Obstructive sleep apnea: Overlooked comorbidity in patients with diabetes

Table 1 The impact of obstructive sleep apnea on macrovascular complications in type 2 diabetes mellitus

Ref.	Summary of findings
Aurora and Punjabi[4]	Evidence of a bidirectional relationship between OSA and T2DM; OSA exacerbates glycemic control, and T2DM increases OSA severity
Alshehri et al[25]	Presence of DM with abnormal ABI linked to severe OSA; OSA may worsen PAD through hypoxia-induced sympathetic activity
Zhao et al[26]	OSA identified as an independent risk factor for LEAD in T2DM patients, with risk levels increasing alongside OSA severity
Protasiewicz Timofticiuc et al[27]	OSA severity in T2DM patients associated with increased 10-year risk of coronary heart disease; highlights need for prospective studies and precise diagnostic methods
Hermans et al[28]	OSA associated with adverse atherogenic indices and inflammatory markers, indicating a higher risk of CAD
Adderley et al[29]	Incident OSA in T2DM patients linked to increased macrovascular complications and mortality, but not PAD
Strausz et al[30]	Comparable risks of CHD in T2DM patients with and without OSA; higher risk in females
Labarca et al[31]	Coexistence of OSA and DM in the SantOSA cohort showed increased risks of stroke and cardiovascular mortality
Su et al[32]	In older adults, coexistence of OSA and DM increased the risk of MACE and hospitalization for unstable angina, especially in females over 70 years
Wang et al[33]	Concurrent OSA and T2DM in ACS patients increased the risk of MACCE, particularly with elevated baseline glucose or HbA1c levels
Wang et al[34]	OSA in DM patients post-PCI linked to increased risk of MACEs and all-cause mortality

OSA: Obstructive sleep apnea; T2DM: Type 2 diabetes mellitus; ABI: Ankle-brachial index; PAD: Peripheral arterial disease; LEAD: Lower extremity artery disease; CAD: Coronary artery disease; CHD: Coronary heart disease; MACE: Major adverse cardiovascular events; ACS: Acute coronary syndrome; MACCE: Major adverse cardiovascular and cerebrovascular events; PCI: Percutaneous coronary intervention.

Table 2 The impact of obstructive sleep apnea on microvascular complications in type 2 diabetes mellitus

Ref.	Summary of findings
Antza et al[35]	Three months treatment with CPAP significantly increased the eGFR and decreased the serum creatinine levels in patients with OSA. Patients with T2D and OSA who were compliant with CPAP had reduced development of proliferative retinopathy over 5 years and lower decline in eGFR over 2.5 years compared to those non-compliant with CPAP or with mild OSA
Tahrani et al[38]	Neuropathy prevalence was higher in patients with OSA than those without (60% vs 27%, P < 0.001)
Zhang et al[40]	Parameters of nocturnal hypoxemia are associated with DN and renal function of T2DM patients. The associated parameters increased from two (the average SPO2 and CT90%) to three (ODI, the lowest SPO2, and CT85%) when the severity of DN increased from microalbuminuria to renal insufficiency. The eGFR was independently correlated with ODI (β = -0.172, P = 0.029) and the lowest SPO2 (β = 0.354, P = 0.004) after adjustments
Leong et al[41]	Studies that performed multi-variable analysis demonstrated significant associations between OSA (assessed using either AHI or ODI) and DKD in T2DM. This was confirmed by meta-analysis (pooled OR 1.73, 95%CI: 1.13-2.64). There was some evidence to suggest that %TST < 90 may have an association with DKD
Tahrani et al[42]	OSA and DN prevalence was 64.3 and 40.2, respectively. DN prevalence was higher in patients with OSA (OSA+) compared with those without OSA (OSA-) (49.3% vs 23.8%, P < 0.001). After adjustment, OSA [OR: 2.64 (95%CI: 1.13-6.16), P = 0.02] remained independently associated with DN. After an average follow-up of 2.5 (0.7) years, eGFR decline was greater in OSA+ compared with OSA- patients [median -6.8% (interquartile range -16.1 to 2.2) vs -1.6% (-7.7 to 5.3%), P = 0.002]
Furukawa et al[43]	Microalbuminuria (model 1: OR, 3.41; 95%CI: 1.85-6.40; model 2: OR, 3.69; 95%CI: 1.85-7.59 and model 3: OR, 3.12; 95%CI: 1.45-6.95) and nephropathy (model 1: OR, 4.51; 95%CI: 1.58-15.1; model 2: OR, 7.31; 95%CI: 2.11-31.6 and model 3: OR, 5.23; 95%CI: 1.45-23.8) were derived as factors from all three statistical models and constantly associated with nocturnal intermittent hypoxia only in women
Shiba et al[44]	4% ODI and CT90% in the PDR group were significantly higher than in the NPDR (4% ODI, 7.8 vs 4.9; P = 0.007; CT90%, 2.2 vs 0.8; P = 0.0006). Lowest SPO2 was significantly lower in the PDR group than in the nonproliferative diabetic retinopathy groups (82.4 vs 87.0; P = 0.0006). Logistic regression analysis identified being younger, having a lower value for the lowest SPO2, and a high HbA1c value to be risk factors for PDR (age: odds ratio, 0.90; 95%CI: -0.86 to −0.94; P < .0001; lowest SPO2: OR, 0.93; 95%CI: 0.88 to 0.99; P = 0.02; hemoglobin A1c: odds ratio, 1.00 to 1.69; P = 0.047)
Abbas et al[45]	OSA was found to be independently associated with both advanced DR [preproliferative (R2) or proliferative (R3)] (OR = 6.29; 95%CI: 1.08-6.65; P = 0.04) and maculopathy (OR = 12.92; 95%CI: 3.97-4.79; P < 0.001). Moreover, OSA severity was directly related to DR grade (r = 0.5, P < 0.001)
Chew et al[46]	Higher AHI (OR 1.04; 95%CI: 1.00, 1.07) and short sleep duration (OR 3.22; 95%CI: 1.18-8.79) were associated with moderate DR. VTDR was associated with moderate OSA (OR 4.73; 95%CI: 1.46-15.31), higher AHI (OR 1.06; 95%CI: 1.02-1.10) and lower minimum SaO2 (OR 0.89; 95%CI: 0.83-0.96). High risk for insomnia was associated with DME (OR 4.01; 95%CI: 1.09-14.73)
Chang et al[47]	An association was seen between DR and severe OSA (OR: 2.18, 95%CI: 1.14-4.18, P = 0.019). Proliferative DR was associated with severe OSA versus no DR (OR: 2.40, 95%CI: 1.12-5.14, P = 0.024) and mild nonproliferative DR (OR: 2.87, 95%CI: 1.26-6.55, P = 0.012). Comparing all nonproliferative DR with proliferative DR, proliferative DR and severe OSA were associated (OR: 2.20, 95%CI: 1.03-4.70, P = 0.043), as well as diabetic macular edema and severe OSA (OR: 2.89, 95%CI: 1.58-5.27, P = 0.001)
Altaf et al[48]	STDR and OSA prevalence rates were 36.1% and 63.9%, respectively. STDR prevalence was higher in patients with OSA than in those without OSA (42.9% vs 24.1%; P = 0.004). After adjustment for confounders, OSA remained independently associated with STDR (OR, 2.3; 95%CI: 1.1-4.9; P = 0.04). After a median follow-up of 43.0 months, patients with OSA were more likely than patients without OSA to develop preproliferative/proliferative DR (18.4% vs 6.1%; P = 0.02). After adjustment for confounders, OSA remained an independent predictor of progression to preproliferative/PDR (OR, 5.2; 95%CI: 1.2-23.0; P = 0.03). Patients who received CPAP treatment were significantly less likely to develop preproliferative/PDR
Kaba et al[49]	OSA prevalence was significantly higher in the DME+ group (70.7%) than DME- group (42.4%, P < 0.05). A significantly lower average minimum SaO2 was noted in OSA+DME+ (81.74%) than OSA+DME- eyes (88.23%, P < 0.05)

