Simon Weitzman, MD,MPH 翻译：斯晓燕 妊娠糖尿病诊断的评价 Simon Weitzman, MD,MPH 翻译：斯晓燕

妊娠糖尿病诊断标准的评价 诊断方法和标准 筛检测率 母亲和胎儿结局 In this presentation we will discuss three main subjects: 1. Diagnostic methods and criteria 2. Screening strategies, and 3. Maternal and offspring outcomes with special emphasis on the controversies and methodological problems around each of these subjects 在这次讲座中，我们将讨论三个主要问题： 1.诊断方法和标准 2.筛选策略 3.母亲和婴儿的结果

妊娠糖尿病诊断标准的评价 诊断方法和标准 筛检测率 母亲和胎儿结局 Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy (Metzger BE, Coustan DR Diabetes Care 21 Suppl.2, B1-B167, 1998) . It is generally accepted that the diagnosis of gestational diabetes should be based on blood glucose testing. Two different approaches may be selected for diagnosis: The one-step approach: Consisting on the performance of an oral glucose tolerance test (OGTT) without previous blood glucose testing. This approach is recommended in high risk populations. The two step approach: A first step measuring plasma or serum glucose 1 hour after a 50-gr. oral glucose load (glucose challenge test or GCT), and on those women with values exceeding the diagnostic threshold, a second step performing an oral glucose tolerance test (OGTT). Regardless of the approach used, the diagnosis of GDM is based on the results of the oral glucose tolerance test. 妊娠糖尿病的定义是在妊娠期间发作或首次发现的任何程度的糖耐量受损。 (Metzger BE, Coustan DR Diabetes Care 21 Suppl.2, B1-B167, 1998)这个基于血糖测试的妊娠糖尿病的诊断已经被广泛接受。 有两种不同的方法可以用来诊断： 一步诊断法：以前没有测过血糖的口服糖耐量实验（OGTT） 。这个方法推荐在高危人群中使用。 二步诊断法：第一步在口服50g葡萄糖1个小时后测血浆或血清的葡萄糖水平（葡萄糖负荷试验GCT）,超出正常范围女性在进行第二步口服糖耐量试验（OGTT）。 不管那种方法，诊断妊娠糖尿病都是基于口服糖耐量试验的结果。

妊娠糖尿病的诊断方法 1小时葡萄糖负荷试验（GCT） 口服糖耐量试验（OGTT） 世界卫生组织（WHO） 全国糖尿病资料组（NDDG） Coustan修正方案 The GCT is performed between 24-28 weeks of gestation. A level of > 140 mg/dl is considered abnormal. There are two methods of performing the OGTT, according to the amount of the glucose load. The first, following the WHO recommendation (75 gr.) and the second, as recommended by the National Diabetes Data Group (100 gr.) The next slide presents the different diagnostic criteria for the interpretation of the results of the OGTT 葡萄糖负荷试验在妊娠24－28周进行。血糖> 140 mg/dl 认为是不正常的。根据葡萄糖负荷量的不同，有两种不同的口服糖耐量试验方法。第一种，根据WHO推荐的75g葡萄糖，第二种，根据国家糖尿病治疗组推荐的100g葡萄糖。下一张幻灯片将介绍两者不同的诊断标准。

妊娠糖尿病的诊断 方法 诊断标准(mg/dL) 空腹血糖 1小时 2小时 3小时 WHO（75g） 140 200 NDDG (100g) 105 195 165 145 Coustan (100g) 95 180 155 The WHO uses the 75 gr.oral glucose load, and the diagnosis is based on the fasting and 2-hr blood glucose levels. In contrast, the NDDG and the Coustan modification, uses a 100 gr. glucose load and the diagnosis is based on four measurements (fasting, 1, 2 and 3 hr. glucose levels). It is also important to note, that the diagnostic blood glucose levels are lower by the NDDG than by the WHO method, and even lower by Coustan抯 method. Differences in the diagnostic methods and criteria used in different geographic areas could account, at least in part, for reported differences in the prevalence of GDM. WHO用口服75g葡萄糖负荷，诊断标准是基于空腹血糖和2小时后血糖水平。NDDG和Coustan修正方案用100g葡萄糖负荷，诊断是基于4次血糖值（空腹，1小时，2小时，3小时血糖水平）。值得注意的是NDDG比WHO标准诊断妊娠糖尿病的血糖水平低，Coustan则更低。这些不同的诊断标准在不同的区域使用，至少在某种程度上使得妊娠糖尿病患病率的报道有所不同。

