In this report we provide evidence from cell culture, murine and human studies that IH in OSA contributes independently to the development of IR. We also demonstrate for the first time that IH induces obesity-like morphological pro-inflammatory changes in adipose tissue, which correlate with IR in lean and obese mice and may contribute to the pathogenesis of IR in patients with OSA.
The results of our study are in keeping with previous reports supporting an independent association of OSA with IR. These findings are strengthened by the exclusion of subjects with significant confounding comorbidities, and the recruitment of participants across the spectrum of weight categories. We believe that the lack of statistical significance in HOMA-IR between OSA and controls in group 3 is due to the low number of controls, subjects which are especially difficult to recruit; overall, our data indicate that OSA impacts on IR independently of the degree of obesity.
The pivotal role of IH in the underlying pathogenesis is supported by the mouse experiments demonstrating diminished insulin sensitivity with IH. Previous studies have mainly been performed in lean mice. DRAGER et al. also reported impaired insulin sensitivity in diet-induced obese mice using the HOMA-IR index as a surrogate marker that remained unaffected by IH in our experiments. This parameter reflects the balance between hepatic glucose output and insulin secretion, which is maintained by a feedback loop between the liver and β-cells, unlike the ITT, which also assesses the peripheral insulin sensitivity of the target tissues, i.e. adipose tissue and skeletal muscle. In rodents, the HOMA-IR index is less sensitive to changes in insulin sensitivity and whereas DRAGER et al. measured fasting glucose and insulin directly after cessation of IH, we performed these measurements after overnight cessation of the stimulus, which may explain the discrepancy between the two studies.
Comments