Independent association of vitamin D and insulin resistance in obstructive sleep apnea

Abstract

Background: Vitamin D insufficiency and/or high levels of parathyroid hormone (PTH) seem to be associated with abnormal glucose metabolism, which is frequent in obstructive sleep apnea (OSA). The purpose of this study was to investigate vitamin D and PTH concentrations in OSA, and to explore potential links between vitamin D, PTH and insulin resistance (IR).

Methods: A total of 112 subjects with suspected OSA were recruited consecutively, and evaluated by polysomnography (PSG) to determine the number of apnea and hypopnea episodes per hour of sleep (apnea/hypopnea index: AHI). OSA was diagnosed for AHI≥5. Average (APO2) and minimum pulse oxygen saturation (MPO2) were assessed during PSG as indices of nocturnal hypoxemia. After overnight fasting, a standard 75g oral glucose tolerance test was performed. Serum 25-hydroxyvitamin D, PTH, fasting glucose and fasting insulin were also measured. Homeostasis model assessment (HOMA) was used to evaluate IR: HOMA-IR=fasting plasma insulin×fasting plasma glucose/22.5, with "insulin resistance" defined as HOMA-IR>2.7.

Results: Patients were classified into 4 groups according to AHI: control group (AHI<5, n=8), mild OSA (5≤AHI<15, n=18), moderate OSA (15≤AHI<30, n=33), and severe OSA (AHI≥30, n=53). They were also classified, according to HOMA-IR, as insulin-resistant (HOMA-IR>2.7, n=59) or non-insulin-resistant (HOMA-IR≤2.7, n=45). There were no significant differences in vitamin D or PTH levels between AHI groups. HOMA-IR was significantly higher in severe OSA than in controls (P=0.019). Vitamin D concentration correlated negatively with AHI (r=-0.242, P=0.01) and with HOMA-IR (r=-0.338, P<0.001). PTH concentration correlated negatively with vitamin D concentration (P<0.001), but not with AHI or HOMA-IR. HOMA-IR correlated positively with AHI (r=0.368, P<0.001) and negatively with MPO2 (r=-0.414, P<0.001). Finally, stepwise linear multivariate regression showed that vitamin D concentration (β=-0.209, P=0.014) and MPO2 (β=-0.221, P=0.011) were independently associated with HOMA-IR.

Conclusion: Subjects with severe OSA may have a low vitamin D level associated with increased risk of IR. Vitamin D was independently associated with IR in OSA. Vitamin D insufficiency may play a role in the pathogenesis of IR in OSA.

Keywords: Apnée obstructive du sommeil; Hormone parathyroïdienne; Insulin resistance; Obstructive sleep apnea; Parathyroid hormone; Résistance à l’insuline; Vitamine D; Vitamin D.