妊娠糖尿病诊断标准的评价 诊断方法和标准 筛检测率 母亲和胎儿结局 Screening implies the application of diagnostic procedures on asymptomatic people in the community, to detect disorders of which they are unaware 筛选是用在社区中无症状人群中的诊断程序，来发现他们还没有意识到的不正常。

妊娠糖尿病的筛选策略 方法 一步法 二步法 We previously described the two approaches for screening recently suggested after the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. However each of these approaches present methodological problems, which are described in the following slides. 我们前面已经介绍过两种筛选的方法，这两种方法在第四届国际妊娠糖尿病会议后被推荐使用。然而，每种方法都有方法学上的问题，我接下来会介绍。

50g葡萄糖负荷试验（>=186mgdL） 敏感性 38.2% 特异性93.3% 阳性预测值78.6% 阴性预测值70.0% Landy et al (1995), in an effort to avoid the two-step testing, suggested that increasing the diagnostic threshold of blood glucose level during the GCT from > 140 mg/dl to ³ 186 mg/dl, could serve as an alternative for the OGTT. Using the OGTT as the gold standard, they showed that the Positive Predictive Value (PPV) of test was 78.6 %, meaning that almost 79% of women with the proposed blood glucose levels during a GCT, were correctly classified as diabetic without the need for further testing. The prevalence of GDM among the population studied by Landy and collaborators was 39.2%. Landy 等人 (1995)为了避免二步法，将诊断值由> 140 mg/dl 提高到 > 186 mg/dl，替代口服糖耐量试验。用以口服糖耐量试验为金标准，他们发现试验的阳性预期值78.6%，这意味着将近79％在糖负荷试验中阳性的女性不需要进一步的检查就可以正确地诊断为妊娠糖尿病。 Landy登人研究人群的妊娠糖尿病的患病率是39.2%。

50g葡萄糖负荷试验（>=186mgdL） 敏感性 38.2% 特异性93.3% 阳性预测值19.5% 阴性预测值97.2% However, when applying the sensitivity and specificity values of the test to a population with a prevalence of GDM of about 4% (as in most reported studies), the Positive Predictive Value of the proposed cut-off blood glucose level was reduced to 19.5%, too low to serve as a single diagnostic test. 然而，当他们把敏感性和特异性用在妊娠糖尿病患病率约4％的人群中去时，阳性预期值就只有19.5%,作为一个独立的诊断试验，这个值太低了。

妊娠糖尿病的筛选策略 人群 群体筛检 高危人群筛检 Universal screening for GDM was recommended in 1985. According to this recommendation, all pregnant women, regardless of the presence of risk factors should be screened for GDM. In 1999, the American Diabetes Association changed the previous recommendations from universal screening to high risk groups screening. High risk women include those age > 25, overweight before pregnancy, members of an ethnic group with a high prevalence of diabetes, having first relatives with diabetes, history of abnormal glucose tolerance and history of poor obstetric outcome. 妊娠糖尿病的群体筛检实在1985年提出来的。根据这个建议，所有妊娠妇女，不管有没有危险因素，都应该进行妊娠糖尿病的筛检。1999年，美国糖尿病协会将群体筛检改为了高危人群的筛检。高危妇女包括：年龄大于25岁，怀孕前超重，是糖尿病患病率高的人种，第一亲属患有糖尿病，糖耐量异常病史，不良生产史。

群体筛检VS高危筛检 群体筛检 57.4%的人同意筛检 27.7%糖负荷试验阳性的人口服糖耐量试验异常 未参加的人有更多的危险因素 高危筛检 可能漏诊40％的妊娠糖尿病 Magee et al (1993) described the advantages and disadvantages of each of the screening strategies. While universal screening was supposed to provide a solution to undiagnosed GDM, it showed that only about half of eligible women would agree to screening, only 27.7% of those with an abnormal GCT had an abnormal OGTT, and those who refused to screening had in fact more risk factors. In contrast, high risk group screening would miss about 40% of GDM women. Magee等（1993）描述了筛选策略各自的优点和缺点。假定群体筛查为未诊断的妊娠糖尿病提供一个解决方案，只有近一半的符合条件的妇女愿意筛查，而糖负荷试验异常的人群中只有27.7%口服糖耐量试验是异常的。事实上拒绝筛查的人却具有更多的危险因素 。相反，高危人群筛查将漏诊40％的妊娠糖尿病妇女。

