Impact of Intermittent Hypoxia on the Glycemic Response to an Oral Glucose Tolerance Test

Hypoxia triggers glucose uptake independently from the action of insulin. PURPOSE: To determine the acute effect of intermittent hypoxia, defined as alternating short bouts of breathing hypoxic and room air, on plasma glucose levels during an oral glucose tolerance test in healthy individuals. We hypothesized that exposure to intermittent hypoxia would attenuate the increase in glucose levels in response to an oral glucose tolerance test. METHODS: Nine individuals (5 men, age: 24 ± 4 years, height: 175 ± 9 cm, weight: 71.0 ± 13.5 kg, HbA1c: 5.4 ± 0.1%) participated in the study. Participants visited the laboratory on two occasions. On both visits, a 2-hour oral glucose tolerance test was performed, with venous blood samples collected 0, 30, 60, 90 and 120 minutes following the ingestion of a 75 g glucose drink. On visit 1, an intermittent hypoxia (IH) protocol, consisting of eight 4-minute hypoxic cycles at a targeted arterial oxygen saturation of 80% interspersed with breathing room air to resaturation, was performed following ingestion of the glucose drink. On visit 2, an intermittent normoxia protocol consisting of eight 4-minute normoxic cycles interspersed with breathing room air was performed following ingestion of the glucose drink. Visit order was randomized and participants were blinded to the condition. RESULTS: As expected, intermittent hypoxia resulted in a lower arterial oxygen saturation than intermittent normoxia (IH: 83 ± 3, IN: 98 ± 1%, p \u3c 0.01) which corresponded to lower levels of inspired oxygen (IH: 10.9 ± 0.7, IN: 20.9 ± 0.3%, p \u3c 0.01). Plasma glucose responses to the oral glucose tolerance test were not different between conditions (IH vs. IN: 0: 90 ± 7 vs. 89 ± 6; 30: 135 ± 21 vs. 137 ± 24; 60: 110 ± 28 vs. 108 ± 25; 90: 96 ± 18 vs. 88 ± 14; and 120: 101 ± 19 vs. 83 ± 14 mg/dl, p = 0.29). Intermittent hypoxia triggered an increase in cardiac output (6.1 ± 0.9 to 6.8 ± 1.3 L/min, p \u3c 0.01) caused by an increase in heart rate (67 ± 10 to 79 ± 12 bpm, p \u3c 0.01). CONCLUSION: Contrary to our hypothesis, intermittent exposure to hypoxia did not attenuate the increase in plasma glucose levels during an oral glucose tolerance test in individuals with normal glycemic control. It remains to be determined whether intermittent hypoxia can attenuate the increase in plasma glucose levels in response to an oral glucose tolerance test in individuals with impaired glucose tolerance

Impaired Erythropoietin Response to a Single Session of Intermittent Hypoxia in Patients with Type 2 Diabetes

Patients with type 2 diabetes (T2D) exhibit, on average, a 20% decline in maximal oxygen consumption when compared to healthy adults. Hemoglobin mass strongly correlates to maximal oxygen consumption. A reduced total blood volume has been observed in patients with T2D, suggesting that a reduced hemoglobin mass contributes to the decreased maximal oxygen consumption in this population. Hypoxia stimulates the release of erythropoietin (EPO), the hormone regulating red blood cell production. We previously showed that intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, increases EPO levels. PURPOSE: To determine the effect of a single session of intermittent hypoxia on serum EPO levels and hemoglobin mass in patients with T2D. We hypothesized that a single session of intermittent hypoxia would raise serum EPO levels and lead to an increase in hemoglobin mass in patients with T2D. METHODS: Ten patients with T2D (4 women, age: 53 ± 10 years, body mass index: 36.2 ± 8.5 kg/m2, HbA1c: 7.2 ± 1.2%) were exposed to an intermittent hypoxia protocol consisting of eight 4-min cycles at a targeted oxygen saturation of 80% interspersed with normoxic cycles to resaturation. Air was made hypoxic by titrating nitrogen into a breathing circuit. Pulmonary gas exchange, oxygen saturation, and hemodynamics were continuously measured throughout the protocol. EPO levels were measured before and 4.5 hours after the beginning of the protocol. Hemoglobin mass was assessed via carbon monoxide rebreathing before and seven days following intermittent hypoxia. RESULTS: Intermittent hypoxia lowered oxygen saturation (­­97 ±­ 2 to 81 ± 2%, p\u3c0.01), which resulted from a lower fraction of inspired oxygen (20.8 ±­ 0.1 to 11.1 ± 1.0%, p\u3c0.01). There was no significant change in EPO levels following exposure to intermittent hypoxia (11.9 ± 5.3­ to 12.1 ± 4.3 mU/ml, p=0.83). There was also no change in hemoglobin mass in response to intermittent hypoxia (864 ± 152­ to 850 ± 150 g, p=0.64). Intermittent hypoxia did not affect mean arterial pressure (94 ± 5 to 97 ± 7 mmHg, p=0.18) but increased cardiac output (9.1 ± 2.7 to 9.8 ± 2.8 L/min, p=0.03) due to an increase in heart rate (78 ± 9 to 84 ± 10 bpm, p\u3c0.01). CONCLUSION: A single session of intermittent hypoxia did not increase serum EPO levels or hemoglobin mass in patients with T2D. These findings suggest an impaired EPO response to decreased oxygen levels in patients with T2D, which may contribute to the reduced hemoglobin mass and total blood volume observed in this population

