Autonomic dysfunction in obstructive sleep apnea is associated with impaired glucose regulation

Abstract

Introduction

Autonomic dysfunction has been theorized to be responsible for the increased risk of cardiovascular disease in obstructive sleep apnea (OSA). Previous studies did not control for the presence of impaired glucose regulation (IGR, comprising impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes) which is also associated with abnormalities in autonomic function.

Methods

Thirty-two patients were recruited for the study. Patients underwent autonomic testing consisting of heart rate response to deep breathing, valsalva maneuver, tilt-up, and quantitative sudomotor axon reflex testing. Polysomnography (PSG) and a 2-h oral glucose tolerance test were performed. Results were analyzed with logistic regression, with age, race, body mass index (BMI), and gender as covariates.

Results

Nineteen of 24 patients with OSA had abnormal glucose (79%, p = 0.04) compared to two of nine patients without OSA. The correlation between IGR, OSA and total autonomic dysfunction was similar (p = .10 for IGR, p = 0.06 for OSA). However, cardiac autonomic function was more strongly associated with IGR than OSA (p = .10 vs. 0.50). Age was a significant confounder, as glucose correlated with adrenergic autonomic dysfunction significantly when age was removed from the model (p = 0.006).

Conclusions

The presence of IGR may be a confounding factor in studies of autonomic function in OSA. Larger studies are needed to delineate whether OSA is directly associated with autonomic dysfunction or whether the previously described association between dysautonomia and OSA may have been due to glucose dysregulation.

Introduction

Obstructive sleep apnea (OSA) affects approximately 2–4% of the United States population [1]. The increased risk in cardiovascular disease in OSA has been attributed to hyperactivity of the adrenergic system, caused by chronic intermittent hypoxia. Animal models of recurrent hypoxia have demonstrated sustained hypertension and increased neuronal activity in brainstem nuclei involved in regulating sympathetic nerve activity [2], [3]. Multiple previous studies have demonstrated abnormalities in cardiac adrenergic function in patients with OSA, supporting this hypothesis [1], [4], [5], [6], [7], [8]. In addition, several studies evaluating vagal cardiac activity have found abnormalities in vagal function as well [2], [6], [9], [10].

OSA is tightly associated with the metabolic syndrome and diabetes mellitus [11], [12], [13]. In one study, 40% of subjects with OSA had impaired fasting glucose (IFG), and another 12% had undiagnosed diabetes [13]. Autonomic dysfunction in diabetes was once thought to be a late complication of the disorder, particularly in type II diabetics. However, recent literature suggests that autonomic dysfunction occurs early, and can be abnormal in subjects with prediabetes (IFG or impaired glucose tolerance (IGT)) [14], [15], [16], [17].

Previous studies evaluating autonomic function in OSA either did not test for impaired glucose regulation (IGR) or relied upon older criteria for fasting plasma glucose which changed in 2003 [18]. Therefore, it is not known whether changes in autonomic function observed in OSA are a direct result of OSA or have been observed because of the high prevalence of undiagnosed IGR in subjects with OSA.

This clinical study evaluates the association between IGR, OSA, and autonomic function.