内盖夫地区的群体筛查 70％的犹太妇女和57％的贝多因妇女同意筛查 49％的妇女进行葡萄糖负荷试验 只有10％的妇女参加口服糖耐量试验 总共未参加的妇女：40％ Data from Holcberg et al (1994) in the Negev region of Israel, confirm the findings by Magee. Although Jewish women had a higher rate of participation than Bedouin women, the overall participation rate was 60%. Holcberg 等人 (1994)在以色列内盖夫地区获得的数据证明了Magee的发现。尽管犹太妇女的参与率比贝多因妇女高，总体的参与率为60％。

妊娠糖尿病诊断标准的评价 诊断方法和标准 筛检测率 母亲和胎儿结局 In this section we will discuss the effect of GDM on the mother and offspring. 这一部分我们将讨论妊娠糖尿病对母亲和胎儿的影响。

妊娠糖尿病对儿童糖尿病发展的影响 动物中高糖血症将影响β细胞的功能 宫内营养剥夺和母体高糖血症增加今后患糖尿病的危险 It was shown in animal experiments that maternal hyperglycemia has deleterious effects on the fetus. Moreover, a body of accumulated evidence supports the hypothesis that maternal hyperglycemia in humans, may lead to intrauterine malnutrition, and as a consequence, an increased risk of diabetes and cardiovascular disease of the offspring in later life. 动物试验表明母亲高糖血症对胎儿有毒性。此外，还有证据支持这个假说：人类母体的高糖血症导致宫内营养不良，结果将增加后代以后得糖尿病和心血管疾病的危险性。

母亲和胎儿的后果 特点 OGTT正常 妊娠糖尿病 大于胎龄儿(%) 34 38 胎龄（周） 39 39.2 住院天数 3.7 3.9 Lucas et al (1993) reported that for selected delivery outcomes, no significant differences were found between GDM and non diabetic women. Lucas 等人 (1993) 报道，妊娠糖尿病妇女和非糖尿病妇女对于选择分娩的结果没有明显的差异。

根据危险因素，妊娠糖尿病妇女围产期特点 特点 危险因素 比值比（95％可信区间） 有 无 剖宫产（％） 38 35 1.6(0.7~3.7) 巨大儿（％） 33 17 2.4(0.9~6.7) 肩难产（％） 7 13 0.5(0.1~2.1) 胰岛素治疗 30 28 1.1(0.4~2.7) In a study by Weeks et al (1994), no differences were found in perinatal characteristics between GDM women with and without additional risk factors, except for an increased trend of macrosomia among newborn of mothers with risk factors. Weeks等人(1994)研究中，妊娠糖尿病妇女不管有没有其它的危险因素，围产期特点没有差异，但是巨大儿有增加的趋势。

In a study by Damm et al (1995), women after a GDM pregnancy were followed for at least 5 years and re-examined to assess their plasma glucose responses after a glucose load. Plasma glucose levels were higher in obese women with previous GDM (Op GDM), than in non-obese women with previous GDM (NOp GDM). Control women had the lowest plasma glucose levels throughout the test. Damm 等人(1995)的研究中，妊娠糖尿病妇女产后至少随访5年，再次监测葡萄糖负荷后的血糖水平。以前有过妊娠糖尿病的妇女中，肥胖妇女的血糖水平比非肥胖妇女高。对照组妇女的血糖水平在实验中一直最低。

In the same study, obese women with previous GDM (Op GDM) showed significantly higher levels of plasma insulin compared with the other two groups. Non-obese women with previous GDM (NOp GDM) had similar responses than control women. These results provide additional support to the relationship between obesity, hyperglycemia and insulin resistance. 在同一个试验中，以前有过妊娠糖尿病的肥胖妇女跟其它两组妇女比血浆胰岛素水平明显更高。以前有过妊娠糖尿病的非肥胖妇女与对照组妇女反应类似。这些结果支持肥胖、高糖血症和胰岛素抵抗之间的关系。

