Abstract
Diabetes and obstructive sleep apnoea (OSA) are interconnected chronic conditions. The increasing prevalence of obesity drives the pathogenesis of these interrelated disorders. OSA, characterised by nocturnal hypoxia resulting from recurrent episodes of upper airway obstruction during sleep, is common in individuals with type 2 diabetes mellitus (T2DM). At the same time, T2DM increases the risk of OSA through mechanisms involving obesity, systemic inflammation, and autonomic dysfunction. OSA increases insulin resistance, impairs glucose tolerance, and worsens glycaemic control. Management strategies should involve early screening for OSA in individuals with T2DM and vice versa. Continuous positive airway pressure (CPAP) therapy improves insulin sensitivity and cardiovascular outcomes, though its impact on glycaemic control remains inconsistent. Emerging evidence suggests that newer anti-obesity medications may reduce OSA severity alongside improving metabolic parameters. Future research should focus on identifying the molecular pathways linking OSA and diabetes, evaluating long-term CPAP benefits, and optimising pharmacological approaches to improve outcomes in both conditions.
Keywords
Introduction
Diabetes and obstructive sleep apnoea (OSA) are closely connected chronic conditions, having short and long-term health consequences. The rising global prevalence of obesity drives the pathogenesis of both disorders. Type 2 diabetes mellitus (T2DM) and OSA not only coexist but also exacerbate each other, creating a vicious cycle that has implications for health and quality of life.[1]
OSA, characterised by recurrent episodes of upper airway obstruction during sleep, is a prevalent disorder that disproportionately affects individuals with diabetes. Conversely, diabetes, a metabolic disorder characterised by persistent hyperglycaemia, has been identified as a risk factor for the development of OSA. The coexistence of OSA and T2DM can lead to a range of adverse health outcomes, including cardiovascular disease (CVD), metabolic derangements, and cognitive decline.[2]
This review focuses on the close relationship between T2DM and OSA, exploring the epidemiological link, the pathophysiological mechanisms, clinical implications, and management strategies. A combined approach to managing the two conditions will improve patient outcomes and reduce the long-term health consequences associated with their co-occurrence.
Epidemiology
The rising and combined prevalence of T2DM and OSA is a public health challenge. The global estimate of the prevalence of diabetes in 2021 in adults aged 20-79 years was 10.5%, impacting 536.6 million people. There was no gender predisposition, but the rates increased with age.[3] On the other hand, 936 million adults aged 30-69 years were affected with OSA, with 425 million having moderate to severe disease.[4]
A recent meta-analysis of 35 observational studies demonstrated a higher prevalence of diabetes in OSA [OR: 2.29, 95% confidence interval (CI): 1.93-2.72]. Conversely, OSA was more common in individuals with diabetes (OR: 2.12, 95% CI: 1.73-2.60).[5] In addition to diabetes (OR: 3.62, 95% CI: 2.75-4.75), OSA increased the risk of impaired fasting glucose (IFG) (OR: 2.34, 95% CI: 1.16-4.72), impaired glucose tolerance (IGT) (OR: 1.58, 95% CI: 1.15-2.15) and impaired glucose regulation (IFG + IGT) (OR: 1.65, 95% CI: 1.12-2.42).[6]
The prevalence of OSA in individuals with diabetes was 54.5% (95% CI: 39.90-69.09).[7] A meta-analysis of 20 studies, including 10,754 participants with T2DM (mean age: 58.6 ± 4.1 years), estimated the prevalence of OSA at 56.0%. Meta-regression revealed that OSA prevalence increased with higher mean age, male percentage, and body mass index (BMI).[8] The prevalence of diabetes in individuals with severe OSA ranges from 15% to 30%.[9] Diabetes was present more often in severe (26%) and moderate (12%) OSA compared to mild OSA (5%).[10] The current evidence highlights a well-established bidirectional epidemiological link between T2DM and OSA.
