title: Women at altitude: short-term exposure to hypoxia and/or alpha(1)-adrenergic blockade reduces insulin sensitivity.
abstract: After short-term exposure to high altitude (HA), men appear to be less sensitive to insulin than at sea level (SL). We hypothesized that the same would be true in women, that reduced insulin sensitivity would be directly related 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 and after 16 h at simulated 4,300-m elevation (HA). Subjects were studied twice at each elevation: once with prazosin (Prz), an alpha(1)-adrenergic antagonist, and once with placebo (Pla). Mathematical models were used to assess insulin resistance based on fasting [homeostasis model assessment of insulin resistance (HOMA-IR)] and postprandial [composite model insulin sensitivity 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 significantly elevated in HA-Pla (0.57 +/- 0.08 ng/ml; P < 0.01), SL-Prz (0.42 +/- 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 function, and C-ISI were weak. In women, short-term exposure to simulated HA reduced insulin sensitivity compared with SL. The change does not appear to be directly mediated by a concurrent rise in plasma epinephrine concentrations.
authors.affiliation: Geriatric Research, Education and Clinical Center, Veterans Affairs Health Care System, Stanford University School of Medicine, Palo Alto, California 94304, USA. bbraun@exsci.umass.edu
authors.forename: B
authors.initials: B
authors.lastname: Braun
authors.forename: P B
authors.initials: PB
authors.lastname: Rock
authors.forename: S
authors.initials: S
authors.lastname: Zamudio
authors.forename: G E
authors.initials: GE
authors.lastname: Wolfel
authors.forename: R S
authors.initials: RS
authors.lastname: Mazzeo
authors.forename: S R
authors.initials: SR
authors.lastname: Muza
authors.forename: C S
authors.initials: CS
authors.lastname: Fulco
authors.forename: L G
authors.initials: LG
authors.lastname: Moore
authors.forename: G E
authors.initials: GE
authors.lastname: Butterfield
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000328:Adult; D000531:Altitude; D000532:Altitude Sickness / Q000097:blood / Q000503:physiopathology*; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D004040:Dietary Carbohydrates; D004837:Epinephrine / Q000494:pharmacology; D005215:Fasting; D005260:Female; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D008297:Male; D008954:Models, Biological; D010919:Placebos; D011224:Prazosin / Q000494:pharmacology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D012016:Reference Values; D012727:Sex Characteristics; D013997:Time Factors
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D001786:Blood Glucose; D002096:C-Peptide; D004040:Dietary Carbohydrates; D007328:Insulin; D010919:Placebos; D018340:Receptors, Adrenergic, alpha-1; D011224:Prazosin; D004837:Epinephrine