Supplementary Material for: Insulin Resistance, but Not Obstructive Sleep Apnea Is Associated with Hepatic Steatosis in Chinese Patients with Severe Obesity

Introduction Severe obesity often present with nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA). Emerging researches suggest OSA plays an important role in NAFLD development and progression while the relationship between OSA and NAFLD is still conflicting . The interaction of OSA and NAFLD should be further evaluated as obesity surges. The purpose of this study was to assess the prevalence of OSA and NAFLD in patients with obesity undergoing bariatric surgery, and evaluate the association between OSA and severity of NAFLD. Methods 141 patients with severe obesity undergoing preoperative polysomnography and intraoperative liver biopsy during bariatric surgery was investigated. Clinical, anthropometric variables, liver enzymes, fasting blood glucose, fasting serum insulin, and homeostasis model assessment (HOMA-IR) were measured. The severity of NAFLD was assessed by degree of steatosis, ballooning, intralobular inflammation and NAFLD activity score (NAS). The diagnosis and severity assessment of OSA was based on an apnea/hypopnea index (AHI). Results OSA was diagnosed in 127 (90.07%), NAFLD in 124 (87.94%), and non-alcoholic steatohepatitis (NASH) in 72 (51.06%) patients. There was a statistically difference in body mass index (BMI), waist circumstance, neck circumstance, high-density lipoprotein-cholesterol (HDL), fasting insulin, and HOMA-IR among the three groups divided by the severity of AHI. In addition, the distribution of hepatic steatosis grades among the three groups was statistically different (P=0.025). AHI was significantly associated with HOMA-IR and hepatic steatosis when assessing the association between OSA parameters and liver histology in NAFLD(P< 0.05). Patients with steatosis of grade 1-3 had significantly elevated aspartate aminotransferase(AST), alanine aminotransferase(ALT), gamma glutamyl transferase (GGT),triglycerides (TG), fasting insulin, fasting glucose, HOMA-IR, and AHI compared with the patients with steatosis of grade 0. In a multivariable logistic analysis, the positive association between AHI and hepatic steatosis attenuated after adjusting for HOMA-IR. Conclusion Prevalence of OSA and NAFLD was high in patients with obesity eligible for bariatric procedures. HOMA-IR, but not AHI, was an independent risk factor for hepatic steatosis in this population.

引言 重度肥胖患者常合并非酒精性脂肪性肝病（nonalcoholic fatty liver disease, NAFLD）与阻塞性睡眠呼吸暂停（obstructive sleep apnea, OSA）。现有新兴研究提示，OSA在NAFLD的发生与进展中发挥重要作用，但二者间的关联仍存在争议。随着肥胖患病率持续攀升，OSA与NAFLD的相互作用亟待进一步明确。本研究旨在评估拟行减重代谢手术的重度肥胖患者中OSA与NAFLD的患病率，并探讨OSA与NAFLD严重程度的关联。
方法 本研究纳入141例拟行减重代谢手术的重度肥胖患者，所有患者均接受术前多导睡眠监测（polysomnography）及术中肝脏活检（liver biopsy）。收集患者的临床资料、人体测量学指标、肝酶水平、空腹血糖、空腹血清胰岛素及稳态模型胰岛素抵抗指数（homeostasis model assessment, HOMA-IR）。NAFLD的严重程度通过脂肪变程度、气球样变、小叶内炎症及非酒精性脂肪性肝病活动度评分（NAFLD activity score, NAS）进行评估；OSA的诊断及严重程度分级则基于呼吸暂停低通气指数（apnea/hypopnea index, AHI）。
结果 本研究共纳入127例（90.07%）OSA确诊患者、124例（87.94%）NAFLD确诊患者，其中72例（51.06%）确诊为非酒精性脂肪性肝炎（non-alcoholic steatohepatitis, NASH）。按AHI严重程度分为三组后，三组患者的体质量指数（body mass index, BMI）、腰围、颈围、高密度脂蛋白胆固醇（high-density lipoprotein-cholesterol, HDL）、空腹胰岛素水平及HOMA-IR均存在统计学差异。此外，三组间肝脏脂肪变分级的分布亦存在显著统计学差异（P=0.025）。在分析NAFLD患者的OSA参数与肝脏组织学特征的关联时，AHI与HOMA-IR及肝脏脂肪变程度显著相关（P<0.05）。与脂肪变分级为0的患者相比，脂肪变分级1~3级的患者其天门冬氨酸氨基转移酶（aspartate aminotransferase, AST）、丙氨酸氨基转移酶（alanine aminotransferase, ALT）、γ-谷氨酰转移酶（gamma glutamyl transferase, GGT）、甘油三酯（triglycerides, TG）、空腹胰岛素、空腹血糖、HOMA-IR及AHI水平均显著升高。多变量logistic回归分析显示，在校正HOMA-IR后，AHI与肝脏脂肪变间的正相关关系有所减弱。
结论 拟接受减重代谢手术的肥胖患者中，OSA与NAFLD的患病率均较高。在该人群中，HOMA-IR而非AHI是肝脏脂肪变的独立危险因素。