The Influence of Intermittent Hypoxia on Erythropoietin Levels in Older Adults

Few minutes of hypoxia exposure stabilizes hypoxia-inducible factors, resulting in erythropoietin (EPO) gene transcription and production. A brief intermittent hypoxia exposure increased EPO levels in young healthy adults, suggesting that a single session of intermittent hypoxia has the potential to increase oxygen-carrying capacity. PURPOSE: To determine the effect of a single session of intermittent hypoxia on serum EPO levels and hemoglobin mass among older adults. We hypothesized that a single session of intermittent hypoxia would raise serum EPO levels and lead to an increase in hemoglobin mass in older adults. METHODS: Seventeen participants (8 women, age: 54 ± 8 years, height: 177 ± 10 cm, weight: 76 ± 14 kg, BMI: 24 ± 4 kg/m2) were randomly assigned to an intermittent hypoxia group (IH, n=11) or an intermittent normoxia group (IN, n=6). Intermittent hypoxia consisted of eight 4-minute cycles at a targeted arterial oxygen saturation of 80% interspersed with normoxic cycles to resaturation. Air was made hypoxic by titrating nitrogen into the breathing circuit. Intermittent normoxia consisted of the same protocol, but nitrogen was not added to the breathing circuit. Pulmonary gas exchange, arterial oxygen saturation, and hemodynamics were continuously measured throughout both protocols. EPO levels were measured before and 4.5 hours after the beginning of each protocol. Hemoglobin mass was assessed via carbon monoxide rebreathing the day before and seven days following intermittent hypoxia or normoxia. RESULTS: Intermittent hypoxia lowered arterial oxygen saturation (­­98 ±­ 1 to 82 ± 3 %, p\u3c0.01), which resulted in a lower fraction of inspired oxygen (20.8 ±­ 0.1 to 10.9 ± 1.0 %, p\u3c0.01). There was no significant change in EPO levels in either condition (IH:10.4 ±­ 2.9 to 13.3 ± 4.2; IN: 5.6 ±­ 2.4 to 6.5 ± 2.9 mU/ml, main effect for time p=0.12). Similarly, there was no change in hemoglobin mass in response to both conditions (IH: 752 ±­ 189 to 754 ± 189; IN: 858 ± 177 to 879 ± 157 g, main effect for time p=0.87). Intermittent hypoxia did not affect mean arterial pressure (87 ± 15 to 88 ± 14 mmHg, p=0.18) or cardiac output (5.5 ± 1.5 to 5.7 ± 1.5 L/min, p=0.22), but increased heart rate (62 ± 9 to 68 ± 9 bpm, p\u3c0.01). CONCLUSION: A single session of eight 4-minute cycles of intermittent hypoxia did not increase serum EPO levels in older adults

