The global prevalence of T2DM among adults aged >18 years has increased from 4.7% in 1980 to 8.5% in 2014 (1). Epidemiological surveys have revealed that the prevalence of T2DM has exceeded 10% in China and the United States (2, 3), and the incidence of NAFLD has exceeded 15% (4).
In addition, with the increasing epidemic of obesity and metabolic diseases, the prevalence of obstructive sleep apnea syndrome (OSAS) among adults has also been increasing. OSAS is caused by narrowing, obstruction, and nerve regulatory factor obstacles within the upper respiratory tract. This complex syndrome manifests with sleep apnea and hypopnea and is accompanied by hypoxia, snoring, daytime sleepiness, and other symptoms (5, 6).
Moreover, patients with OSAS have a greater risk of T2DM and related metabolic disorders.
OSAS and Obesity
The accumulation of visceral fat in obese patients is a key risk factor for OSAS. The analytical results obtained from examining the intra-abdominal fat areas of obese patients with or without OSAS showed that obese patients with OSAS have a significantly larger visceral fat area and an increased ratio of visceral to total fat compared with obese patients without OSAS (9). In addition, the apnea–hypopnea index (AHI), an index used to indicate the severity of sleep apnea and represented by the number of apnea and hypopnea events per hour of sleep, has been positively correlated with the size of the visceral fat area, indicating that the incidence of OSAS increases in patients with large visceral fat areas (10, 11). Therefore, visceral adipose tissue is a key risk factor for OSAS.
In addition, a myriad of studies have demonstrated that the adipose tissue is not only the place in which the body stores energy and triglycerides but is also an important endocrine organ. A number of cytokines and inflammatory factors secreted by the adipose tissue regulate the homeostasis of glucose and lipid metabolism and play key roles in the morbidity of OSAS.
First, leptin, a peptide hormone encoded by the ob gene, regulates appetite, obesity, and insulin sensitivity by binding to its receptor (leptin receptor) (12). Many reports have demonstrated that serum leptin levels are positively correlated with the AHI, hypoxemia, and body mass index in patients with OSAS (13, 14). Thus, the higher the serum leptin level, the greater the AHI and the longer the duration of hypoxemia (13–16). In addition, De Santis et al. (17) reported that the plasma levels of leptin are markedly reduced in patients with OSAS treated with continuous positive airway pressure. Thus, it was predicted that the high concentration of leptin in serum could be involved in the pathogenesis of OSAS.
Although the reasons for the higher leptin levels in OSAS remain poorly understood,we have speculated that leptin resistance, a very common condition in obese patients (18), can directly induce hyperleptinemia.
(…)
Studies have demonstrated that inflammatory cytokines are significantly increased in the plasma of patients with OSAS (39), and their levels become remarkably reduced after continuous positive airway pressure therapy (40). Therefore, inflammatory cytokines are associated with the pathophysiological processes of OSAS. In summary, abnormally secreted adipokines and inflammatory cytokines play important roles in the pathogenesis of OSAS. Further studies into their mechanisms could provide promising strategies for treating OSAS.
OSAS and T2DM
The incidence of hyperglycemia, insulin resistance, and T2DM in patients with OSAS is much greater than the incidence in healthy people. The decline in sleep oxygen saturation levels has also been correlated with the fasting blood glucose level and the blood glucose concentration in the 2-hour oral glucose tolerance test, indicating that the severity of OSAS correlates positively with insulin resistance (41). More importantly, the relationship between OSAS and insulin resistance also applies to nonobese patients. The data from multiple populations have shown that AHI is an independent risk factor for insulin resistance and T2DM.
Some studies have reported that the intermittent hypoxemia and oxidative stress in patients with OSAS could be key factors leading to insulin resistance (43). These results have shown that hypoxemia can affect ATP synthesis in pancreatic islet b-cells and thereby inhibit insulin secretion. Second, hypoxemia decreases the phosphorylation of insulin receptor tyrosine kinases and reduces the effects and sensitivity of the insulin receptors. Third, hypoxemia promotes the excitability of sympathetic nerves, which can elevate the blood glucose level and impair glucose tolerance by improving liver glycogenolysis and gluconeogenesis processes. Fourth, hypoxemia and hypercapnia can stimulate chemoreceptors, leading to increased levels of epinephrine and glucocorticoid to antagonize the biological effects of the insulin. Finally, hypoxemia and oxidative stress cause the expression and release of inflammatory cytokines, resulting in insulin resistance.
OSAS and NAFLD
(…)
Conclusion
OSAS is closely related to the presence of obesity, insulin resistance, T2DM, NAFLD, and related metabolic diseases (60). However, the underlying mechanisms of these diseases require further exploration using animal models and clinical data. However, because of the lifestyle changes in modern society, such as the high nutritional intake and reduced physical activity, the incidence of these diseases has been increasing rapidly. Therefore, it is urgent and necessary to screen patients with OSAS for metabolic diseases and to reduce the incidence of metabolic diseases in patients with OSAS by the implementation of appropriate treatment strategies.
Referência :
(1) Diabetes. 2005 Jun;54(6):1615-25.