Women at altitude: short-term exposure to hypoxia and/or α₁-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.

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].…”

“…However, in a case study, a patient with type 1 diabetes found increased fasting glucose levels of 60% despite maintaining caloric intake [16]. The increase in blood glucose level was reported to be gender specific, with females affected more than males [11,17]. Impaired blood glucose regulation occurred when hypoxic training was performed with high intensive training of incremental durations of maximal aerobic power and ventilatory threshold [12], whereas with moderate intensity of exercise, glucose tolerance and insulin sensitivity depended on level of altitude where moderate levels produced increased glucose metabolism [6] while higher altitude (>3,000m) resulted in impairment in blood glucose regulations [10,11,16].…”

“…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].…”

Endocrine and metabolic responses to extreme altitude and physical exercise in climbers

“…The acute exposure to reduced partial pressure of oxygen at HA decreases arterial oxygen saturation, stimulates the sympathoadrenal system, and provokes shifts in substrate metabolism (2)(3)(4)(5). Indeed, the response to HA in terms of energy utilization has been deeply investigated (2,(6)(7)(8)(9)(10)(11) but data about endocrine adaptations are scanty and discrepant, likely reflecting different experimental models and wide relative ranges of altitudes, and generally investigating the short-term endocrine response only.…”

Cortisol, resposta glicêmica e secreção de insulina em equinos clinicamente sadios submetidos a sessões de hipóxia normobárica

“…Entretanto, os resultados publicados até o momento ainda são inconsistentes. Isso provavelmente ocorre pela diversidade entre espécies, grau e duração da hipóxia ou como consequência da complexidade dos mecanismos regulatórios do metabolismo (CHEN et al, 2007 Estudos em diversas espécies demonstraram que a exposição a diferentes condições de hipóxia pode causar aumento da resistência à insulina (CHENG et al, 1997;BRAUN et al, 2001;POLOTSKY et al, 2003;IIYORI et al, 2007). Um dos hormônios capazes de causar tal efeito é o cortisol (ANDREWS & WALKER, 1999), que pode estar com seus níveis circulantes aumentados quando da exposição aguda ou crônica de indivíduos a baixas concentrações de oxigênio ([O2]) (HUMPELER et al, 1980;COSTE et al, 2005).…”