PDF(Pubmed)
Abstract：
Patients with obstructive sleep apnea (OSA) experience insulin resistance and its clinical consequences, including hypertriglyceridemia, reduced high density lipoprotein-associated cholesterol (HDL-c), visceral adiposity, hepatic steatosis, increased epicardial fat thickness, essential hypertension, glucose intolerance, increased risk for type 2 diabetes, chronic kidney disease, subclinical vascular damage, and increased risk for cardiovascular events. Obesity is a major contributor to OSA. The prevalence of OSA is almost universal among patients with severe obesity undergoing bariatric surgery. However, insulin resistance and its clinical complications occur in OSA patients irrespective of general obesity (body mass index). In OSA patients, apnea episodes during sleep induce oxyhemoglobin desaturation and tissue hypoxia. Insulin resistance is an adaptive response to tissue hypoxia and develops in conditions with limited tissue oxygen supply, including healthy subjects exposed to hypobaric hypoxia (high altitude) and OSA patients. Indicators of oxyhemoglobin desaturation have been robustly and independently linked to insulin resistance and its clinical manifestations in patients with OSA. Insulin resistance mediates the elevated rate of type 2 diabetes, chronic kidney disease, and cardiovascular disease unexplained with traditional cardiovascular risk factors present in OSA patients. Pathophysiological processes underlying hypoxia-induced insulin resistance involve hypoxia inducible factor-1 upregulation and peroxisome proliferator-activated receptor-gamma (PPAR- γ ) downregulation. In human adipose tissue, PPAR- γ activity promotes glucose transport into adipocytes, lipid droplet biogenesis, and whole-body insulin sensitivity. Silencing of PPAR- γ in the adipose tissue reduces glucose uptake and fat accumulation into adipocytes and promotes insulin resistance. In conclusion, tissue hypoxia drives insulin resistance and its clinical consequences in patients with OSA, regardless of body mass index.
摘要：
阻塞性睡眠呼吸暂停（OSA）患者经历胰岛素抵抗及其临床后果，包括高甘油三酯血症,降低高密度脂蛋白相关胆固醇（HDL-c），内脏肥胖,肝脂肪变性,心外膜脂肪厚度增加，原发性高血压,葡萄糖不耐受,2型糖尿病的风险增加，慢性肾病,亚临床血管损伤，增加心血管事件的风险。肥胖是OSA的主要原因。OSA的患病率在接受减肥手术的严重肥胖患者中几乎是普遍的。然而,OSA患者的胰岛素抵抗及其临床并发症的发生与一般肥胖（体重指数）无关。OSA患者中,睡眠中的呼吸暂停发作引起氧合血红蛋白去饱和和组织缺氧。胰岛素抵抗是对组织缺氧的适应性反应，在组织氧供应有限的条件下发展。包括暴露于低压低氧（高海拔）的健康受试者和OSA患者。氧合血红蛋白去饱和指标与OSA患者的胰岛素抵抗及其临床表现密切相关。胰岛素抵抗介导2型糖尿病发病率升高,慢性肾病,OSA患者中存在传统心血管危险因素无法解释的心血管疾病。缺氧诱导胰岛素抵抗的病理生理过程涉及缺氧诱导因子-1上调和过氧化物酶体增殖物激活受体-γ(PPAR-γ)下调。在人体脂肪组织中，PPAR-γ活性促进葡萄糖转运至脂肪细胞，脂滴生物发生，和全身胰岛素敏感性。脂肪组织中PPAR-γ的沉默减少葡萄糖摄取和脂肪向脂肪细胞的积累并促进胰岛素抵抗。总之,组织缺氧导致OSA患者的胰岛素抵抗及其临床后果，不管体重指数。
