study, we also deploy several exploratory outcomes to probe possible underlying mechanisms of action, including cortisol, erythropoietin and platelet-derived growth factor β. Efficacy will be assessed primarily by a Bayesian analysis.
Discussion
This evaluation of hypoxia therapy could provide insight in novel pathways that may be pursued for PD treatment. This trial also serves as a proof of concept for deploying an N-of-1 design and for including individualized outcomes in PD research, as a basis for personalized treatment approaches.
Trial registration
ClinicalTrials.gov Identifier: NCT05214287 (registered January 28, 2022).
... The study was approved by the Regional Ethical Review Board in Stockholm, Sweden, and carried out in accordance with the principles of the Declaration of Helsinki. The sample size has been decided according to the experience from previous studies (Duennwald et al., 2013). All participants in the study provided informed consent. ...
... The effect of hypoxia on ROS production was evaluated in patients with poorly controlled type 1 diabetes (28.9 ± 7.2 years old; HbA1c: 74.4 ± 11.8 mmol/mol) and matched control subjects without diabetes (30.5 ± 8.5 years old; HbA1c: 35.5 ± 2.6 mmol/mol). Participants were exposed to mild and intermittent hypoxia (13% O 2 ) for 1 hr (Figure 1-figure supplement 1), which is known to elicit a clinical response (Duennwald et al., 2013). As shown in Figure 1, ROS levels in peripheral blood were increased by hypoxia in patients with 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.
... The effect of hypoxia on ROS production was evaluated in patients with poorly controlled type 1 diabetes (28.9 ± 7.2 years old; HbA1c: 74.4 ± 11.8 mmol/mol) and matched control subjects without diabetes (30.5 ± 8.5 years old; HbA1c: 35.5 ± 2.6 mmol/mol). Participants were exposed to mild and intermittent hypoxia (13% O2) for 1 hour ( Fig. 1 -figure supplement 1), which is known to elicit a clinical response (Duennwald et al., 2013). As shown in Fig. 1, ROS levels in peripheral blood were significantly increased by hypoxia in patients with diabetes. ...
... NCT02629406) was approved by the Regional Ethical Review Board in Stockholm, Sweden, and carried out in accordance with the principles of the Declaration of Helsinki. The sample size has been decided according to the experience from previous studies (Duennwald et al., 2013). All participants in the study provided informed consent. ...
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 dynamic of ROS levels was analysed in the blood of healthy subjects and individuals with type 1 diabetes after exposure to hypoxia (ClinicalTrials.gov registration no. NCT02629406). 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) and was followed by functional consequences. 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 highly significant and timely since the first PHD inhibitor that can activate HIF-1 has been newly approved for clinical use.
... The effectiveness of interval Hyp, Hyp training and Hyp and single Ex in increasing cardiorespiratory, metabolic and glycaemic control, in healthy individuals and patients with diabetes has been demonstrated in recent studies. [32][33][34] The studies have shown that Hyp stimulates glucose transport in INS-resistant human skeletal muscles and, when combined with Ex, improves INS sensitivity in T2D and prevents vascular complications in T1D. [34][35][36] Hypoxic Ex training significantly increased serum irisin concentrations in diet-induced obese rats. ...
Aim
This study aimed to determine the effect of moderate intensity continuous exercise (Ex) and hypoxia (Hyp) on serum brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1) and its binding protein-3 (IGFBP-3), irisin and cytokines levels in patients with type 1 diabetes (T1D).
Methods
A total of 14 individuals with T1D (age: 28.7 ± 7.3 years) and 14 healthy adults (age: 27.1 ± 3.9 years) performed 40-min continuous Ex at moderate intensity (50% lactate threshold) on a cycle ergometer in normoxia (Nor) and Hyp (FiO 2 = 15.1%) Biochemical factors, glucose concentrations and physiological variables were measured at rest, immediately and up to 24 h after both Ex protocols.
