The Rise of IGFBP4 in People with Obstructive Sleep Apnea and Multilevel Sleep Surgery Recovers Its Basal Levels

Abstract

IGFBP4 is the smallest member of the insulin-like growth factor binding protein family (IGFBP). It is a hepatic protein that plays a role in modulating the activity and bioavailability of IGF-I. The expression of IGFBP4 was found to increase under conditions of hypoxia. Obstructive sleep apnea (OSA) is a common disorder, characterized by cyclic episodes of intermittent hypoxia and fragmented sleep. Our aim was to quantify levels of circulating IGFBP1, IGFBP2, IGFBP3, IGFBP4, and IGFBP7 in fasting plasma samples of 69 Kuwaiti participants and explore its correlation with indices of OSA. The quantification was performed using multiplexing assay. The study involved 28 controls and 41 patients with OSA. Levels of circulating IGFBP4 were significantly higher in people with OSA ( $289.74\pm 23.30$  ng/ml) compared to the control group ( $217.60\pm 21.74$  ng/ml, $p=0.028$ ). The increase in IGFBP4 correlated significantly and positively with AHI ( $r=.574$ , $p=.01$ ) and AI ( $r=.794$ , $p=.001$ ) in people with moderate and severe OSA. There was a significant decline in circulating IGFBP4 after 3 months of surgery ( $225.89\pm 18.16$  ng/ml, $p=0.012$ ). This was accompanied by a prominent improvement in OSA (AHI $8.97\pm 2.37$ events/h, $p=0.001$ ). In this study, our data showed a significant increase in circulating IGFBP4 in people with OSA. We also report a significant positive correlation between IGFBP4 and indices of OSA at baseline, which suggests IGFBP4 as a potential diagnostic biomarker for OSA. There was a significant improvement in OSA after 3 months of surgical intervention, which concurred with a significant decline in IGFBP4 levels. Altogether, the detected change suggests a potential link between IGFBP4 and OSA or an OSA-related factor, whereby OSA might play a role in triggering the induction of IGFBP4 expression.