The Effect of Normobaric Hypoxic Confinement on Metabolism, Gut Hormones, and Body Composition

Accumulating evidence suggests that obstructive sleep apnea is associated with alterations in glucose metabolism. Although the pathophysiology of metabolic dysfunction in obstructive sleep apnea is not well understood, studies of murine models indicate that intermittent hypoxemia has an important contribution. However, corroborating data on the metabolic effects of intermittent hypoxia on glucose metabolism in humans are not available. Thus the primary aim of this study was to characterize the acute effects of intermittent hypoxia on glucose metabolism. Thirteen healthy volunteers were subjected to 5 h of intermittent hypoxia or normoxia during wakefulness in a randomized order on two separate days. The intravenous glucose tolerance test (IVGTT) was used to assess insulin-dependent and insulin-independent measures of glucose disposal. The IVGTT data were analyzed using the minimal model to determine insulin sensitivity (S(I)) and glucose effectiveness (S(G)). Drops in oxyhemoglobin saturation were induced during wakefulness at an average rate of 24.3 events/h. Compared with the normoxia condition, intermittent hypoxia was associated with a decrease in S(I) [4.1 vs. 3.4 (mU/l)(-1).min(-1); P = 0.0179] and S(G) (1.9 vs. 1.3 min(-1)x10(-2), P = 0.0065). Despite worsening insulin sensitivity with intermittent hypoxia, pancreatic insulin secretion was comparable between the two conditions. Heart rate variability analysis showed the intermittent hypoxia was associated with a shift in sympathovagal balance toward an increase in sympathetic nervous system activity. The average R-R interval on the electrocardiogram was 919.0 ms during the normoxia condition and 874.4 ms during the intermittent hypoxia condition (P < 0.04). Serum cortisol levels after intermittent hypoxia and normoxia were similar. Hypoxic stress in obstructive sleep apnea may increase the predisposition for metabolic dysfunction by impairing insulin sensitivity, glucose effectiveness, and insulin secretion.

The reason for weight loss at high altitudes is largely unknown. To date, studies have been unable to differentiate between weight loss due to hypobaric hypoxia and that related to increased physical exercise. The aim of our study was to examine the effect of hypobaric hypoxia on body weight at high altitude in obese subjects. We investigated 20 male obese subjects (age 55.7 +/- 4.1 years, BMI 33.7 +/- 1.0 kg/m(2)). Body weight, waist circumference, basal metabolic rate (BMR), nutrition protocols, and objective activity parameters as well as metabolic and cardiovascular parameters, blood gas analysis, leptin, and ghrelin were determined at low altitude (LA) (Munich 530 m, D1), at the beginning and at the end of a 1-week stay at high altitude (2,650 m, D7 and D14) and 4 weeks after returning to LA (D42). Although daily pace counting remained stable at high altitude, at D14 and D42, participants weighed significantly less and had higher BMRs than at D1. Food intake was decreased at D7. Basal leptin levels increased significantly at high altitude despite the reduction in body weight. Diastolic blood pressure was significantly lower at D7, D14, and D42 compared to D1. This study shows that obese subjects lose weight at high altitudes. This may be due to a higher metabolic rate and reduced food intake. Interestingly, leptin levels rise in high altitude despite reduced body weight. Hypobaric hypoxia seems to play a major role, although the physiological mechanisms remain unclear. Weight loss at high altitudes was associated with clinically relevant improvements in diastolic blood pressure.

Chronic hypoxia is associated with elevated sympathetic activity and hypertension in patients with chronic pulmonary obstructive disease. However, the effect of chronic hypoxia on systemic and regional sympathetic activity in healthy humans remains unknown. To determine if chronic hypoxia in healthy humans is associated with hyperactivity of the sympathetic system, we measured intra-arterial blood pressure, arterial blood gases, systemic and skeletal muscle noradrenaline (norepinephrine) spillover and vascular conductances in nine Danish lowlanders at sea level and after 9 weeks of exposure at 5260 m. Mean blood pressure was 28 % higher at altitude (P < 0.01) due to increases in both systolic (18 % higher, P < 0.05) and diastolic (41 % higher, P < 0.001) blood pressures. Cardiac output and leg blood flow were not altered by chronic hypoxia, but systemic vascular conductance was reduced by 30 % (P < 0.05). Plasma arterial noradrenaline (NA) and adrenaline concentrations were 3.7- and 2.4-fold higher at altitude, respectively (P < 0.05). The elevation of plasma arterial NA concentration was caused by a 3.8-fold higher whole-body NA release (P < 0.001) since whole-body noradrenaline clearance was similar in both conditions. Leg NA spillover was increased similarly (x 3.2, P < 0.05). These changes occurred despite the fact that systemic O2 delivery was greater after altitude acclimatisation than at sea level, due to 37 % higher blood haemoglobin concentration. In summary, this study shows that chronic hypoxia causes marked activation of the sympathetic nervous system in healthy humans and increased systemic arterial pressure, despite normalisation of the arterial O2 content with acclimatisation.