The effect of long-term exposure to moderate high altitude on adipokines and insulin sensitivity.

Abstract

Background: High altitude area refers to plateau area with an altitude of 1500 m or above. Short-term (less than 30 days) exposure to high-altitude environments (hypoxia, low temperature, low pressure) might affect the adipokines level and insulin sensitivity. However, whether long-term exposure to moderate high altitude would have an impact on adipokines and insulin sensitivity remains unknown.

Objective: This study aimed to explore the effect of long-term exposure (12 months) to moderate high altitudes (2900 m) on changes in adipokines level and insulin sensitivity.

Methods: 48 healthy adults from Guangdong Province (the average altitude less than 50 m) to Nyingchi (an average altitude of 2900 m) were included with follow-up of 12 months. Before entering Nyingchi, baseline anthropometric indicators (height, weight, blood pressure), metabolic indicators: fasting plasma glucose (FPG), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), insulin resistance index (HOMA-IR), adipokines: adiponectin and leptin, inflammatory indicators: tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6); hypoxia-inducible factor 1alpha (HIF-1α), oxidative stress indicator: malondialdehyde (MDA), antioxidant indicators: superoxide dismutase (SOD) and glutathione (GSH) were determined. After entering Nyingchi, the above indicators were retested at the 1st, 6th, and 12th month. The control group consist of 47 local residents in Nyingchi. Linear mixed effect model was used to analyze the trend of index changes. Multivariate linear regression analysis was analyzed to explore the influence factors of adiponectin at 12th month.

Results: After 12 months exposure to high altitude, the body mass index (BMI), systolic blood pressure (SBP) and FPG of subjects decreased from baseline of 23.51 ± 2.68 kg/m², 123.68 ± 14.94 mmHg and 5.05 ± 0.36 mmol/L to 22.59 ± 2.56 kg/m², 116.10 ± 14.68 mmHg and 4.65 ± 0.46 mmol/L respectively, HDL-C increased from baseline of 1.30 ± 0.26 mmol/L to 1.37 ± 0.30 mmol/L. HOMA-IR decreased from baseline 1.70 (1.19, 2.22) to 1.25(1.04, 1.78). Adiponectin increased from 3.85(3.05, 4.98) to 4.75(3.33, 5.88) μg/mL, leptin decreased from 1022.10(496.30, 2508.60) to 729.60(308.78, 1670.20) pg/mL. TNFα decreased from 6.81(5.37, 8.49) to 5.50(4.00, 6.74) pg/mL. The level of HIF-1α increased from baseline 1.91 (1.32, 5.09) to 2.94 (1.65, 15.45) pg/mL. SOD increased from 0.20(0.15, 0.24) to 0.25(0.20, 0.28) U/mL. Multivariate linear regression analysis showed that HIF-1α (β = 0.006, 95 %CI, 0.001-0.012, p = 0.033) and SOD (β = 7.318, 95 %CI, 0.486-14.149, p = 0.037) was the factors that influenced adiponectin level at 12th month after exposure to high altitude.

Conclusion: Long-term exposure to moderate high-altitude environments could improve insulin sensitivity and adipocyte function in healthy adults. Elevated HIF-1α and SOD during altitude acclimatization were the beneficial factors for improvement of adipocyte function. It is worthwhile to further explore the effect and the potential therapeutic value of long-term moderate altitude exposure on adults with metabolic disorders.