Hypoxia-induced impairments in fasting glucose are associated with acute mountain sickness severity during 4 days of residence at 4,300 m.

Insulin resistance has been associated with acute mountain sickness (AMS) risk, but the influence of active ascent is unclear. Thirty-two unacclimatized soldiers (23 ± 4 yr; 80 ± 14 kg) were tested at baseline residence (BLR), hiked ∼5 km (n = 16) or were driven (n = 16) to 4,300 m, and stayed for 4 days (∼66 h). Venous blood was taken each morning at BLR and during high altitude (HA) exposure days 2-4 (HA2-4) and the evening on day 1 at HA (HA1). Metabolites and hormones were measured, and insulin resistance (HOMA-IR) was calculated. AMS cerebral factor score (AMS-C) was measured daily and peak scores were calculated. Active ascenders had higher energy expenditure (1,265 ± 351 vs. 408 ± 208 kcal) and lower oxygen saturation ([Formula: see text]) (75 ± 3 vs. 82 ± 3%) during ascent. Norepinephrine and lactate were higher (P < 0.007) in active ascenders on HA1. All other data were combined due to lack of group differences. Glucose, insulin, and HOMA-IR were elevated (P < 0.05) on HA2 (105.9 ± 12.3 mg/dL; 12.1 ± 6.8 µIU/mL; 3.2 ± 2.1 au) and HA3 (101.8 ± 11.2 mg/dL; 10.2 ± 5.5 µIU/mL; 2.2 ± 1.4 au) vs. baseline and returned to normal on HA4. Epinephrine (P < 0.001) and cortisol (P = 0.004) were elevated on HA1 and HA2 vs. baseline, respectively. GLP-1 was higher on HA1 vs. HA2 and HA3 (P < 0.021). Glucose (rrm = 0.42; P = 0.001), insulin (rrm = 0.29; P = 0.001), HOMA-IR (rrm = 0.27; P = 0.002), epinephrine (rrm = 0.34; P < 0.001), and norepinephrine (rrm = 0.20; P = 0.027) were significantly correlated with AMS-C. Transient perturbations to glucose metabolism during 4 days of HA exposure influences AMS severity without further impact from active ascent.NEW & NOTEWORTHY We demonstrate insulin resistance during 4 days of exposure at 4,300 m is positively correlated with acute mountain sickness (AMS) severity. This builds on previous data showing insulin sensitivity and carbohydrate metabolism at sea-level predict AMS. The blood glucose excursions appear at least partly mediated by cortisol and nocturnal hypoxemia.