OSA: Obstructive sleep apnea; T2D: Type 2 diabetes; eGFR: Estimated glomerular filtration rate; CPAP: Continuous positive airway pressure; DN: Diabetic neuropathy; DKD: Diabetic kidney disease; DR: Diabetic retinopathy; PDR: Proliferative diabetic retinopathy; DME: Diabetic macular edema; STDR: Sight-threatening diabetic retinopathy; ODI: Oxygen desaturation index; AHI: Apnea-hypopnea index; VTDR: Vision-threatening diabetic retinopathy.

Table 3 The impact of obstructive sleep apnea management on type 2 diabetes mellitus control

Ref./study	Summary of findings
The Sleep AHEAD study[50]	Regular exercise on its own helps improve OSA, and the more someone exercises, the lower the chances of having moderate to severe OSA-odds decrease with 1-2 hours per week (0.62), 3-6 hours per week (0.39), and at least 7 hours per week (0.31) compared to those who do not exercise vigorously
Shechter et al[51]	For individuals with T2DM and OSA, weight loss from a lifestyle intervention is more crucial for improving glycemic control than reductions in OSA severity
MIMOSA[52]	The MLG group exhibited improved insulin and HOMA–IR profiles compared to the SCG counterpart
The Interdisciplinary Weight Loss and Lifestyle Intervention for OSA (INTERAPNEA)[53]	Mediterranean lifestyle group demonstrated the potential benefits of interdisciplinary weight reduction and lifestyle therapies in improving the severity, symptoms, and cardiometabolic profiles, including T2DM, of individuals with OSA, including improvements in blood pressure and in glucose and lipid metabolism. In the intervention group, there were lower glucose and insulin levels, and lower HOMA-IR
The SCALE sleep apnea[55]	3.0 mg liraglutide reduced AHI, bodyweight, HbA1c, and SBP significantly compared to the placebo group
Herth et al[63]	The beneficial impact of CPAP on HbA1c levels was influenced by the duration of CPAP use per night, while it was not affected by baseline AHI, BMI, or diabetes duration
Zamarrón et al[65]	Participants in the CPAP treatment arm, with good adherence, exhibited a greater reduction in UACR [MD, -10.56% (95%CI: -19.06 to -2.06); P = 0.015], along with improvements in glycemic control and insulin resistance
Ding et al[59]	Surgical weight loss improves T2DM and OSA control. Mini GBP is associated with highest remission rate while BPD is associated with sustained long term remission

OSA: Obstructive sleep apnea; T2DM: Type 2 diabetes mellitus; MLG: Mediterranean lifestyle group; HOMA-IR: Homeostatic model assessment for insulin resistance; AHI: Apnea hypopnea index; RDI: Respiratory disturbance index; CPAP: Continuous positive airway pressure; SBP: Systolic blood pressure; UACR: Urine albumin creatinine ratio; GBP: Gastric bypass; BPD: Biliopancreatic diversion without duodenal switch.