Pathophysiological Link Between OSA and Diabetes
OSA and T2DM share several pathophysiologic connections. OSA is characterised by intermittent hypoxia due to repeated airway obstruction during sleep, leading to increased sympathetic nervous system activity and oxidative stress, which impair insulin secretion and promote insulin resistance. Additionally, sleep fragmentation affects normal sleep architecture, resulting in hormonal changes such as increased cortisol secretion that decreases insulin sensitivity. Systemic inflammation is another critical factor; OSA elevates pro-inflammatory cytokines like TNF-alpha and IL-6, associated with metabolic dysfunction. Furthermore, obesity, often present in individuals with OSA, alters adipokine secretion, disrupting the action of hormones such as leptin and adiponectin.[11]
Diabetes predisposes to OSA through several mechanisms, primarily related to obesity and metabolic changes. Obesity leads to excess fat deposits around the neck, obstructing the airway during sleep and causing apnoea episodes.[12] Additionally, insulin resistance promotes inflammation and oxidative stress, which may exacerbate airway inflammation and increase the likelihood of upper airway collapse during sleep.[13] Furthermore, autonomic dysfunction from diabetes and insulin resistance can impair airway stability during sleep.[9] The pathophysiologic connection between the two conditions is summarised in Figure 1.
OSA and Risk of Developing Diabetes
OSA significantly increases the possibility of developing T2DM, with the risk being more pronounced in individuals with severe OSA. An observational study of 1,233 participants from the Veteran Affairs Connecticut Healthcare System found that increasing severity of OSA was independently associated with an increased risk of diabetes. The hazard ratio per quartile of OSA severity was 1.43 (CI: 1.10-1.86). Regular use of positive airway pressure therapy attenuated this risk.[14] Another cohort of 8,678 individuals followed over a median of 67 months found that the risk of developing T2DM was 30% higher with severe OSA [apnoea-hypopnoea index (AHI) > 30] compared to those with mild forms (AHI <5).[15] A meta-analysis of 16 cohort studies found OSA increased T2DM risk by 40% (RR: 1.40, 95% CI: 1.32-1.48) over a median follow-up of 10.5 years, with each 5-event/h AHI rise linked to an 8% increased risk (RR: 1.08, 95% CI: 1.01-1.14).[16]
OSA contributes to insulin resistance in adipose tissue and skeletal muscles, pathways critical to the pathogenesis of T2DM. A study using hyperinsulinaemic-euglycaemic clamp with isotopically labelled glucose and palmitate tracers and 18F-fluorodeoxyglucose positron emission tomography demonstrated that OSA was associated with marked insulin resistance of adipose tissue triglyceride lipolysis and glucose uptake into skeletal muscles and adipose tissue. There was no difference between the OSA and control groups in insulin action on hepatic insulin resistance, basal insulin secretion, and glucose-stimulated insulin secretion.[17]
Impact of OSA on Glycaemic Control in Diabetes
OSA has been linked to worsened glycaemic control in individuals with diabetes. Several studies indicate that individuals with OSA have higher glycated haemoglobin (HbA1C) than those without OSA.[18-20] In a cross-sectional study of 66 participants with OSA and T2DM, higher HbA1c correlated with sleep time spent with oxygen saturation below 90% and oxygen desaturation index (ODI) but not with AHI, suggesting that nocturnal hypoxemia specifically could be responsible for hyperglycaemia.[21]
OSA during rapid eye movement (REM) sleep may have a more pronounced impact on glycaemic control. A study with 115 participants found that REM AHI was independently associated with increasing HbA1c levels.[22] Additionally, increasing severity of OSA is associated with higher levels of HbA1c. A study with 60 participants with T2DM found that the adjusted mean HbA1c increased by 1.49% in mild OSA, 1.93% in moderate OSA, and 3.69% in severe OSA compared to controls without OSA.[23]
Impact of Diabetes on OSA
