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      Sleep apnea predicts distinct alterations in glucose homeostasis and biomarkers in obese adults with normal and impaired glucose metabolism

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          Abstract

          Background

          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 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).

          Methods

          Forty-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).

          Results

          Both 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.

          Conclusions

          OSA 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.

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          Most cited references 28

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          Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force.

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                Author and article information

                Journal
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central
                1475-2840
                2010
                1 December 2010
                : 9
                : 83
                Affiliations
                [1 ]Johns Hopkins Sleep Disorders Center, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA
                [2 ]Department of Physiology and Sleep Laboratory, PJ Safarik University School of Medicine, Kosice, Slovakia
                [3 ]Bariatric Surgery Program, Department of Surgery, Johns Hopkins Bayview Medical Center, Baltimore, MD, USA
                [4 ]Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Churchill Hospital, Oxford, UK
                Article
                1475-2840-9-83
                10.1186/1475-2840-9-83
                3002325
                21122092
                Copyright ©2010 Pallayova et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<url>http://creativecommons.org/licenses/by/2.0</url>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Original Investigation

                Endocrinology & Diabetes

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