Association Between Intermittent Hypoxia and Systemic Inflammation in Obese Patients With Obstructive Sleep Apnea: Mediating Role of HIF-1α and Metabolic Predictors

Background and Objective Obstructive sleep apnea (OSA) in obese individuals is associated with systemic inflammation, but the contribution of intermittent hypoxia and hypoxia-inducible factor-1α (HIF-1α) in Indian populations remains unclear. This study examined whether intermittent hypoxia is independently associated with inflammation via HIF-1α in obese adults with OSA.Methods This hospital-based case–control study included 90 obese adults (body mass index [BMI] ≥30 kg/m²): 45 with OSA (apnea-hypopnea index [AHI] ≥5 events/h) and 45 BMI- and age-matched controls (AHI <5 events/h). Polysomnography assessed AHI, oxygen desaturation index (ODI), and SpO₂. Fasting serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and HIF-1α were measured using ELISA, and insulin resistance was estimated by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Group comparisons used t-tests or Mann–Whitney U tests with Bonferroni correction (p<0.003). Multiple regression adjusted for age, BMI, and sex identified predictors, and bootstrapped mediation (5,000 resamples) evaluated HIF-1α mediation between ODI and inflammation.Results The OSA group had higher ODI, lower SpO₂, and elevated HOMA-IR, cholesterol, creatinine, and inflammatory markers (IL-6, CRP, TNF-α, and HIF-1α; all p<0.001). ODI was the strongest predictor of IL-6 (β=0.55), CRP (β=0.40), TNF-α (β=0.67), and HIF-1α (β=0.62; all p≤0.001). HIF-1α partially mediated ODI–inflammation associations.Conclusions Intermittent hypoxia appears to be associated with systemic inflammation in obese adults with OSA via HIF-1α activation, independent of obesity. ODI appeared to be a strong marker of intermittent hypoxic burden; however, it does not capture the duration of hypoxemia, which may be better reflected by indices such as T90.