2型糖尿病伴或不伴OSAHS发生心血管事件和全因死亡的风险研究

Risk of cardiovascular events and all-cause death in type 2 diabetes mellitus with or without obstructive sleep apnea hypopnea syndrome

Key words:  糖尿病  睡眠呼吸暂停低通气综合征  心血管事件  全因死亡

Key words:  diabetes mellitus  obstructive sleep apnea hypopnea syndrome  cardiovascular events  all-cause death

Abstract:

目的 探讨2型糖尿病伴和不伴阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea hypopnea syndrome, OSAHS)发生主要不良心血管事件(major adverse cardiovascular events, MACE)和全因死亡的风险研究。 方法 此项队列研究使用了2012年9月—2014年9月在上海市东方医院内分泌科住院的成人2型糖尿病患者数据。所有患者均完善便携式睡眠呼吸检测仪监测。根据睡眠呼吸暂停低通气指数(apnea-hypopnea index, AHI)分为单纯2型糖尿病(n=55)、2型糖尿病合并轻度(n=94)、中度(n=29)及重度OSAHS(n=15)4组。收集基线人口学数据、生化指标、临床特征、睡眠参数及随访结果。本研究的主要终点事件是确定发生MACE(即非致命性卒中、非致命性心力衰竭、非致命性心肌梗死)的风险，次要结果是全因死亡的结果。使用Logistic回归风险模型及Kaplan-Meier生存分析来评估2型糖尿病合并OSAHS与事件的相关性。 结果 最终共纳入了146名受试者的数据，中位随访8.0年后(四分位数为5~9年)，146例中的72例(49.3%)发生MACE,42例发生死亡(28.8%)。Logistic回归分析显示，在调整年龄、糖尿病病程、冠状动脉疾病（coronary artery disease, CAD）病史、高血压病史、脑卒中病史调整模型后，中度及重度OSAHS患者增加了2型糖尿病患者MACE事件的发生(OR=0.07，95%CI: 0.01~0.66，P=0.019；OR=0.08,95%CI: 0.01~0.86,P=0.037)。Kaplan-Meier生存分析显示，4组间全因死亡率无明显统计学差异(log-rank test P=0.124)，但2型糖尿病合并重度OSAHS非致命性卒中的发生率明显高于单纯2型糖尿病(log-rank test P=0.016)。 结论 中、重度OSAHS会增加2型糖尿病患者MACE风险，而重度OSAHS会增加2型糖尿病非致命性卒中发生的风险。患有2型糖尿病的OSAHS患者是心脑血管疾病的高危人群，应实施筛查、管理OSAHS，尤其是中、重度OSAHS患者需预防心脑血管并发症的发生。

Abstract:

Objective To investigate the risk of major adverse cardiovascular events(MACE) and all-cause death in type 2 diabetes mellitus(T2DM) with and without obstructive sleep apnea hypopnea syndrome(OSAHS). Methods This cohort study analyzed data from adult T2DM patients hospitalized in the Department of Endocrinology in Shanghai East Hospital between September 2012 and September 2014. According to the sleep apnea-hypopnea index(AHI), the patients were divided into 4 groups: T2DM without OSAHS group(n=55),T2DM with mild OSAHS group(n=94), T2DM with moderate OSAHS group(n=29), and T2DM with severe OSAHS group(n=15). The primary endpoint of this study was to determine the risk of MACE(i.e., non-fatal stroke, non-fatal heart failure, non-fatal myocardial infarction), with secondary outcomes being all-cause mortality. Logistic regression risk models and Kaplan-Meier survival analysis were used to assess the correlation between T2DM combined with OSAHS and clinical events. Results The final analysis used data from 146 subjects. During a median follow-up of 8.0 years(quartile range 5-9 years), 72(49.3%) patients developed MACE and 42(28.8%) died. Logistic regression analysis showed that after adjusting for age, diabetes course, CAD history, hypertension history, and stroke history, moderate and severe OSAHS increased the risk of MACE events in patients with type 2 diabetes(OR=0.07, 95%CI: 0.01-0.66, P=0019; OR=0.08, 95%CI: 0.01-0.86, P=0.037). Kaplan-Meier survival analysis showed no significant difference in all-cause mortality among the 4 groups(log-rank test P=0.124), but the incidence of non-fatal stroke in type 2 diabetes combined with severe OSAHS was significantly higher than that in patients with T2DM alone(log-rank test P=0.016). Conclusion Moderate and severe OSAHS may increase the risk of MACE in patients with T2DM, while severe OSAHS may increase the risk of non-fatal stroke in those patients. OSAHS patients with T2DM are high-risk group of cardiovascular and cerebrovascular diseases. The OSAHS should be screened and managed, especially in moderate and severe OSAHS patients, to prevent the occurrence of cardiovascular and cerebrovascular complications.