Results
Patients with T1D had significantly lower pre-Ex serum concentrations of BDNF ( p < 0.05, p < 0.01), and total IGF-1 ( p < 0.001, p < 0.05) and significantly higher irisin levels ( p < 0.05, p < 0.01) in Nor and Hyp, compared with healthy subjects. Ex significantly increased in T1D group serum BDNF (in Nor only p < 0.05) and total IGF-1 levels in Nor and Hyp ( p < 0.001 and p < 0.01, respectively). Immediately after Ex in Hyp, freeIGF-1 ( p < 0.05) and irisin levels ( p < 0.001) were significantly higher compared with the levels induced by Ex alone. Free IGF-1 and irisin serum levels remained elevated in 24 h post-Ex in Hyp. In T1D, significant blood glucose (BG) decrease was observed immediately after Ex in Hyp ( p < 0.001) and in 24 h recovery ( p < 0.001) compared with pre-Ex level.
Conclusion
The study results suggest that moderate intensity continuous Ex has beneficial effect on BDNF and IGF-1 levels. Ex in hypoxic conditions may be more effective in increasing availability of IGF-1. The alterations in the post-Ex irisin levels and IGF-1 system may be contributing to more effective glycaemia control in patients with T1D.
... Hypoxic training is commonly used to increase muscle oxidative capacity [1,2] and exercise performance [3]. e beneficial effects of adaptation to hypoxia have been used for cardiorespiratory control [4,5], for prevention of metabolic disorders [4,6], and to induce an improvement in athletic performance and high-altitude acclimatization [7][8][9]. e mechanisms responsible for these benefits can be grouped into three major categories: adaptation of organs and tissues responsible for oxygen transport [10,11], improvements in cardiovascular hemodynamics [12][13][14], and adaptive changes in the immune system [15,16]. ...
... Hypoxic training is commonly used to increase muscle oxidative capacity [1,2] and exercise performance [3]. e beneficial effects of adaptation to hypoxia have been used for cardiorespiratory control [4,5], for prevention of metabolic disorders [4,6], and to induce an improvement in athletic performance and high-altitude acclimatization [7][8][9]. e mechanisms responsible for these benefits can be grouped into three major categories: adaptation of organs and tissues responsible for oxygen transport [10,11], improvements in cardiovascular hemodynamics [12][13][14], and adaptive changes in the immune system [15,16]. ...
... Chronic exposure to hypoxia improves oxygen transport by enhancing erythropoietin secretions and the consequential increase in total hemoglobin mass [22,23], increases cardiorespiratory reserve [5,11], and improves autonomic nervous system function [4,11] and skeletal muscle oxidative capacity [10,24,25]. e precise molecular mechanism responsible for cardiovascular adaptation in response to hypoxia during exercise training is still not well understood. ...
Aims:
The study investigated the effect of high-intensity interval training in hypoxia and normoxia on serum concentrations of proangiogenic factors, nitric oxide, and inflammatory responses in healthy male volunteers.
Methods:
Twelve physically active male subjects completed a high-intensity interval training (HIIT) in normoxia (NorTr) and in normobaric hypoxia (HypTr) (FiO2 = 15.2%). The effects of HIIT in hypoxia and normoxia on maximal oxygen uptake, hypoxia-inducible factor-1-alpha, vascular endothelial growth factor, nitric oxide, and cytokines were analyzed.
Results:
HIIT in hypoxia significantly increases maximal oxygen uptake (p=0.01) levels compared to pretraining levels. Serum hypoxia-inducible factor-1 (p=0.01) and nitric oxide levels (p=0.05), vascular endothelial growth factor (p=0.04), and transforming growth factor-β (p=0.01) levels were increased in response to exercise test after hypoxic training. There was no effect of training conditions for serum baseline angiogenic factors and cytokines (p > 0.05) with higher HIF-1α and NO levels after hypoxic training compared to normoxic training (F = 9.1; p < 0.01 and F = 5.7; p < 0.05, respectively).
