Women at altitude: short-term exposure to hypoxia and/or alpha(1)-adrenergic blockade reduces insulin sensitivity

After short-term exposure to high altitude (HA), men appear to be less sens itive to insulin than at sea level (SL). We hypothesized that the same woul d be true in women, that reduced insulin sensitivity would be directly rela ted to the rise in plasma epinephrine concentrations at altitude, and that the addition of alpha -adrenergic blockade would potentiate the reduction. To test the hypotheses, 12 women consumed a high-carbohydrate meal at SL an d after 16 h at simulated 4,300-m elevation (HA). Subjects were studied twi ce at each elevation: once with prazosin (Prz), an alpha (1)-adrenergic ant agonist, and once with placebo (Pla). Mathematical models were used to asse ss insulin resistance based on fasting [homeostasis model assessment of ins ulin resistance (HOMA-IR)] and postprandial [composite model insulin sensit ivity index (C-ISI)] glucose and insulin concentrations. Relative to SL-Pla (HOMA-IR: 1.86 +/- 0.35), insulin resistance was greater in HA-Pla (3.00 /- 0.45; P < 0.05), SL-Prz (3.46 +/- 0.51; P < 0.01), and HA-Prz (2.82 +/- 0.43; P < 0.05). Insulin sensitivity was reduced in HA-Pla (C-ISI: 4.41 +/- 1.03; P < 0.01), SL-Prz (5.73 +/- 1.01; P < 0.05), and HA-Prz (4.18 +/- 0. 99; P < 0.01) relative to SL-Pla (8.02 +/- 0.92). Plasma epinephrine was si gnificantly elevated in HA-Pla (0.57 +/- 0.08 ng/ml; P < 0.01), SL-Prz (0.4 2 +/- 0.07; P < 0.05), and HA-Prz (0.82 +/- 0.07; P < 0.01) relative to SL- Pla (0.28 +/- 0.04), but correlations with HOMA- IR, HOMA-<beta>-cell funct ion, and C-ISI were weak. In women, short-term exposure to simulated HA red uced insulin sensitivity compared with SL. The change does not appear to be directly mediated by a concurrent rise in plasma epinephrine concentration s.