High-Altitude Exposure Is Associated with Sustained Inflammation and Hyperinsulinemia in Healthy Individuals: An Investigative Study on Human Expedition

This study aimed to investigate the integrated in vivo impact of progressive high altitude on metabolic, inflammatory, and vascular adaptation pathways and to assess their modulation by biological sex and anthropometric profile. A Himalayan expedition was conducted with fifteen volunteers (nine men, six women; age 43 ± 15 years; body mass index (BMI) of 24.2 ± 3.70 kg/m2). Participants received acetazolamide (250 mg/day). Blood samples were collected before (50 m above sea level), during (1400 m and 5000 m), and after the Himalayan trip (return to 1400 m). Serum concentrations of Adipocyte Complement-Related Protein of 30 kDa (Adiponectin/Acrp30), C-Reactive Protein (CRP), Plasminogen Activator Inhibitor-1 (Serpin E1/PAI-1), Monocyte Chemoattractant Protein-1/chemokine (C-C motif) ligand 2 (MCP-1/CCL2), basic Fibroblast Growth Factor (bFGF), Insulin, Leptin, Macrophage Migration Inhibitory Factor (MIF) and Tumor Necrosis Factor alpha (TNF-α) were measured. Progressive exposure to high altitude induced significant activation of inflammatory pathways, documented by progressively increased serum levels, compared to baseline, of CRP, MCP-1, PAI-1, and TNF-α (all p < 0.05). Insulin increased significantly at maximum altitude (p = 0.032), with persistence during descent (p = 0.042). bFGF showed a biphasic trend. Leptin, adiponectin, and MIF changes did not reach statistical significance. A mixed repeated-measures ANOVA confirmed a significant main effect of altitude on insulin concentration (p = 0.005), on CRP (p = 0.009), on MCP-1 (p = 0.004), and on TNF-α levels (p < 0.001). However, no significant interaction of sex and BMI (Body Mass Index) with altitude was observed. Elevated CRP, MCP-1, PAI-1, and TNF-α persisted during descent, suggesting delayed resolution of the high-altitude-induced inflammatory response. These results show that progressive high altitude induces systemic inflammation and hyperinsulinemia, which persist during descent, providing new insights into the relationship between altitude-induced inflammatory pathways and insulin dynamics.