ATS 2012, SAN FRANCISCO –The severity of sleep disordered breathing and nocturnal hypoxemia independently predict both glycosylated hemoglobin (HbA1c) levels and type 2 diabetes mellitus (T2DM), according to a new study.
"Because people with obstructive sleep apnea syndrome (OSAS) are often overweight or obese it has been difficult to interpret earlier studies of the relationship between sleep disordered breathing and metabolic disorders," said Brian Kent, MBBCh, research fellow at St. Vincent's University Hospital in Dublin. "We found that obstructive sleep apnea syndrome (OSAS) severity and low nocturnal oxygen levels were significant independent predictors of prevalent T2DM and HbA1c levels, even after adjustment for a number of confounding variables, including obesity."
The research will be presented at the ATS 2012 International Conference in San Francisco.
The study involved 7,886 prospectively assessed subjects from 22 sleep laboratories in 16 European countries. All subjects completed overnight sleep studies.
After adjustment for comorbidities and demographic and anthropometric variables, moderate and severe OSAS were each significant (P=.003) predictors of having a diagnosis of T2DM. Apnea/hypopnea index, oxyhemoglobin desaturation index, and mean oxygen saturation (SpO2) were significant (P<.0001) predictors of HbA1c levels.
"A diagnosis of T2DM is associated with a significantly increased risk of cardiovascular morbidity and death, and elevated HbA1c levels predict cardiovascular mortality in non-diabetic subjects," said Dr. Kent. "OSAS has also been shown to be associated with adverse cardio-metabolic outcomes, although whether OSAS independently predicts these outcomes is not clear."
"Our study shows that OSAS is independently associated with metabolic disturbances," said Dr. Kent. "This is important because individuals with T2DM or elevated HbA1c levels are more likely to die of cardiovascular disease."
"Further detailed studies are needed to understand the mechanism underlying this relationship in people with OSAS."
"Severity Of Sleep Disordered Breathing Is An Independent Predictor Of Glycemic Health: The European Sleep Cohort (ESADA) Study" (Session D18, Wednesday, May 23, 10:15 a.m., Room 3020-3022, Moscone Center; Abstract 27667)
* Please note that numbers in this release may differ slightly from those in the abstract. Many of these investigations are ongoing; the release represents the most up-to-date data available at press time.
Abstract 27667
Severity Of Sleep Disordered Breathing Is An Independent Predictor Of Glycemic Health: The European Sleep Cohort (ESADA) Study
Type: Scientific Abstract
Category: 16.02 - Sleep Disordered Breathing: Cardiovascular and Neuroendocrine Interactions (SRN)
Authors: B.D. Kent1, L. Grote2, M. Bonsignore3, T. Saaresranta4, J. Verbraecken5, P.A. Levy6, P. Sliwinski7, R. Tkacova8, J.-A. Kvamme9, J. Hedner2, W.T. McNicholas1; 1St. Vincent's University Hospital - Dublin/IE, 2Sahlgrenska University Hospital - Gothenburg/SE, 3CNR Institute of Biomedicine and Molecular Immunology - Palermo/IT, 4Turku University Central Hospital Paimio - Preitila/FI, 5University Hospital Antwerp - Antwerp/BE, 6Joseph Fourier University and Grenoble University Hospital - Grenoble/FR, 7Institute of Tuberculosis and Lung Diseases - Warsaw/PL, 8P.J. Safarik University and L. Pasteur University Hospital - Kosice/SK, 9Førde Central Hospital - Forde/NO; On behalf of the European Sleep Cohort (ESADA) Study Group
Rationale
A diagnosis of diabetes mellitus (T2DM) is predictive of a substantially increased risk of premature cardiovascular morbidity and death, while glycosylated hemoglobin (HbA1c) has recently been identified as a robust predictor of subsequent cardiovascular mortality in non-diabetic populations. Obstructive sleep apnea syndrome (OSAS) is a highly prevalent disorder strongly associated with adverse cardio-metabolic outcomes. However, obesity is a major confounding factor in studies of subjects with sleep disordered breathing, and the role of OSAS as an independent driver of metabolic disease remains uncertain. We sought to examine the relationship of OSAS severity with T2DM prevalence and HbA1c levels in a large, multicenter, multinational population.
Methods
Subjects attending 22 university-affiliated sleep laboratories across 16 European countries were prospectively assessed. All subjects underwent overnight sleep studies, and had blood samples drawn to assess glycemic health. Multivariate logistic regression was performed to assess the relationship of OSAS severity with T2DM prevalence, while separate multivariate linear regression analyses were used to examine the influence of OSAS severity indices on HbA1c levels in the whole population and in non-diabetic subjects. All analyses were adjusted for demographic factors, obesity measures, co-morbidities and medication use.
Results
A total of 7,886 subjects were assessed. 71.6% were male, 50.8% were obese, and 80.3% had an apnoea-hypopnea index (AHI) >5 events/hour. In unadjusted analysis, clinician-diagnosed T2DM prevalence was significantly higher in those with mild, moderate, and severe OSAS than in non-OSAS subjects. Following adjustment for demographic, anthropometric, and co-morbid variables, moderate (adjusted odds ratio (AOR) 1.54; 95% CI 1.16-2.04; p=0.003) and severe OSAS (AOR 1.51; 95% CI 1.15-1.98; p=0.003) remained significant predictors of a diagnosis of T2DM. In bivariate analysis HbA1c correlated significantly with AHI in the overall population (r=0.225; p<0.0001), and particularly in non-diabetic patients (r=0.258; p<0.0001). A similar relationship was observed with the oxyhemoglobin desaturation index (ODI). Nocturnal hypoxemia, as measured by mean nocturnal SpO2, had the strongest relationship with HbA1c (r=-0.274; p<0.0001). Following adjustment for confounding variables, AHI (standardized Β 0.101; p<0.0001), ODI (standardized Β 0.082;p<0.0001) and mean SpO2 (standardized Β -0.119; p<0.0001) remained significant predictors of HbA1c levels.
Conclusions
OSAS severity and nocturnal hypoxemia are independent predictors of both prevalent T2DM and HbA1c levels. This relationship persists following rigorous adjustment for confounding variables such as obesity measures, medication use and comorbid illness. Further mechanistic studies are required to explore the interaction between OSAS, obese adipose tissue function and metabolic health.
Funded by: Health Research Board, Ireland