2. 青岛市预防医学研究院;
3. 青岛市西海岸新区疾病预防控制中心;
4. 山东省疾病预防控制中心;
5. 青岛市内分泌糖尿病医院
心脑血管疾病包括冠心病和缺血性脑卒中,已成为中国人群死因顺位的第一位[1]。80 %心脑血管疾病与血糖异常有关。我国成年人2型糖尿病患者接近1.4亿,还有49 %有糖尿病前期向糖尿病转化的危险[2]。与非糖尿病患者比较,糖尿病患者增加冠心病和脑卒中的发病和死亡风险[3 – 4],空腹血糖和糖耐量受损也增加心血管疾病风险[5 – 6];也有研究得出不同结果[7 – 8]。芬兰和欧洲队列研究证实,糖耐量受损是心脑血管疾病发生和死亡的独立危险因素,与患者后期是否发生糖尿病无相关性[9]。研究表明严格控制空腹血糖和糖化血红蛋白可明显减少慢性微血管并发症,而不能明显降低动脉粥样硬化所致大血管并发症的风险[10]。空腹血糖与心脑血管疾病发生呈J型关系,2 h血糖呈线性关系[11 – 12]。基于糖耐量正常的欧洲人群研究显示,升高2 h血糖增加动脉夹层厚度[13]、糖尿病发病率[14]及心脑血管疾病的发病和死亡风险[15 – 16]。本文拟探讨血糖水平正常人群中,空腹血糖和2 h血糖与心脑血管疾病患病的关联性,旨在为心脑血管疾病危险因素的早期防控提供依据。
1 对象与方法 1.1 对象采用分层随机抽样方法,从山东省青岛市随机抽取3个城市地区(市南、原市北和原四方区)和3个农村地区(原即墨市、原胶南市和原黄岛区),在这6个区市中分别随机抽取3个街道(乡镇),从抽取的街道(乡镇)中分别随机抽取3个居委会(自然村)中35~74岁的常住居民(居住 ≥ 5年)共6 100人作为调查对象[17 – 19]。于2006年2 — 5月完成基线工作,共有5 355人参加调查,应答率为87.8 %。2009 — 2011年采用2006年的抽样方法和调查方案开展第二次横断面调查,7 611人中5 110人参加调查,应答率为67.1 %。调查开始之前,工作人员向调查对象详细解释调查目的,并得到调查对象签订的知情同意书。调查得到青岛市疾病预防控制中心伦理委员会批准。
1.2 一般调查经过统一培训的临床医师和护士指导调查对象完成问卷调查和体格检查。体质指数为体重除以身高的平方(kg/m2),中心性肥胖采用中国肥胖工作组的定义,体质指数 ≥ 28 kg/m2[20]。个人月收入分为低收入者 < 3 000元/月,中等收入3 000~5 999元/月,高收入者 ≥ 6 000元/月。受教育水平分为文盲/小学、初中/高中、大专及以上文化程度3类。吸烟状态分为现在吸烟、不吸烟或已戒烟。饮酒状态分为现在饮酒、不饮酒或已戒酒。高血压采用中华医学会高血压指南2013版标准 [21],调查对象由二级及以上医院的临床医师诊断为高血压,或者接受降压药物治疗,或者收缩压 ≥ 140 mm Hg(1 mm Hg = 0.133 3kPa)和(或)舒张压 ≥ 90 mm Hg。心脑血管疾病主要包括二级及以上医院已确诊的冠心病(心绞痛、急性心肌梗死、慢性充血性心力衰竭、心律失常等)和脑卒中(缺血性脑卒中、出血性脑卒中)等疾病以及自报疾病史或服用药物治疗情况。随机抽取部分自报冠心病或脑卒中患者与青岛市心脑血管监测系统复核,诊断一致率为100 %。
1.3 实验室检查调查对象前日空腹8~10 h,采集清晨空腹血,非糖尿病被调查者服用75 g葡萄糖水,服糖2 h后再次抽血;血液样本放置在肝素钠抗凝管中,– 20 ℃保存。统一运送至实验室采用葡萄糖氧化酶法测定空腹血糖(fasting plasma glucose,FPG)和2 h血糖水平;采用酶法测定甘油三酯、总胆固醇和高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)水平;胰岛素测定采用放射免疫法,以稳态模型法计算胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA-IR)= 空腹胰岛素(mIU/mL) × 空腹血糖(mmol/L)/22.5。HOMA-β 用于评价个体的胰岛 β 细胞功能,计算方法如下:20 × 空腹胰岛素水平(mIU/L)/[空腹血糖水平(mmol/L) – 3.5] [22]。
1.4 高血糖定义和血糖分组糖尿病和糖尿病前期(空腹血糖异常和糖耐量异常)定义依据中华医学会糖尿病学分会2013年的诊断标准[23]。在标准糖耐量试验中,空腹血糖 ≥ 7.0 mmol/L和(或)2 h血糖(2-hour post-load glucose,2hPG)≥11.1 mmol/L和(或)经过三级医院内分泌医生确诊为2型糖尿病,正在服用降糖药物治疗则确诊为糖尿病;糖耐量正常为空腹血糖 < 6.0 mmol/L并且2 h血糖 < 7.8 mmol/L。本研究只包括糖耐量正常的调查对象。根据课题设计和剔除缺失数值的个例,一共有4 307人纳入本研究中。血糖分组根据标准糖耐量试验结果判定,2 h血糖能回到空腹血糖水平设为2hPG ≤ FPG组,2 h血糖高于空腹血糖水平设为2hPG > FPG组。