Intermittent Hypoxia Increases Erythropoietin Levels in Healthy Individuals

Few minutes of hypoxic exposure stabilizes hypoxia-inducible factor-1α, resulting in erythropoietin (EPO) gene transcription and production. PURPOSE: The objective of this study was to identify the shortest intermittent hypoxia protocol necessary to increase serum EPO levels in healthy individuals. We hypothesized that two separate intermittent hypoxia protocols would significantly increase EPO levels in healthy individuals. METHODS: A total of seven individuals (4 women and 3 men, age: 28±7 years, height: 177±9 cm, weight: 79.7±18.4 kg) participated in the study. In Experiment 1, the spontaneous EPO changes under normoxia (NORM) and the EPO response to five 4-minute cycles of intermittent hypoxia (IH5) were determined in six individuals. In Experiment 2, the EPO response to eight 4-minute cycles of intermittent hypoxia (IH8) and 120 minutes of continuous hypoxia (CONT) was determined in six individuals. All hypoxic protocols were performed at a targeted arterial oxygen saturation of 80%. Air was made hypoxic by titrating nitrogen into a breathing circuit. Pulmonary gas exchange, arterial oxygen saturation, and hemodynamics obtained by finger plethysmography were continuously monitored throughout all hypoxic protocols. In Experiment 1, EPO levels were measured before, 2.5 and 4.5 hours after the beginning of the IH5 and NORM protocols. In Experiment 2, EPO levels were measured before, 4.5 and 6 hours after the beginning of the IH8 and CONT protocols. RESULTS: There was no significant change in EPO levels in response to normoxia or in response to five cycles of intermittent hypoxia (NORM: 9.5±1.8 to 10.5±1.8, IH5: 11.4±2.3 to 13.4±2.1 mU/ml, main effect for time p=0.35). There was an increase in EPO levels in response to eight cycles of intermittent hypoxia and 120 minutes of continuous hypoxia, with peak levels observed 4.5 hours after the onset of hypoxia (IH8: 11.2±2.0 to 16.7±2.2, CONT: 11.1±3.8 to 19.4±3.8 mU/ml, main effect for time p˂0.01). Eight cycles of intermittent hypoxia increased EPO levels to a similar extent as 120 minutes of continuous hypoxia (main effect for condition p=0.36). Intermittent hypoxia did not affect mean arterial pressure (IH5: 88±7 to 87±7, IH8: 90±7 to 88±7 mmHg, p\u3e0.05). CONCLUSION: Eight 4-minute cycles of intermittent hypoxia represent the shortest protocol to increase serum EPO levels in healthy individuals

Hypoxic Preconditioning Attenuates Ischemia-reperfusion Injury in Older Adults

Sudden restoration of blood flow to an ischemic vessel paradoxically damages endothelial cells. In young healthy adults, ischemic preconditioning, caused by repeated periods of brief ischemia induced by local cuff inflation prior to reperfusion, attenuates endothelial dysfunction following an ischemia-reperfusion injury. However, ischemic preconditioning does not consistently protect against ischemia-reperfusion injury in older adults. Intermittent systemic hypoxemia, induced via brief bouts of breathing low levels of oxygen, attenuates endothelial dysfunction following an ischemia-reperfusion injury in young adults. PURPOSE: To determine whether intermittent hypoxia protects against ischemia-reperfusion injury in older adults. METHODS: Twelve older adults (5 women, age: 57 ± 9 years, height: 173 ± 8 cm, body weight: 75.8 ± 13.4 kg) visited the laboratory on two separate occasions. Endothelium-dependent vasodilation was assessed by brachial artery flow-mediated dilation using a semiautomated diagnostic ultrasound system before and after 20 minutes of upper arm blood flow occlusion to induce an ischemia-reperfusion injury. Blood flow occlusion was preceded by either intermittent hypoxia, consisting of three 4-minute hypoxic cycles at a targeted arterial oxygen saturation of 80% interspersed with 4-minute room air cycles, or intermittent normoxia, consisting of three 4-minute normoxic cycles separated by 4-minute room air cycles. RESULTS: Intermittent hypoxia resulted in an arterial oxygen saturation of 80 ± 2%, which corresponded to oxygen levels of 11.4 ± 0.7%. When preceded by intermittent normoxia, blood flow occlusion reduced flow-mediated dilation by 4.1 ± 2.6% (6.5 ± 1.7 to 2.4 ± 1.7%). In contrast, flow-mediated dilation was reduced by 2.0 ± 1.5% when blood flow occlusion was preceded by intermittent hypoxia (5.6 ± 1.7 to 3.6 ± 2.3%, P = 0.03). When compared to intermittent normoxia, intermittent hypoxia resulted in a greater heart rate (60 ± 10 vs. 68 ± 10 bpm, P \u3c 0.01) but did not affect cardiac output (5.1 ± 1.4 vs. 5.8 ± 1.8 L/min, P = 0.11). CONCLUSION: Hypoxic preconditioning attenuated the reduction in flow-mediated dilation induced by a 20-minute blood flow occlusion in older adults. Thus, exposure to intermittent hypoxia represents a promising strategy to protect against ischemia-reperfusion injury in populations at risk for ischemic events

