Hypoxia Causes Glucose Intolerance in Humans

Abstract

Hypoxic respiratory diseases are frequently accompanied by glucose intolerance. We examined whether hypoxia is a cause of glucose intolerance in healthy subjects. In a double-blind within-subject crossover design, hypoxic versus normoxic conditions were induced in 14 healthy men for 30 minutes by decreasing oxygen saturation to 75% (versus 96% in control subjects) under the conditions of a euglycemic clamp. The rate of dextrose infusion needed to maintain stable blood glucose levels was monitored. Neurohormonal stress response was evaluated by measuring catecholamine and cortisol concentrations as well as cardiovascular parameters, and symptoms of anxiety. To differentiate between the effects of stress hormonal response, and hypoxia itself, on glucose intolerance, we performed hypoglycemic clamps as a nonspecific control. We found a significant decrease in dextrose infusion rate over a period of 150 minutes after the start of hypoxia (p < 0.01). Hypoxia also increased plasma epinephrine concentration (p < 0.01), heart rate (p < 0.01), and symptoms of anxiety (p < 0.05), whereas the other parameters remained unaffected. Glucose intolerance was closely comparable between hypoxic and hypoglycemic conditions (p < 0.9) despite clear differences in stress hormonal responses. Hypoxia acutely causes glucose intolerance. One of the factors mediating this effect could be an elevated release of epinephrine.

Hypoxic training: Clinical benefits on cardiometabolic risk factors

“…In healthy subjects, acute exposure to high altitude ≥3000m resulted in a reduction in insulin sensitivity in some studies [10][11][12][13][14], although glucose metabolism was enhanced, as shown in two studies [9,15] that reported a 36%-60% improvement in glucose uptake. Chronic exposure of ≥21 days, at moderate levels of altitude (1,700m-2740m) [6,9] demonstrated improvements in fasting glucose levels [6,9].…”

“…It would also suggest that patients with issues with blood regulation should monitor their blood glucose status when participating in hypoxic training involving high exercise intensities or high levels of hypoxia. Secretion of epinephrine has been suggested to be responsible for the rise in blood glucose levels and reduction in insulin sensitivity [14,15], however in one study, epinephrine levels remained unchanged despite a rise in blood glucose, indicating alternative metabolic signalling pathways [17]. Additionally hormones such as oestrogen may affect the response to hypoxic training as seen with gender differences in glucose response to hypoxic training [17].…”

“…Adverse blood glucose regulation was noted in most studies with either acute exposure to high altitude (>4,000m) [11,13,14,16] or high intensive training. However, in chronic exposure to hypoxic conditions (≥3 weeks) with moderate levels of exercise intensity showed favourable blood glucose status [6,9,15].…”

“…The increase in both SBP and DBP at higher altitudes may be attributed by the higher hypoxic stress imposed on the body, causing heightened sympathetic responses including increased secretion of hormones like epinephrine and noradrenaline [14,35]. However, it was theorized [36] that this response may be blunted due to hyperventilation, which is often associated with hypoxia.…”

“…Secondly, inconsistency of parameters made comparisons between studies challenging. For example, to measure blood glucose regulation, two studies [13,14] conducted the intravenous glucose tolerance test, while other studies measured levels of insulin [10,12] and response to an oral glucose load.…”