Sympathetic overactivity caused by chronic intermittent hypoxia (CIH) is a landmark of obstructive sleep apnoea (OSA). A high sympathetic tone elicits rises in plasma free fatty acid (FFA) and insulin. Our objective was to assess the impact of 14 nights of CIH exposure on sympathetic activity, glucose control, lipid profile and subcutaneous fat tissue remodelling in non-obese healthy humans.

In this prospective, double-blinded cross-over study, 12 healthy subjects were selected, in those only 9 underwent the 2 phases of exposures of 14 nights randomized to CIH vs. air. Sympathetic activity was measured by peroneal microneurography (MSNA) before and after each exposure. Fasting glucose, insulin, c-peptide and FFAs were assessed at rest and during a multisampling oral glucose tolerance test (OGTT). We assessed histological remodelling, adrenergic receptors, lipolysis and lipogenesis genes expression and functional changes of the adipose tissue.

CIH significantly increase sympathetic tone, p=0.04, compared to room air. MSNA in burst/min went for room air, from 24.5 [18.9;26.8] to 21.7 [13.8;25.7] and for intermittent hypoxia, from 20.6 [17.4;23.9] to 28.0 [24.4;31.5]. Circulating FFA increased after OGTT, area under the curve p=0.05 and the FFAs sensitivity to insulin decreased, p=0.028. In adipocyte tissue, IH increased expression of lipolysis genes (ATGL and HSL) and lipogenesis genes (Fatty Acid Synthase), p<0.05 for al.

In this unique experimental setting in healthy humans, CIH induced high sympathetic tone and a decreased FFAs sensitivity to insulin. This might participate in OSA patient?s trajectory to systemic insulin resistance and diabetes.