Rationale: Obstructive sleep apnea (OSA), a treatable sleep disorder that is associated with alterations in glucose metabolism in individuals without diabetes, is a highly prevalent comorbidity of type 2 diabetes. However, it is not known whether the severity of OSA is a predictor of glycemic control in patients with diabetes. Objectives: To determine the impact of OSA on hemoglobin A1c (HbA1c), the major clinical indicator of glycemic control, in patients with type 2 diabetes. Methods: We performed polysomnography studies and measured HbA1c in 60 consecutive patients with diabetes recruited from outpatient clinics between February 2007 and August 2009. Measurements and Main Results: A total of 77% of patients with diabetes had OSA (apnea-hypopnea index [AHI] >5). Increasing OSA severity was associated with poorer glucose control, after controlling for age, sex, race, body mass index, number of diabetes medications, level of exercise, years of diabetes and total sleep time. Compared with patients without OSA, the adjusted mean HbA1c was increased by 1.49% (P 5 0.0028) in patients with mild OSA, 1.93% (P 5 0.0033) in patients with moderate OSA, and 3.69% (P , 0.0001) in patients with severe OSA (P , 0.0001 for linear trend). Measures of OSA severity, including total AHI (P 5 0.004), rapid eye movement AHI (P 5 0.005), and the oxygen desaturation index during total and rapid eye movement sleep (P 5 0.005 and P 5 0.008, respectively) were positively correlated with increasing HbA1c levels. Conclusions: In patients with type 2 diabetes, increasing severity of OSA is associated with poorer glucose control, independent of adiposity and other confounders, with effect sizes comparable to those of widely used hypoglycemic drugs.

OSA is a treatable sleep disorder that is pervasive among overweight and obese individuals. Current evidence supports a robust association between OSA and insulin resistance, glucose intolerance and the risk of type 2 diabetes, independent of obesity. Up to 83% of patients with type 2 diabetes suffer from unrecognized OSA and increasing severity of OSA is independently associated with poorer glucose control. Evidence from animal and human models that mimic OSA supports a potential causal role for OSA in altered glucose metabolism. Robust prospective and randomized clinical trials are still needed to test the hypothesis that effective treatment of OSA may prevent the development of type 2 diabetes and its complications, or reduce its severity. Type 2 diabetes is occurring at alarming rates worldwide and despite available treatment options, the economic and public health burden of this epidemic remains enormous. OSA might represent a novel, modifiable risk factor for the development of prediabetes and type 2 diabetes. KeywordsObstructive sleep apnea; diabetes; prediabetes; glucose tolerance; insulin resistance; CPAP; cardiovascular; metabolic; glycemic control Obstructive sleep apnea (OSA) is a chronic sleep disorder, affecting 24% of men and 9% of women in the general population [1]. OSA prevalence appears to increase steadily with advancing age and men are at 2-3 fold greater risk for OSA compared to women [2]. Notably, OSA is pervasive among overweight and obese individuals, who represent about two thirds of the U.S. adult population today. Recent estimates of the prevalence of OSA in obese adults aged 30 to 69 years have ranged from 11 to 46% in women and 33 to 77% in men [3]. In longitudinal analyses, weight gain predicts increased OSA incidence and severity [4] [5].Despite the demonstrated efficacy of lifestyle interventions and the availability of multiple pharmacological treatment options, the economic and public health burden of diabetes remains enormous [6]. Prediabetes is defined by elevated glucose levels not sufficient to meet the diagnostic criteria for diabetes. Specifically, prediabetes refers to either impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) in response to oral glucose [7]. Both IFG and IGT represent an insulin resistant state and are major risk factors for Address for correspondence and requests for reprints: Sushmita Pamidi, M.D., Department of Medicine MC 4000, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, Tel: (773) 702-0986, spamidi@medicine.bsd.uchicago.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the ...

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