Type 2 Diabetes is an important chronic illness associated with high morbidity, mortality and economic burden. The prevalence of Type 2 Diabetes has.been increasing with the Obesity Epidemic. It has been shown in numerous studies that individuals with obstructive sleep apnea (OSA) have an increased prevalence of insulin resistance and type 2 diabetes mellitus. Although these two diseases share risk factors such as obesity, several large cross-sectional studies have shown an independent association between OSA severity and insulin resistance and type 2 diabetes. Furthermore, several longitudinal studies have shown that OSA is a risk factor for incident diabetes, even after adjusting for potential confounders. A study of more than 8500 Canadian patients followed for up to 67 months at the University of Toronto demonstrated that the severity of sleep apnea predicted the risk for incident diabetes. These individuals did not have diabetes at baseline. Overall, 11.7% of the patients developed diabetes, but in patients who had sleep apnea with an Apnea Hypopnea Index (AHI) above 30, there was a 30% higher risk of developing diabetes that in those patient who had a normal AHI (below 5). In addition, patients with mild or moderate OSA had an 23% increased risk of developing diabetes. The risk factors for diabetes in this study included the AHI during rapid eye movement (REM) sleep as well as measures of oxygen desaturation, sleep deprivation and activation of sympathetic nervous system (as indicated by a higher mean heart rate while asleep). This would also tend to support the hypothesis that the development of diabetes is related to the increased sympathetic drive seen with upper airway obstruction. An another possible mechanism for this association would be the increased oxidative stress caused by intermittent hypoxia. In patients with metabolic syndrome, sleep apnea has been independently associated with increased glucose and triglyceride levels as well as markers of inflammation, arterial stiffness and atherosclerosis. Therefore, sleep apnea may also exacerbate the cardiometabolic risk of obesity and metabolic syndrome.
There is mounting evidence that treatment of OSA with CPAP can improve insulin sensitivity, in some studies as soon as 48 hours after CPAP therapy was initiated. In addition, improved insulin sensitivity persisted after 3 months of follow up even without a change in body weight. Both epidemiological and laboratory studies have shown that short sleep times and/or sleep fragmentation in the absence of OSA can also adversely impact glucose metabolism. Plasma ghrelin and leptin levels have been shown to be elevated is OSA patients and these levels return toward normal after CPAP therapy. This would indicates that these elevated levels are not caused by obesity alone. These compounds influence appetite and energy homeostasis and could be important in the relationship between OSA and Type 2 Diabetes
It is important to keep in mind when reviewing studies that many patients with OSA are currently undiagnosed. In addition, the sensitivity for diagnosis may vary depending upon what test is used to diagnose OSA (overnight oximetry testing, home sleep study versus monitored polysomnography). OSA has been shown to be an important risk factor for cardiovascular disease and mortality which is especially concerning in a diabetic population.
Based on current evidence, clinicians should systematically evaluate the risk of OSA in their patients with Type 2 Diabetes, and conversely should assess glucose tolerance carefully in patients with known OSA. Hopefully, additional clinical and basic research will help to clarify the complex interactions between obesity, Type 2 Diabetes and OSA.
By Daniel T. Layish M.D., F.A.C.P., F.C.C.P., F.A.A.S.M.