1.5 统计分析采用一般线性模型分析年龄调整的连续性变量均数,采用方差分析比较不同均数的差异,使用χ2检验比较分类变量差异。采用多因素非条件logistic回归分析,计算血糖水平与心脑血管疾病患病的OR值以及95 % CI,调整因素包括年龄、居住地、研究队列、性别、教育水平、收入水平、工作状态、体质指数、甘油三酯、总胆固醇、HDL-C、吸烟和饮酒状况。以性别、年龄等于60岁、空腹血糖值等于5.6 mmol/L作为界值,对血糖水平与心脑血管疾病的患病率风险进行分层分析。采用SPSS 21.0软件进行统计分析,以P < 0.05为差异有统计学意义。
2 结 果 2.1 一般情况(表1、2)4 307名调查对象中男性1 697人(39.4 %),女性2 610人(60.6 %),平均年龄(48.5 ± 9.8)岁。心脑血管疾病患者1 740例,患病率为40.4 %。与2hPG ≤ FPG组比较,2hPG > FPG组人群年龄较大、体质指数、舒张压、总胆固醇、HDL-C、胰岛素分泌水平较高,差异有统计学意义( P < 0.05)。两组人群心脑血管疾病患病率、蔬菜和水果摄入量差异也有统计学意义( P < 0.05)。
2.2 多因素非条件logistic回归分析(表3)多因素非条件logistic回归分析显示,2hPG > FPG、年龄、体质指数、甘油三酯和饮酒状况可增加心脑血管病风险,OR值及其95 % CI分别为1.210(1.042~1.405)、1.073(1.064~1.082)、1.170(1.144~1.196)、1.396(1.127~1.729)和1.269(1.154~1.396)。分层分析结果显示,以2hPG ≤ FPG为参照,在女性、年龄 < 60岁及FPG < 5.6 mmol/L亚组中,2hPG > FPG组人群心脑血管疾病患病风险增加。将血糖分类变量转化为2 h血糖与空腹血糖差值(2hPG – FPG)的连续性变量,多因素非条件logistic回归分析结果显示,每增加1 mmol/L的2hPG – FPG血糖差值,心脑血管疾病患病率风险增加10.5 %( OR = 1.105,95 % CI = 1.034~1.180);进一步调整蔬菜、水果摄入、体力活动、胰岛素抵抗(HOMA-IR)和胰岛 β 细胞功能(HOMA-β)等混杂因素,2hPG > FPG组人群心脑血管疾病患病风险减弱( OR = 1.263,95 % CI = 1.000~1.591)。
3 讨 论研究显示,与非糖尿病患者比较,糖尿病患者增加冠心病和脑卒中的死亡风险,OR值分别为2.10(1.85~2.39)和2.59(2.16~3.09)[3]。近期研究表明,空腹血糖升高和糖耐量受损均可增加冠心病、脑卒中发病和死亡率,糖耐量受损产生的效应更显著[4 – 5];空腹血糖与心脑血管疾病风险呈J型关系[7, 24],2 h血糖与心脑血管疾病发生呈线性关系[11]。糖耐量受损、血糖的升高增加心脑血管疾病的患病率[25 – 26]。基于亚洲和中国人群的前瞻性研究,进一步证实血糖与心脑血管病发病和死亡相关[27 – 29]。一项台湾地区研究基于空腹血糖和餐后血糖与心血管疾病的死亡分析未得出相同结论[30]。
一项包括19个欧洲成年人研究队列持续9年的随访调查显示,正常糖耐量下,与2hPG ≤ FPG比较,2hPG > FPG分别增加男性25 %和女性60 %的心脑血管疾病死亡率,OR值分别为1.25(1.05~1.50)和1.60(1.03~2.48)[15]。本研究结果显示,2hPG – FPG值每增加1 mmol/L,心脑血管疾病患病率增加10.5 %( OR = 1.105,95 % CI = 1.034~1.180)。本研究结果还显示,调整蔬菜、水果摄入,胰岛素抵抗和胰岛 β 分泌功能等混杂因素后,2hPG > FPG组人群心脑血管患病风险减弱。提示早期胰岛素分泌增加、胰岛素抵抗和炎症反应可能在血糖水平正常时已经出现。2 h血糖能否降至空腹血糖水平,主要借助于胰岛素反应和肝/外周组织的胰岛素敏感性。空腹血糖升高主要归因于肝胰岛素抵抗和第一阶段胰岛素分泌减少,而餐后血糖升高主要与外周胰岛素抵抗和第一、二阶段分泌受损相关 [31 – 32]。正常糖耐量下,2 h血糖升高增加糖尿病和心脑血管疾病风险。肥胖者已经表现出第一阶段胰岛素分泌受损,可能增加糖尿病和代谢综合征风险[33 – 36]。高脂饮食、缺乏体育锻炼等不良生活习惯造成体内脂肪细胞聚集。脂肪细胞炎症反应降低细胞内葡萄糖的利用,导致血糖升高和胰岛素抵抗。研究证实,糖耐量受损患者的运动和饮食干预可以预防和延缓糖尿病发生[37];生活方式干预能够降低41 %心脑血管疾病和29 %的全因死亡率[38]。
综上所述,在血糖正常范围下,较高的2 h血糖可能增加成人心脑血管疾病风险;规律的饮食和体育运动有助于维持血糖和体重在正常水平,从而降低心脑血管疾病的发病风险。
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