有妊娠糖尿病史妇女此后发生糖尿病的相关因素的对数回归分析 比值比 95％可信区间 诊断时空腹血糖 6.94 1.83~26.24 产后OGTT 0～120分血糖AUC 3.15 1.08~9.23 诊断OGTT 0～60分胰岛素AUC 5.26 1.13~22.50 From the same study, fasting glucose levels at the time of diagnosis of GDM, the area under the curve of glucose levels at postpartum, and the area under the curve of insulin levels at diagnosis of GDM, were independent predictors of the development of diabetes during follow-up. 在同一个试验中，在诊断妊娠糖尿病时空腹血糖水平，产后血糖水平曲线下面积，和诊断妊娠糖尿病时胰岛素水平曲线下面积，在预期此后的糖尿病发展中是对立的。

随访妊娠糖尿病史和健康对照组妇女的糖耐量情况 随访状态 妊娠糖尿病（n＝139） 对照（n＝27） 正常OGTT 64.7(90) 88.9(24) 糖耐量受损 20.1(28) 11.1(3) 2型糖尿病 10.8(15) -- 1型糖尿病 4.3(6) In another study, Damm et al (1994), followed women with previous GDM and non-diabetic controls for the purpose of ascertaining their diabetes status. This slide shows that among women with previous GDM, a significant lower percent had a normal glucose tolerance test at follow-up compared with women without previous GDM (p<0.01). In addition women with previous GDM had an higher percent of OGTT results compatible with the diagnosis of impaired glucose tolerance (IGT) that women without previous GDM. None of the control women developed diabetes during follow-up in contrast to almost 11% of women with previous GDM who developed type 2 diabetes and an additional 4.3% who were diagnosed as type 1 diabetic. 在另外一个研究中， Damm 等人 (1994)随访了有妊娠糖尿病史的妇女和无糖尿病的对照组，来观察她们的糖尿病情况。相比之下，有妊娠糖尿病病史的妇女此后糖耐量试验正常的百分比明显的降低(p<0.01).。此外，有妊娠糖尿病病史的妇女根据OGTT结果诊断糖耐量受损的百分比也更高。在随访中，对照组妇女没有1例发生糖尿病，而有妊娠糖尿病病史的妇女11％发展为2型糖尿病，4.3%诊断为1型糖尿病。

总结（1） J.Nerup 说1型糖尿病是遗传学家的恶梦，同样，妊娠糖尿病是流行病学家的恶梦。对它的定义，最佳诊断方法，诊断标准，确定筛检人群都一直存有争论。

总结（2） 尽管如此，对这些情况的处理已经有了很大改进。除了巨大儿，妊娠糖尿病母亲胎儿的围产期结局已经和非糖尿病母亲的相似了。

总结（3） 有更多的证据表明，有妊娠糖尿病史的妇女得糖尿病(尤其是2型糖尿病)的危险性增加 在肥胖的妊娠糖尿病妇女中，即使是在产后数年，胰岛素抵抗仍然存在。 参考文献 1. American Diabetes Association. Clinical Practice Recommendations. Diabetes Care (Suppl.1) S77-S99, 2000. 2.Magee MS, Walder CE, Benedetti TJ, Knopp RH. Influence of diagnostic criteria on the incidence of gestational diabetes and perinatal morbidity. JAMA 269:609-615, 1993. 3. Blank A, Grave GD, Metzger BE. Effects of gestational diabetes mellitus on perinatal morbidity reassessed. Diabetes Care 18:127-129, 1995 4. Damm P, Kuhl, Hornnes P, Molsted-Pedersen L. A longitudinal study of plasma insulin and glucagon in women with previous gestational diabetes. Diabetes Care 18:654-665, 1995 5. Fraser D, Weitzman S, Leiberman JR, Zmora E, Laron E, Karplus M. Gestational diabetes among Bedouins in southern Israel: comparison of prevalence and neonatal outcomes with the Jewish population. Acta Diabetol 31:78-81, 1994