Obstructive Sleep Apnea and Type 2 Diabetes Mellitus: Examining the Evidence

Type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) are two common, chronic conditions that are associated with both prevalent and incident cardiac disease. Although T2DM and OSA share a common risk factor, i.e. obesity, accruing evidence over the last two decades has demonstrated that there is an independent association between OSA and T2DM. Estimates on the prevalence of OSA in type 2 diabetics are indeed staggering with studies showing that well over 50% of type 2 diabetics have OSA.1-3 Initial studies demonstrated a cross-sectional association between self-reported OSA and glucose disorders but had methodological limitations such as lack of objective assessment of sleep-disordered breathing and the absence of adjustment for important confounders such as obesity and sleep duration. Thus, interpretation of the findings from these studies was challenging. However, subsequent studies were more rigorous in their approach and included polysomnographic-derived metrics of sleep apnea, addressed confounding, and provided longitudinal data. These latter investigations confirmed an independent association between OSA and glucose disorders.4,5

Mechanistic pathways linking OSA to glucose dysregulation are less well elucidated and are being explored. The concurrence of experimental data from both animal and human studies suggest that intermittent hypoxia and recurrent arousals from sleep, the two pathophysiological concomitants of OSA, are likely to mediate the disruption in glucose homeostasis observed in OSA. However, downstream pathways that could connect intermittent hypoxia and sleep fragmentation to metabolic dysfunction are not well delineated. Potential mechanisms include: 1) sympathetic nervous systemic activation; 2) formation of reactive oxygen species; 3) production of inflammatory mediators (interleukin 6 and tumor necrosis factor); 4) release of adipocyte derived factors (leptin, adiponectin, resistin); and 5) alteration of the hypothalamic-pituitary-axis (HPA).5,6 At a more comprehensive level, the interaction between OSA and glucose disorders is likely complex. Hyperglycemia and glucose disorders represent a spectrum of disease and a multistep process along a continuum. In the natural development of T2DM, there is initially normal glucose tolerance followed by insulin resistance and an increase in insulin output (compensatory hyperinsulinemia). Eventually, glucose intolerance develops, with failure of pancreatic β cells, and the clinical expression of diabetes. It is possible that in susceptible individuals, the presence of untreated OSA accelerates progression along this continuum of glucose dysregulation.6

Interventional studies are often valuable for explicating causal pathways as well as therapeutic impact. Positive airway pressure (PAP) mitigates the effects of sleep fragmentation and intermittent hypoxia. Consequently, it would be reasonable to assume that treating OSA with PAP therapy would improve glucose homeostasis and glycemic control. However, results from PAP intervention studies have yielded mixed results.7-9 The literature is difficult to synthesize and interpret due to heterogeneity between studies with regards to glycemic outcome measures and duration of PAP therapy. Thus far, the evidence is strongest for a positive PAP effect on glycemic measures in non-diabetic individuals with moderate or severe OSA.7,8 It is possible that chronicity of diabetes is an important factor influencing PAP effect on glucose measures. For example, if an individual has already progressed to a point of complete pancreatic β cell compromise, glycemic dysfunction may not be reversible despite treatment of OSA. Moreover, if a risk factor (i.e., OSA) is more severe, its overall contribution to glucose dysregulation is likely to be more substantial. Thus, treatment of severe OSA, with more hypoxic stress and sleep fragmentation, may have a more pronounced effect on glycemic measures versus mild OSA. Stratification by disease duration, disease severity and PAP adherence may help clarify inconsistencies noted in PAP intervention trials.

Cardiovascular disease remains the leading cause of death worldwide. Early identification and management of modifiable risk factors is a priority in the prevention and risk reduction of cardiac disease. OSA has been established as an independent risk factor for a multitude of cardiovascular diseases. Additionally, the association between OSA and T2DM further compounds the effects of OSA on cardiovascular health. Screening for cardiovascular disease and T2DM is part of routine healthcare. However, despite the fact that OSA is common, affecting 24% of men and 9% of women, it is estimated that 80-90% of people with OSA are undiagnosed.10,11 The public health costs of undiagnosed OSA are difficult to ignore, especially given its association with cardiovascular disease and diabetes. Undoubtedly, there is value in early case identification of OSA. Routine screening with OSA questionnaires or simple inquiry about sleep-related symptoms in cardiac patients and diabetics may be worthwhile. Furthermore, the advent of home sleep testing has made it possible to economically and efficiently diagnose OSA and expeditiously initiate therapy. Thus, there is immense potential to curtail adverse health outcomes in patients with cardiovascular disease, diabetes, or both by simply by staying alert to sleep issues.


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Keywords: Adipocytes, Adiponectin, Arousal, Blood Glucose, Cardiovascular Diseases, Cause of Death, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Glucose, Glucose Intolerance, Heart Diseases, Homeostasis, Hyperglycemia, Insulin, Insulin Resistance, Interleukin-6, Intervention Studies, Leptin, Obesity, Outcome Assessment, Health Care, Polysomnography, Prevalence, Public Health, Reactive Oxygen Species, Resistin, Risk Factors, Risk Reduction Behavior, Self Report, Sleep Apnea Syndromes, Sleep Apnea, Obstructive, Sleep Deprivation, Tumor Necrosis Factors, Metabolic Syndrome

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