Association of Sleep Apnea Severity and Obesity with Insulin Resistance, C-Reactive Protein, and Leptin Levels in Male Patients with Obstructive Sleep Apnea

Abstract

Obesity is the major confounding factor in the relationship between obstructive sleep apnea and increased risk for cardiovascular disease. The aim of the study was to investigate the association of sleep apnea severity with insulin resistance, leptin, and CRP levels in a cohort of male patients. Sixty-seven men referred to our sleep laboratory for evaluation of suspected obstructive sleep apnea syndrome (OSAS) were divided into three groups according to apnea severity: non-OSAS group (n=15), mild to moderate OSAS group (n=26), and severe OSAS (n=26). Insulin resistance was estimated by the homeostasis model assessment method. HOMA values were similar in the three groups: (3.2+/-2.2 vs. 3.3+/-1.8 vs. 3.6+/-1.5, respectively, p=0.71). Leptin levels were higher in the mild to moderate OSAS group (23.1+/-21.8 ng/ml, p<0.05) and in the severe OSAS group (20.2+/-17.5 ng/ml, p<0.05) than in the non-OSAS group (9.4+/-6.4 ng/ml). CRP levels were significantly higher in severe sleep apnea (0.35+/-0.3 vs. 0.19+/-0.1 mg/dl, p<0.05). In multiple regression analyses, waist-to-hip ratio (WHR) was the most significant determinant of HOMA estimation for insulin resistance. WHR and the percentage of total sleep time spent with hypoxemia (%TST with SaO2 <90%) were significant predictors for leptin levels, while body mass index (BMI) and the %TST with SaO2 <90% were the best predicting parameters for CRP levels. Insulin resistance estimated by the HOMA method in male patients with OSAS was not associated with sleep apnea severity independent of obesity. The severity of nocturnal hypoxemia was associated with leptin and CRP levels independent of obesity.

Sleep, sleep-disordered breathing and metabolic consequences

“…Similar data have been obtained in samples of OSA patients (tables 3 and 4) [64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80], with a large prevalence of positive [63,[64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79] rather than negative [78][79][80] studies. In clinical populations, OSA patients characterised by full-PSG were significantly more likely to have impaired glucose tolerance (IGT) and diabetes than subjects free of OSA syndrome (OSAS) [71].…”

“…In a population-based cohort, IGF-1 significantly increased after CPAP treatment [117]. However, in OSA patients' improvement in IGF-1 after CPAP was reported to occur only in patients presenting with EDS [76]. Adiponectin is known to counteract the effects of IR [120], and the effects of OSA treatment on adiponectin have been assessed with controversial results.…”

Serum Inflammatory Markers in Obstructive Sleep Apnea: A Meta-Analysis

“…There was heterogeneity in this endpoint (df (Q) 31, p < 0.0001, I 2 = 96.4) (Figure 1). [56][57][58][59][60][61][62][63][64][65][66][67][68] The second analysis was performed with studies reporting OSA patients in groups (mild, moderate, or severe): standardized mean difference ranged from -0.18 to 8.59. The pooled mean difference was calculated to be 1.07 (LL 0.60 to UL 1.54, p < 0.0001).…”

Obstructive sleep apnea syndrome and cardiovascular disease: The influence of C-reactive protein

“…Recent studies, however, have shown a close correlation of CRP level with OSAS severity meaning that the higher the AHI, the higher the levels and CRP elevation seems to be independent from visceral obesity in patients with OSAS [4,19,21,24,34,38,[48][49][50][51][52][53][54] . The above studies imply that factors other than adiposity may have a central role for the proinflammatory status observed in OSAS.…”