Conclusions:
High-intensity interval training in hypoxia seems to induce beneficial adaptations to exercise mediated via a significant increase in the serum concentrations of proangiogenic factors and serum nitric oxide levels compared to the same training regimen in normoxia.
... The exposure (6 h/ day for 42 days) to hypobaric hypoxia at a pressure corresponding to 3 000 m altitude, restored hyperglycaemia effect on the heart of the rats with streptozotocin-induced T1D, by reducing the tissue injury and increasing capillarity [26]. Pavan et al. [27] demonstrated that the metabolic and cardiovascular parameters of T1D patients were comparable with those of control subjects during extreme altitude (3 700 and 5 800 m) mountaineering, suggesting good adaptive response to Hx. Duennwald et al. [28] demonstrated that T1D individuals exposed to intermittent hypoxia (FiO₂ = 13.0 %) (5 × 6 min each day over 1-3 weeks) had improved ventilatory reflexes to Hx. The study by Zebrowska et al. [29] showed that shorttime hypoxia (FiO₂ = 15.1 %) combined with graded exercise allowed more effective glycaemia control in T1D patients when compared with the exercise in normoxia. ...
... Consequently, neutrophils lose the diapedesis ability, as they plug the lumen of the vessel, leading to local hypoxia, and potentially to angiogenesis intensification in some tissues [56]. Reports have shown that intermittent hypoxia treatment may have potential therapeutic effect and induce adaptive response to chronic hypoxia [28]. ...
Objectives The aim of the study was to assess the effect of continuous and intermittent exercise in hypoxia on glycaemic control and selected markers of vascular function in patients with Type 1 diabetes (T1D).
Methods 12 patients suffering from T1D for 12.1±6.0 years and 12 healthy adults performed: continuous exercise (ExC) and intermittent exercise (ExInt) in normoxia and hypoxia (FiO₂=15.1%). Glycaemia and proangiogenic factors concentrations were measured at rest and immediately after exercise.
Results T1D patients’ glycaemia decreased in response to ExC (p<0.01) and ExInt (p<0.05) under hypoxic conditions. ExInt in normoxia (p<0.05) and hypoxia (p<0.05) reduced HIF-1α in the T1D group. A tendency for vascular endothelial growth factor to increase after ExInt in hypoxia (6.0±3.8 vs. 17.1±13.07 pg/mL) and a proinflammatory cytokine TNF-α level to decrease (33.2±19.1 vs. 25.1±14.4 pg/mL) was found in the same group.
Conclusions Combining exercise with hypoxia may allow more effective short-term glycaemic control in T1D. Intermittent exercise with hypoxia could stabilize the secretion of selected proangiogenic factors and reduce inflammation, potentially leading to improved vascular function.
... [4][5][6][7] IHT also positively affects autonomic nervous system functioning in various patients. 8,9 This technique consists of intermittent exposures to hypoxicnormoxic stimuli (1 cycle of up to 5 hypoxic exposures lasting at least 5-6 minutes, followed by at least 5-6 minutes of normoxic air breathing) repeated almost daily (4-5 days a week) over 2 to 3 weeks. In our study we used normobaric intermittent hypoxic-hyperoxic training (IHHT) as a new alternative treatment. ...
Background:
Repeated exposure to intermittent normobaric hypoxia improves exercise tolerance in cardiac patients. Little is known on the effects of intermittent normobaric hypoxia-hyperoxia exposure in coronary artery disease (CAD) patients (New York Heart Association II-III).
Hypothesis:
IHHT improves exercise tolerance, cardiometabolic profile, and quality of life in CAD patients.
Methods:
The study design was a nonrandomized, controlled, before-and-after trial. Forty-six CAD patients volunteered to take part in the study: a group of 27 patients undertook the intermittent hypoxia (O2 at 10%)-hyperoxia (O2 at 30%) training (IHHT), whereas a control group (CTRL) of 19 patients, who already completed an 8-week standard cardiac rehabilitation program, was allocated to sham-IHHT treatment (breathing room air, O2 at 21%). Exercise performance, blood and metabolic profiles, and quality of life (Seattle Angina Questionnaire [SAQ]) were measured before and after in the IHHT group (IHHG) and sham-IHHT in the CTRL group.