Glycaemic control exerts a beneficial effect on sleep breathing parameters independent of weight loss in T2DM. In a study with 35 participants with T2DM, HbA1c reduction ≥0.5% correlated with AHI improvement.[24] A systematic review suggested that glucose-lowering therapy, especially using sodium-glucose cotransporter-2 inhibitors (SGLT2i), lowered AHI in T2DM.[25] Even glycaemic control for five days significantly reduced nocturnal ODI in individuals with diabetes, but no changes were observed in controls.[26] The mechanisms remain unclear but may involve improved sympathetic activity, reduced chronic inflammation, or changes in central dysregulation.[9]
Glycaemic Benefits of Continuous Positive Airway Pressure (CPAP)
The glycaemic benefits of CPAP therapy for OSA are variable. CPAP improved insulin sensitivity during oral glucose tolerance test (OGTT) and reduced 24-hour blood pressure compared to placebo in a randomised controlled trial (RCT).[27] A meta-analysis of nine RCTs with 443 participants demonstrated that CPAP significantly improved the homeostasis model assessment (HOMA) index but did not alter fasting glucose levels.[28]
Most RCTs performed over three to six months did not demonstrate a significant reduction in HbA1c with CPAP.[29-31] Only a six-month RCT involving 50 patients with OSA and T2DM reported a 0.4% reduction in HbA1c.[32] A 12-week RCT did not demonstrate sustained glycaemic benefit of CPAP over sham treatment. However, greater CPAP adherence (≥4 hours/day) was linked to improved glycaemic control, with ≥7 hours of use significantly reducing HbA1c.[33] In a recently published meta-analysis, CPAP modestly improved insulin sensitivity, reducing fasting plasma insulin by 1.33 mU/L and HOMA-IR by 0.287. Benefits were also observed in individuals with prediabetes. CPAP also led to a mean total cholesterol reduction of 0.064 mmol/L but did not alter HbA1c, triglycerides, HDL- and LDL-cholesterol.[34] Another meta-analysis of seven trials with 691 participants reported a significantly lower HbA1c (SMD: -0.32, 95% CI: -0.60 to -0.03) and fasting glucose (SMD -0.39, 95% CI -0.76 to -0.02).[35] The possible differences in findings could be related to adherence to CPAP, baseline HbA1c, and concomitant medical therapy.
OSA and Diabetic Retinopathy
Several studies have investigated the relationship between OSA and diabetic retinopathy (DR), revealing a possible association and potential implications for management. A retrospective study involving 317 participants with both DR and OSA found that severe OSA was associated with an increased risk of DR (OR: 2.18, 95% CI: 1.14-4.18). Proliferative DR was more likely in those with severe OSA compared to those without DR (OR: 2.40, 95% CI: 1.12-5.14) and those with mild non-proliferative DR (OR: 2.87, 95% CI: 1.26-6.55).[36] A strong association between OSA and macular edema has also been demonstrated.[37] Compared to controls, treatment with CPAP over 12 months enhanced AVR (P = .035) and arteriolar diameter (P = .033). The venular diameter was also reduced, though the decrease was not statistically significant.[38]
Screening for OSA in T2DM
The possibility of OSA should be considered during the assessment of people with T2DM and metabolic syndrome. Individuals with suggestive symptoms such as excessive daytime sleepiness, snoring and witnessed apnoea or gasping and choking during sleep should be evaluated for OSA.[39] Other symptoms that should raise the suspicion of OSA include fatigue, irritability, poor memory, depression, mood changes, morning headaches, sexual dysfunction, and nocturia.[40] Obesity and increased neck circumference (males > 17 inches and females > 16 inches) are valuable predictors. Individuals manifesting complications of OSA, such as resistant or refractory hypertension, atrial fibrillation, nocturnal angina or dysrhythmias, congestive heart failure, stroke, and transient ischemic attacks, should also preferably undergo diagnostic testing.[41]
Several screening tools are available, but none of them are superior to a comprehensive history and physical examination and should not be used as a replacement for polysomnography. The commonly used questionnaires are STOP-BANG, Berlin, and Epworth Sleepiness Scale (ESS). Their predictive performance is similar in people with and without T2DM.[42] In-laboratory polysomnography remains the gold standard for diagnosing OSA. However, for individuals with suspected uncomplicated OSA and moderate to severe pretest probability, home sleep apnoea testing (HSAT) with a type 3 device is a viable alternative.[43]
Screening for Diabetes in OSA
