Effects of acute intermittent hypoxia on glucose metabolism in awake healthy volunteers

Abstract

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.

Figures

Fig. 1.

Schematic of the experimental setup illustrating the breathing circuit with the 2 inspiratory pathways connected to pressurized ambient air (21% O2) or a hypoxic gas mixture (95% N2 and 5% O2).

Fig. 2.

Oxyhemoglobin saturation (SpO2) profile from 1 subject along with a 5-min expanded view of the fractional inspired oxygen concentration (FiO2). The electrocardiogram during 1 hypoxic event is also shown. IVGTT, intravenous glucose tolerance test.

Fig. 3.

Values of insulin sensitivity (SI), the disposition index (DI = SI × AIRg, where AIRg is acute insulin response to glucose), glucose effectiveness (SG), and glucose effectiveness at zero insulin (GEZI) with intermittent hypoxia and normoxia. Values are means and SEs of the mean.