Obstructive sleep apnea: Overlooked comorbidity in patients with diabetes

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.