Breathing new life into cardiovascular risk: sleep disordered breathing and nocturnal hypoxia as a hidden threat in type 2 diabetes

This editorial refers to ‘Nocturnal hypoxaemic burden is associated with incident major adverse cardiovascular events in patients with type 2 diabetes’, by S. Driendl et al., https://doi.org/10.1093/eurjpc/zwaf259. Type 2 diabetes (T2DM) remains one of the most pressing public health challenges of our time. Its global prevalence continues to rise, accompanied by an increasing burden of cardiovascular diseases (CVDs), which often culminate in major adverse cardiovascular events (MACE), such as myocardial infarction, stroke, and cardiovascular death.1 Despite advances in diabetes management, the complex interplay between metabolic dysregulation and cardiovascular complications beyond glycaemic control remains insufficiently understood.2 New insights, however, are emerging, shedding light on potential biomarkers and factors that could serve as therapeutic targets to mitigate cardiovascular risk in T2DM patients.3,4 Sleep-disordered breathing (SDB) has gained increasing attention in the cardiovascular risk profile of patients with T2DM, and includes conditions such as obstructive sleep apnoea (OSA), central sleep apnoea and obesity hypoventilation syndrome. Sleep-disordered breathing is prevalent in individuals with T2DM, with studies suggesting that up to 50% of these patients may be affected.5 The link between SDB and MACE is well-established, with interrupted sleep patterns and intermittent hypoxia demonstrated to significantly elevate the risk of cardiovascular events.6 The mechanisms behind this include increased sympathetic nervous system activity, endothelial dysfunction, systemic inflammation, and elevated blood pressure,7 all of which can exacerbate atherosclerosis and promote the development of CVDs. Given that T2DM already imposes a heightened cardiovascular risk, the combination of these factors with SDB could create a perfect storm, further increasing the likelihood of MACE in this population. In the paper published this month by Driendl et al.,8 analysing the longitudinal data from the DIACORE cohort study has contributed to this growing body of knowledge by exploring the role of nocturnal hypoxemic burden (NHB) in the development of MACE among individuals with T2DM. The study, conducted in a cohort of 1255 patients, employed overnight oximetry (using a two channel ambulatory monitoring device—ApneaLink®, ResMed) to measure the cumulative time spent with oxygen saturation below 90% (T90), an indicator of sleep hypoxia. The investigators distinguished between two types of desaturation events: acute desaturations (T90desaturation) and non-specific drifts in oxygen saturation (T90non-specific). This differentiation allows for a better phenotyping the patient and more nuanced understanding of how different types of oxygen desaturation contribute to cardiovascular risk. The study revealed that an increased T90, particularly the T90non-specific component, was independently associated with an elevated risk of incident MACE, even after adjusting for known cardiovascular risk factors like age, sex, and diabetes duration. Specifically, the highest quartile of T90 was linked to a 48% higher risk of MACE compared to the lowest quartile. Moreover, the association with T90non-specific was even more pronounced, with an adjusted hazard ratio of 1.62 for the highest quartile compared to the others. This suggests that even subtle, non-acute fluctuations in oxygen saturation during sleep could be contributing to the heightened cardiovascular risk in T2DM patients. The association between apnoea hypopnoea index (AHI) remains less clear. Although the authors in this paper state that the AHI was not significantly associated with an increased risk of MACE, the simple two channel ambulatory monitoring device used in the DIACORE cohort study is not a reliable measure of AHI. However, other cohort studies investigating the prognostic significance of AHI using gold standard polysomnography have reported similar findings, where OSA-related T90 and mean heart rate, but not AHI, were robust predictors of MACE.9 Other population-based epidemiological observational studies have shown a dose–response relationship between OSA severity and cardiovascular events, particularly in younger and in sleepy patients.10 There are several implications of the research presented by Driendl et al. In particular, the data provide evidence for the potential utility of oximetry as a simple, non-invasive tool to identify individuals at higher risk of cardiovascular events within the T2DM population. While the link between SDB and CVD is well-established, this study highlights that even in the absence of overt apnoeas or hypopneas—conditions typically monitored through polysomnography—nocturnal hypoxaemia can still pose a significant cardiovascular risk. However, the study’s findings also raise important questions that warrant further investigation. The differentiation between acute desaturations and non-specific oxygen drift is intriguing but requires more clarification in future studies. What mechanisms drive the non-specific drift in oxygen saturation, and why does it appear to have such a strong association with cardiovascular outcomes? Could these subtle fluctuations be indicative of underlying autonomic dysregulation, inflammation, or other pathological processes that exacerbate vascular damage in T2DM patients? These are critical questions that remain unanswered and will require rigorous research to unpack. Additionally, while the study shows a significant association between NHB and MACE, it is important to remember that correlation does not imply causation. Further longitudinal studies, including interventional trials, are needed to determine whether reducing nocturnal hypoxia—either through lifestyle modifications, pharmacotherapy, or continuous positive airway pressure (CPAP) therapy—can lead to a tangible reduction in cardiovascular events among people with T2DM. In conclusion, the study from the DIACORE cohort adds a new layer of complexity to our understanding of cardiovascular risk in T2DM. It suggests that measuring and addressing NHB, particularly through simple oximetry, could be an important step forward in mitigating the cardiovascular risks that accompany diabetes. However, as the field progresses, we must remain cautious with a need for additional studies to confirm these findings and explore underlying mechanisms. If validated, these insights could not only enhance our ability to predict cardiovascular events in patients with T2DM but also improve our strategies for prevention and treatment. No new data were generated or analysed in support of this article.