Abstract
BackgroundNotwithstanding previous studies supporting independent associations between obstructive sleep apnea (OSA) and prevalence of diabetes, the underlying pathogenesis of impaired glucose regulation in OSA remains unclear. We explored mechanisms linking OSA with prediabetes/diabetes and associated biomarker profiles. We hypothesized that OSA is associated with distinct alterations in glucose homeostasis and biomarker profiles in subjects with normal (NGM) and impaired glucose metabolism (IGM).MethodsForty-five severely obese adults (36 women) without certain comorbidities/medications underwent anthropometric measurements, polysomnography, and blood tests. We measured fasting serum glucose, insulin, selected cytokines, and calculated homeostasis model assessment estimates of insulin sensitivity (HOMA-IS) and pancreatic beta-cell function (HOMA-B).ResultsBoth increases in apnea-hypopnea index (AHI) and the presence of prediabetes/diabetes were associated with reductions in HOMA-IS in the entire cohort even after adjustment for sex, race, age, and BMI (P = 0.003). In subjects with NGM (n = 30), OSA severity was associated with significantly increased HOMA-B (a trend towards decreased HOMA-IS) independent of sex and adiposity. OSA-related oxyhemoglobin desaturations correlated with TNF-α (r=-0.76; P = 0.001) in women with NGM and with IL-6 (rho=-0.55; P = 0.035) in women with IGM (n = 15) matched individually for age, adiposity, and AHI.ConclusionsOSA is independently associated with altered glucose homeostasis and increased basal beta-cell function in severely obese adults with NGM. The findings suggest that moderate to severe OSA imposes an excessive functional demand on pancreatic beta-cells, which may lead to their exhaustion and impaired secretory capacity over time. The two distinct biomarker profiles linking sleep apnea with NGM and IGM via TNF-α and IL-6 have been discerned in our study to suggest that sleep apnea and particularly nocturnal oxyhemoglobin desaturations are associated with chronic metabolic fluxes and specific cytokine stressors that reflect links between sleep apnea and glucose metabolism. The study may help illuminate potential mechanisms for glucose dysregulation in OSA, and resolve some controversy over the associations of OSA with TNF-α and IL-6 in previous studies.
Highlights
Obstructive sleep apnea (OSA) and impaired glucose metabolism (IGM) are closely linked to an epidemic of obesity in Western society, and both are associated with a significantly increased cardiovascular risk
The obstructive sleep apnea (OSA) severity was associated with male sex, central adiposity, and with alterations in glucose homeostasis
In a model adjusting for sex, race, age, and body mass index (BMI), both increases in apnea-hypopnea index (AHI) and the presence of prediabetes/diabetes were associated with reductions in homeostasis model assessment estimates of insulin sensitivity (HOMA-IS) (P = 0.003) in the entire cohort
Summary
Obstructive sleep apnea (OSA) and impaired glucose metabolism (IGM) are closely linked to an epidemic of obesity in Western society, and both are associated with a significantly increased cardiovascular risk. Epidemiologic data from the Sleep Heart Health Study [1] suggested that OSA is associated with glucose intolerance and insulin resistance independent of obesity, and may lead to type 2 diabetes mellitus. The underlying mechanisms for IGM in OSA and obesity remain less well understood Both increases in insulin resistance and decline in betacell function play a role in the development of prediabetes and subsequent type 2 diabetes [2]. Notwithstanding previous studies supporting independent associations between obstructive sleep apnea (OSA) and prevalence of diabetes, the underlying pathogenesis of impaired glucose regulation in OSA remains unclear. We hypothesized that OSA is associated with distinct alterations in glucose homeostasis and biomarker profiles in subjects with normal (NGM) and impaired glucose metabolism (IGM)
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