Results:
The IHHG showed improved exercise capacity, reduced systolic and diastolic blood pressures, enhanced left ventricle ejection fraction, and reduced glycemia, but only at 1-month follow-up. Angina as a reason to stop exercising was significantly reduced after treatment and at 1-month follow-up. The IHHT SAQ profile was improved in the IHHG and not significantly different to the CTRL group after standard rehabilitation. The IHHG was also compared to the CTRL group at 1-month follow-up, and no differences were found.
Conclusions:
In CAD patients, an IHHT program is associated with improved exercise tolerance, healthier risks factors profile, and a better quality of life. Our study also suggests that IHHT is as effective as an 8-week standard rehabilitation program.
... In addition, the same results (improvement in tissue oxygenation, reduction of chemoreflex activation, improvement in parasympathetic activity and BRS, increase in antioxidant reserve, and reduced free radical excess) that can be obtained with slow breathing also occur with physical exercise (Table 1). This review then suggests a rather new reason for encouraging physical exercise in diabetes, in addition to other potential treatments, like hypoxic training [20,81] or drugs which stabilize and activate HIF [82]. All these interventions, based on the knowledge of the cardio-respiratory reflex interaction, have the potential to be helpful in improving the autonomic dysfunction and the sensitivity to hypoxia and finally prevent diabetic complications. ...
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.
... It is important to note, changes in HRV may be affected by changes in ventilation [8]. Changes in ventilation, however, are unlikely to influence present findings because: 1) The ventilatory response to hypoxia in patients with type 1 diabetes is blunted [7,13,20,33], 2) A hypoxic ventilatory decline occurs with sustained hypoxemia [25], and 3) Measures of respiratory rate were not significantly different between baseline, normoxic hypoglycemia, and hypoxic hypoglycemia (n=4; Normoxia: 14±1 to 15±2 breath/min; Hypoxia: 13±1 to 15±2 breath/min; Effect of gas, p>0.05; Interaction of gas and time, p>0.05). ...
Patients with type 1 diabetes mellitus exhibit impairments in autonomic and cardiovascular control which are worsened with acute hypoglycemia--thus increasing the risk of adverse cardiovascular events. Hypoxia, as seen with the common comorbidity of sleep apnea, may lead to further autonomic dysfunction and an increased risk of ventricular arrhythmias. Therefore, we hypothesized that heart rate variability (HRV) and baroreflex sensitivity (BRS) would be reduced during hypoglycemia in adults with type 1 diabetes, with a further decline when combined with hypoxia.
Subjects with type 1 diabetes (n = 13; HbA1c = 7.5 ± 0.3 %, duration of diabetes = 17 ± 5 yrs) completed two 180 min hyperinsulinemic (2 mU/kg TBW/min), hypoglycemic (~3.3 µmol/mL) clamps separated by a minimum of 1 week and randomized to normoxia (SpO2 ~98 %) or hypoxia (SpO2 ~85 %). Heart rate (electrocardiogram) and blood pressure (finger photoplethysmography) were analyzed at baseline and during the hypoglycemic clamp for measures of HRV and spontaneous cardiac BRS (sCBRS).
Hypoglycemia resulted in significant reductions in HRV and sCBRS when compared with baseline levels (main effect of hypoglycemia: p < 0.05). HRV and sCBRS were further impaired during hypoxia (main effect of hypoxia: p < 0.05).
Acute hypoxia worsens hypoglycemia-mediated impairments in autonomic and cardiovascular control in patients with type 1 diabetes and may increase the risk of cardiovascular mortality. These results highlight the potential cumulative dangers of hypoglycemia and hypoxia in this vulnerable population.
