马辰星,康向辉(综述),张景义(审校)
(河北联合大学附属开滦总医院 a.内分泌科, b.口腔科, 河北 唐山 063000)
下调空腹血糖截点对早期诊断糖尿病的价值
马辰星a△,康向辉b(综述),张景义a※(审校)
(河北联合大学附属开滦总医院 a.内分泌科, b.口腔科, 河北 唐山 063000)
摘要:近年来,糖尿病发病率逐年上升,且发病年龄有逐年下降的趋势。空腹血糖诊断糖尿病具有快速、经济、简便和易被受检者接受的特点,一直被临床广泛应用。目前,世界卫生组织制订的空腹血糖诊断糖尿病标准依然偏高,导致漏诊率很高。选择一个合理的早期诊断糖尿病的空腹血糖截点成为研究的热点问题。该文就近年来国内外文献对空腹血糖与糖尿病并发症的关系,以及下调空腹血糖截点对早期诊断糖尿病的价值进行了综述。
关键词:糖尿病;空腹血糖;截点;早期诊断
1965年,对Pima印第安人的研究显示,空腹血糖和葡萄糖负荷后2 h血糖(PG 2 h)呈双峰曲线,奠定了糖尿病的诊断标准[1];1979年,美国国家糖尿病数据组制订并发表了糖尿病诊断标准及分型[2];世界卫生组织于1980年对美国国家糖尿病数据组诊断标准进行适当修改后并予以采纳;1985年,世界卫生组织将诊断标准进行修订,并得到广泛认可和应用[3]。经过十多年的临床应用后,许多研究发现空腹血糖≥7.8 mmol/L与PG 2 h≥11.1 mmol/L在糖尿病诊断中缺乏良好的一致性;Pima印第安人等4项流行病学研究资料表明,以PG 2 h≥11.1 mmol/L为糖尿病诊断的金标准,那么最匹配的空腹血糖截点应在6.7~7.0 mmol/L[4~7]。因此,1997年美国糖尿病协会提出空腹血糖诊断截点应该下调至7.0 mmol/L;1999年世界卫生组织正式采纳该建议,形成当今仍在沿用的诊断标准[8]。虽然该标准将空腹血糖仅下调了0.8 mmol/L,但却能使20%的患者免于漏诊,具有划时代的临床意义。现就空腹血糖与糖尿病并发症关系的研究进行予以综述。
1空腹血糖与血管并发症
糖尿病的诊断标准是依据糖尿病性血管病变的发生率制订的[1,4]。因此,空腹血糖与糖尿病性血管并发症之间存在一定的相关性。糖尿病微血管并发症(视网膜病变、肾病等)是致残和降低糖尿病患者生活质量的主要危险因素之一,而80%的2型糖尿病患者死于糖尿病大血管并发症——心血管疾病[9]。早期诊断糖尿病、积极控制血糖对延缓糖尿病慢性并发症具有重要意义,并能真正降低糖尿病血管并发症的致残率和病死率。
1.1空腹血糖与心血管疾病一方面,心血管并发症是导致糖尿病死亡的重要原因之一[10];另一方面,糖尿病又是心血管疾病重要的独立危险因素[11]。众所周知,三酰甘油是预测冠状动脉粥样硬化性心脏病(冠心病)的重要指标,有研究显示, 空腹血糖和空腹三酰甘油呈正相关,并且是餐后三酰甘油的一个重要预测指标[12]。因此,再次印证空腹血糖是冠心病的独立危险因素。另有研究显示,即使正常人群和空腹血糖增高但未达到7.0 mmol/L 的人群,心血管疾病的发生风险与空腹血糖升高也呈线性正相关[13-14]。另外,一项涉及70万非糖尿患者、102个前瞻性研究的荟萃分析结果表明,空腹血糖与心血管疾病的发生风险均呈现一个温和的非线性增加趋势[15]。不但糖尿病早期空腹血糖的增高能够增加心血管疾病病死率[16],而且糖尿病的病程与心血管病死率也呈显著正相关[15]。尽早筛查空腹血糖、早期使血糖控制达标,并尽早干预生活方式,对减少心血管疾病的发生更有意义[17]。
1.2空腹血糖与视网膜病变糖尿病性视网膜病变(diabetic retinopathy, DR)是一种可早期诊断的致盲性眼病。虽然DR发病率很高,但知晓率却很低,就诊率更低,晚期治疗效果不理想,造成了高致盲率,从而给患者带来极大痛苦。我国40岁以上糖尿病患者中DR的患病率约为37%[18];而2005年至2008年,美国≥40岁的成年人DR的患病率约为28.5%[19];在非洲糖尿病患者中DR的患病率为30.2%~31.6%[20]。当糖尿病患者血糖达到一定阈值时,容易发生微血管并发症,从而使DR的发生风险显著增加。Tapp等[21]从澳大利亚随机选择42个地区且年龄≥25岁的成年人,进行视网膜病变的评估,得出结论:当空腹血糖>6.6 mmol/L,DR的患病率已经呈现上升趋势;当空腹血糖>7.1 mmol/L,DR的患病率上升趋势更加显著。Colagiuri等[22]对来自5个国家9项研究的44 623例患者(年龄20~79岁)的可分级视网膜照片数据汇集进行了分析,建议糖尿病的空腹血糖诊断截点应下降为6.5 mmol/L。东亚人口中唯一使用眼科检查的糖尿病研究表明,最佳诊断糖尿病的空腹血糖截点应为 6.4 mmol/L[23]。
1.3空腹血糖与糖尿病肾病糖尿病性肾病是糖尿病最严重的并发症之一,在我国,终末期肾病患者中糖尿病肾病约占15%。众所周知,尿微量白蛋白是糖尿病早期肾脏损害的灵敏指标,也是判断糖尿病性肾病预后的重要指标。Tapp等[21]对某研究人群进行了微量白蛋白尿的评估,结果表明空腹血糖>6.6 mmol/L,糖尿病性肾病的患病率明显上升。
2空腹血糖与PG 2 h
许多研究均显示,空腹血糖与PG 2 h呈线性正相关[4,24-25]。如果以PG 2 h≥11.1 mmol/L为糖尿病诊断的金标准, 那么最匹配的空腹血糖截点为6.4 mmol/L[23]和6.8 mmol/L[4], 均<7.0 mmol/L。也就是说,通过空腹血糖可大概估计其PG 2 h血糖情况。然而,食物血糖生成指数的差异和个人饮食结构的不同,可对PG 2 h造成不同的影响[26-27],致使单纯测量PG 2 h值将导致较大的测量误差。另外,PG 2 h也存在测量不方便、不易被人群接受等缺点,所以PG 2 h不适合作为筛查糖尿病的首要方法。空腹血糖测量方便、经济、易被广大人群接受,并且混杂因素容易控制,不存在饮食差异对血糖测量结果的干扰,结果更快速、可靠。因此,空腹血糖比PG 2 h更适合作为早期筛查及诊断糖尿病的首要手段。