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Erythropoietin response to intermittent hypoxia in health and type 2 diabetes

Patients with type 2 diabetes and aging individuals experience declines in maximal oxygen consumption. Hemoglobin mass, a component of oxygen transport, strongly correlates to maximal oxygen consumption. Interventions that increase hemoglobin mass may therefore increase maximal oxygen consumption in older adults and patients with type 2 diabetes. Intermittent hypoxia, characterized by alternating periods of breathing low levels of oxygen interspersed with periods breathing normoxic air, has the potential to elicit an acute increase in erythropoietin levels and hemoglobin mass. Despite several instances of repeated exposures to intermittent hypoxia increasing red blood cell count over the course of five days to three weeks, there exists a lack of consistent stimuli across the literature, with deviations in hypoxic duration, number of cycles, and hypoxic severity. Furthermore, studies that successfully increased oxygen transport following intermittent hypoxia did not measure erythropoietin levels, the hormone regulating red cell production, thereby eliminating the possibility for protocol comparison. Therefore, the following three studies aimed to identify the shortest intermittent hypoxia protocol to increase erythropoietin levels in healthy young individuals, and to apply this intermittent hypoxia protocol to older individuals and patients with type 2 diabetes, with the goal of potentially increasing hemoglobin mass. In the first study, we identified the shortest hypoxic protocol within the literature to increase EPO concentrations among young healthy adults. The EPO response to the 32 total hypoxic minutes was no different than a 2-hour continuous hypoxia protocol. In the second study, we demonstrated that EPO concentrations increased following the same intermittent hypoxia in middle-aged adults but found no increase to hemoglobin mass. In the third study, we demonstrated a lack of EPO response to intermittent hypoxia in patients with type 2 diabetes. Furthermore, this study was the first to report hemoglobin mass levels in patients with type 2 diabetes. Collectively, the overall findings highlight the acute effects of intermittent hypoxia on erythropoietin in health and type 2 diabetes.Kinesiology and Health Educatio

The cardiovascular and metabolic effects of high-intensity interval training with and without high-altitude simulation and either with and without high-concentration oxygen recovery assistance

Advisors: Peter Chomentowski.Committee members: Craig Broeder; Anthony Deldin.Includes bibliographical references.Includes illustrations.Purpose: The study investigated the acute responses of altitude (Denver, CO) simulation during high intensity interval training and the subsequent supplementation of oxygen to facilitate greater recovery. Lacking literature on the subject matter is a major consideration for completion of the study. We hypothesize that oxygen supplementation during an acute bout of high intensity interval training with accompanying altitude will allow for greater recovery. Methods: Seven healthy cyclists aged 40.9 +/- 7.01 (Height: 68.4 +/- 4.98: Weight: 171.3 +/- 33.29: 19.3% +/-7.41%: VO2 Max L/min 4.12 +/- 1.17) performed baseline VO2max testing and three subsequent separate randomized trials consisting of three HIIT and recovery intervals with varying conditions. Session A: altitude intervals / supplemental oxygen recovery. Session B: sea level HIIT / sea level recovery. Session C: altitude HIIT / sea level recovery. Trial intensity will be established by cardiac output prediction and set at 75% HIIT and 50% recovery in watts. Results: Supplemental oxygen following HIIT elicited significant responses in HR (p<0.035, p<0.012), VO2 (p<0.029, p<0.030, p<0.004, p<0.001), cardiac output (p<0.012, p<0.002), and right quadricep oxygen saturation (p<0.011, p<0.013, p<0.009). Conclusion: The implementation of supplemental oxygen following altitude simulation with HIIT will facilitate greater recovery. Although significance was found among multiple variables, more subjects are needed for other to become significant.M.S. Ed. (Master of Education