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

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

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