3空腹血糖与糖化血红蛋白
目前,空腹血糖与糖化血红蛋白在糖尿病筛查及诊断意义方面的研究,均以空腹血糖≥7.0 mmol/L为标准,得出糖化血红蛋白诊断糖尿病等效于甚至优于空腹血糖的结果[28-29]。类似研究未阐述血红蛋白病、溶血性疾病或其他与红细胞寿命缩短等对糖化血红蛋白的测定结果会产生何种影响[30-31]。
4空腹血糖截点的争议
虽然空腹血糖≥7.0 mmol/L作为诊断糖尿病的截点在全世界范围内广泛使用,但这个截点仍然不完美,有许多的受检者漏诊。Pima印第安人和美国国家健康及营养调查研究Ⅲ发现,空腹血糖最佳诊断截点为6.8 mmol/L和6.7 mmol/L[4,7]。近年来,一些学者认为,1999年世界卫生组织空腹血糖诊断标准空腹血糖≥7.0 mmol/L偏高,空腹血糖诊断截点降至6.5 mmol/L更为合理[22]。日本久山研究表明,东亚人诊断糖尿病的空腹血糖最佳截点为6.4 mmol/L[23]。韩国一项研究显示,诊断糖尿病的空腹血糖最佳截点是6.1 mmol/L[32]。澳大利亚的研究表明,虽然空腹血糖>6.6 mmol/L,DR的患病率就已经有了较明显地上升,但当空腹血糖>7.1 mmol/L后,DR的患病率才呈现显著上升趋势[21]。同样,我国北京市的一项横断面研究也显示了同样结果,空腹血糖>6.6 mmol/L,DR患病率有所上升,当空腹血糖>7.2 mmol/L后,DR的患病率急剧上升[33]。这两项研究均认为,当前世界卫生组织的诊断截点是合理的。
5小结
近年来,中国的糖尿病患病率大幅增加,有很多患者没有被及时发现,人群中未确诊的糖尿病患者人数众多,估计可达到总患病人数的50%[34]。糖尿病患者在出现临床症状以前有较长的临床前期阶段,而一旦诊断为糖尿病,一部分患者已经合并了糖尿病慢性并发症。目前,甚至有使用现有的医疗计划数据,开发和验证识别2型糖尿病高危个体的预测方程的研究项目[35]。可见,全世界范围内对糖尿病非常重视,糖尿病需要早期筛查、诊断,尽早使血糖控制达标,从而延缓并发症的发生和发展。因此,如何选择一个合理的空腹血糖诊断截点,从而更有效地早期诊断糖尿病成为值得进一步探讨的问题。
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Study on the Value of Down-regulating the Cut-off Point of Fasting Blood Glucose in Early Diagnosis of Diabetes
MAChen-xinga,KANGXiang-huib,ZHANGJing-yia.
(a.DepartmentofEndocrinology,b.DepartmentofStomatology,KailuanGeneralHospitalAffiliatedtoHebeiUnitedUniversity,Tangshan063000,China)
Abstract:In recent years,the incidence of diabetes has been increasing year by year,and the age of onset has a downward trend.Detection of fasting blood glucose has been widely used in clinical to diagnose diabetes due to its characteristics of fast,economical,simple,and easily accepted.Currently,the WHO diagnostic criteria of fasting blood glucose for diabetes remains high,which leads to high rate of misdiagnosis,so choosing a reasonable cut-off point of fasting blood glucose for early diagnosis of diabetes has become a hot research spot.Here is to make a review of relationship between fasting blood glucose and diabetes complications,and the value of down-regulating the cut-off point of fasting blood glucose in early diagnosis of diabetes basing on recent literatures worldwide.
Key words:Diabetes mellitus; Fasting blood glucose; Cut-off point; Early diagnosis
收稿日期:2014-03-19修回日期:2014-07-30编辑:郑雪
doi:10.3969/j.issn.1006-2084.2015.07.043
中图分类号:R587.1
文献标识码:A
文章编号:1006-2084(2015)07-1263-03