People with OSA should be routinely screened for markers of metabolic disturbance and cardiovascular risk. Minimum testing should include blood pressure measurement, fasting plasma glucose, HbA1c, and lipid profile. A cardiac evaluation guided by cardiovascular risk and functional status should be performed.[44]
Treatment Recommendations for OSA in T2DM
Lifestyle modifications, including weight loss, and avoiding alcohol and smoking, should be the first-line approach. Education and awareness about the long-term risks of OSA are essential. CPAP is the most effective option for moderate to severe cases and should be considered when suitable. Though glycaemic benefit of CPAP is equivocal, it may improve cardiovascular outcome in those with pre-existing CVD.[45] In resistant hypertension, guidelines recommend that OSA should be ruled out. Finally, CPAP treatment of OSA may improve outcomes in people with heart failure.[46]
Choice of Glucose-lowering Medications in T2DM with OSA
Glucose-lowering medications that promote weight loss such as glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RA), dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (tirzepatide), and SGLT2i may benefit individuals with OSA who are overweight or obese.[25,47,48] In persons with moderate to severe OSA, tirzepatide reduced AHI, body weight, hypoxic burden, high-sensitivity C-reactive protein, and systolic blood pressure, and sleep-related patient-reported outcomes. The benefits were seen in both CPAP users and those not on CPAP.[48] The reduction in hypoxic burden with tirzepatide may correlate with lower cardiovascular mortality rates, suggesting additional health benefits beyond OSA management.[49] Tirzepatide recently received the United States Food and Drug Administration approval for the treatment of moderate-to-severe OSA in adults with obesity. This approval marks the first pharmaceutical treatment for this specific indication. Table 1 outlines the best practice recommendations for management of OSA in diabetes.
Practice recommendations for management of OSA in diabetes (references in text)
Future Research
Future research on the interplay between OSA and diabetes should prioritise several key areas. Large-scale epidemiological studies are needed to understand the relationship across diverse populations. Further investigations should confirm the effect of OSA on glucose metabolism and how sleep variables influence T2DM control. Understanding the prevalence and spectrum of OSA in type 1 diabetes is another aspect requiring more insight. Further studies should evaluate the long-term benefits of CPAP therapy on cardiovascular and metabolic outcomes. The role of newer anti-obesity medications in the management of OSA is an emerging area of interest. However, long-term data on their impact are still limited. Questions remain regarding their direct effects on upper airway dynamics, inflammation, and long-term cardiovascular outcomes. Future studies should explore sustained efficacy, adherence, and their role in combination with CPAP or as standalone therapy. Finally, more research is essential to elucidate the molecular pathways linking OSA and diabetes.
Conclusion
OSA and T2DM are interconnected conditions that are driven by common pathophysiologic links such as obesity, chronic inflammation, and sympathetic hyperactivity. OSA exacerbates insulin resistance, worsens glycaemic control, and increases cardiovascular risk, while T2DM contributes to airway instability through inflammatory pathways and autonomic dysfunction. CPAP therapy improves insulin sensitivity and cardiovascular outcomes, though its direct glycaemic benefits remain inconsistent. Newer anti-obesity medications show promise in reducing OSA severity and improving metabolic health. Future research should focus on identifying a personalised approach for these often coexisting conditions.
Footnotes
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
Funding
The authors received no financial support for the research, authorship and/or publication of this article.
Institutional Ethical Committee Approval Number
Not applicable.
Credit author statement
Concept and Design: Viny Kantroo and Saptarshi Bhattacharya.
Data collection: Aditi Chopra and Bhawna Attri.
Data analysis and interpretation: Viny Kantroo and Bhawna Attri.
Manuscript drafting: Viny Kantroo and Saptarshi Bhattacharya.
Critical revision: Sanjay Kara and Aditi Chopra.
Data availability
All data included in the manuscript.
Use of artificial intelligence
No.