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There is significant pathogenic and epidemiological overlap between diabetes and obstructive sleep apnea (OSA). There may be a possible association between OSA and diabetes and their impact on cardiovascular diseases (CVDs). Identifying and managing OSA in individuals with diabetes at an early phase could potentially reduce the risk of CVDs and its related complications.
OSA is a prevalent sleep disorder characterized by repeated upper airway obstruction during sleep. This results in reduced oxygen intake by the lungs, increased carbon dioxide levels in the body, and frequent sleep pattern disruptions. It has been hypothesized to elevate the risk of various CVDs, including stroke, in affected individuals [20]. Although the specific biological processes that underlie the association between CVD and OSA are not entirely understood, some mechanisms have been postulated, such as changes in chest pressure, heightened activity in the sympathetic nervous system, inflammation, and oxidative stress in blood vessels due to cycles of oxygen deprivation and restoration during sleep [20]. The sympathetic nervous system is hypothesized to be activated due to heightened sympathetic drive induced by repeated episodes of apnea and hypopnea, resulting in lower amounts of oxygen in the blood and increased carbon dioxide levels. Recurrent upper airway collapse during sleep, which results in the partial or total cessation of airflow despite continued respiratory effort, is a defining feature of OSA. This can increase respiratory effort against the blocked upper airway, leading to negative intrathoracic pressure. Research has suggested that OSA may be linked to higher levels of inflammatory cytokines and metabolic dysregulation, which may contribute to the development of atherosclerosis. However, due to the complex and diverse nature of OSA, the precise mechanisms that link it to CVD remain somewhat unclear [21].
The presence of diabetes with OSA enhances CVD risk. This is possible because OSA is associated with repetitive episodes of hypoxia–reoxygenation, triggering a cascade of metabolic and inflammatory changes that exacerbate pre-existing metabolic and cardiovascular risk factors in diabetes [11]. One potential mechanism involves insulin resistance, which is common in diabetes and known to promote inflammation and oxidative stress [22]. OSA is linked with impaired glucose metabolism and increased insulin resistance, leading to further inflammation, endothelial dysfunction, and the development of atherosclerosis and CVDs [23]. Another potential mechanism involves activating the renin–angiotensin–aldosterone system (RAAS), associated with maintaining blood pressure (BP). OSA activates the RAAS system, leading to an increase in BP and causing volume overload, contributing to the development of hypertension and CVDs [24]. Additionally, OSA is associated with increased sympathetic nervous system activity, which can further exacerbate hypertension and CVD risk in diabetes. Sympathetic activation can increase heart rate and vasoconstriction, leading to arrhythmias [25]. Overall, the mechanisms linking CVD and OSA in diabetics are likely multifactorial and involve a complex interplay between metabolic and inflammatory pathways.
Few studies explored the relationship with individual CVDs. For example, a cohort study conducted by Adderly et al. revealed that people with DM who developed OSA were at a greater risk of developing CVDs by over 50% [26]. Individuals with diabetes who developed OSA face a greater risk of peripheral neuropathy (PN), AF, diabetic foot disease (DFD), CKD, and all-cause mortality when compared with diabetics without OSA, even after adjusting for potential confounding factors [26]. This study also found that the newly diagnosed DM and OSA patients were at high risk of composite PN, DFD, CVD, and albuminuria [26]. However, the secondary analysis found no significant association between the individual factors of composite CKD, AF, CVD outcome, and all-cause death. The difference may be due to the shorter diabetes duration or better prevention in the OSA group before diabetes diagnosis. Similarly, another observational study found that individuals undergoing coronary artery bypass grafting (CABG) had a relatively higher prevalence of developing OSA and DM [27].The study also found that individuals with both OSA and DM had an elevated probability of emerging MACCEs and were more likely to be hospitalized for HF [27]. Findings further demonstrated that the presence of OSA and DM is independently related to the risk of MACCEs and hospitalization for HF following CABG, even after controlling for left ventricular ejection fraction and medication use [27]. However, it should be mentioned that the study had a few limitations, such as the possibility of unknown or unmeasured confounding variables, and the generalizability of the findings to emergency CABG or major non-cardiac-related surgeries may be limited. Also, the predominantly Asian study population had a limited representation of women subjects [27].