没有公认的诊断标准。检查策略包括使用 75 g 口服葡萄糖耐量试验的一步式方法或使用 50 g(非禁食)葡萄糖负荷的两步式方法实施筛查,然后对筛查阳性的患者实施 100 g 口服葡萄糖耐量试验。
筛查:建议对显性糖尿病风险增加的妇女实施筛查
国际糖尿病与妊娠研究组 (International Association of Diabetes and Pregnancy Study Groups, IADPSG) 标准(美国糖尿病协会 [ADA] 认可)推荐:在首次产前就诊时,使用标准的诊断标准,对 2 型糖尿病风险升高的患者进行糖尿病筛查。[2]American Diabetes Association. Standards of medical care in diabetes - 2018. Diabetes Care. 2018 Jan 1;41 Suppl 1:S1-159.http://care.diabetesjournals.org/content/41/Supplement_1[31]Metzger BE, Gabbe SG, Persson B, et al; International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010 Mar;33(3):676-82.http://care.diabetesjournals.org/content/33/3/676.long 可使糖尿病风险增加的因素包括体重指数 (BMI) >25 kg/m²(或者在亚裔美国人中>23 kg/m²),加上一个额外的危险因素,例如糖尿病家族史、妊娠期糖尿病 (GDM) 个人病史、多囊卵巢综合征、非白人血统以及既往检查时空腹血糖受损 (IFG) 或糖耐量减低 (IGT)。[2]American Diabetes Association. Standards of medical care in diabetes - 2018. Diabetes Care. 2018 Jan 1;41 Suppl 1:S1-159.http://care.diabetesjournals.org/content/41/Supplement_1
妊娠糖尿病高风险患者(肥胖、GDM 个人史或前一个孩子为巨大胎儿、多囊卵巢综合征、糖尿、2 型糖尿病家族史),也应当在首次产前就诊时接受葡萄糖耐量试验。[2]American Diabetes Association. Standards of medical care in diabetes - 2018. Diabetes Care. 2018 Jan 1;41 Suppl 1:S1-159.http://care.diabetesjournals.org/content/41/Supplement_1[31]Metzger BE, Gabbe SG, Persson B, et al; International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010 Mar;33(3):676-82.http://care.diabetesjournals.org/content/33/3/676.long
妇女偶尔存在显著的高血糖症体征或症状,例如多尿、多饮或糖尿。在这种情况下,应当检查空腹和/或随机血糖水平。 ADA 和 IADPSG 建议,在妊娠早期,经过确认的空腹血糖水平≥7.0 mmol/L (≥126 mg/dL) 或随机血糖水平≥11.1 mmol/L (≥200 mg/dL) 的高风险女性,应当诊断为显性糖尿病(而非妊娠糖尿病)。[2]American Diabetes Association. Standards of medical care in diabetes - 2018. Diabetes Care. 2018 Jan 1;41 Suppl 1:S1-159.http://care.diabetesjournals.org/content/41/Supplement_1[31]Metzger BE, Gabbe SG, Persson B, et al; International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010 Mar;33(3):676-82.http://care.diabetesjournals.org/content/33/3/676.long
一些有风险的个体在妊娠早期筛查时的血糖水平尽管不符合糖尿病标准,但是过高也不能被认定为正常。将这些患者定义为 IFG(空腹血浆葡萄糖水平 5.6 mmol/L 至 6.9 mmol/L [100 mg/dL 至 125 mg/dL])或 IGT(2 小时口服葡萄糖耐量试验 [OGTT] 值为 7.8 mmol/L 至 11.0 mmol/L [140 mg/dL 至 199 mg/dL])。 HbA1c 为 5.7% 至 6.4%(前期糖尿病)的患者,也被视为风险增加。[32]Hughes RC, Moore MP, Gullam JE, et al. An early pregnancy HbA1c ≥5.9% (41 mmol/mol) is optimal for detecting diabetes and identifies women at increased risk of adverse pregnancy outcomes. Diabetes Care. 2014 Nov;37(11):2953-9.http://care.diabetesjournals.org/content/37/11/2953.long 现行指南没有将在妊娠早期存在 IFG、IGT 或糖尿病前期的女性明确归类为患有 GDM;然而,现有数据提示,这些患者在妊娠后期发生需要胰岛素治疗的 GDM 的风险较高。[32]Hughes RC, Moore MP, Gullam JE, et al. An early pregnancy HbA1c ≥5.9% (41 mmol/mol) is optimal for detecting diabetes and identifies women at increased risk of adverse pregnancy outcomes. Diabetes Care. 2014 Nov;37(11):2953-9.http://care.diabetesjournals.org/content/37/11/2953.long
筛查:建议对不具备显性糖尿病高风险的妇女实施筛查
因为在实践中,很少有女性符合所有低风险标准,因此许多医生对所有女性实施妊娠糖尿病筛查。[33]US Preventive Services Task Force. Screening for gestational diabetes mellitus. Dec 2016 [internet publication].https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/gestational-diabetes-mellitus-screening ADA 指南建议一步或两步式筛查方法。[2]American Diabetes Association. Standards of medical care in diabetes - 2018. Diabetes Care. 2018 Jan 1;41 Suppl 1:S1-159.http://care.diabetesjournals.org/content/41/Supplement_1
在孕 24 至 28 周,所有非已知患糖尿病的妇女(包括初次检查正常的高危妇女)应当接受葡萄糖耐量试验筛查。可供选择的方式为:
IADPSG 建议一步式检测,[31]Metzger BE, Gabbe SG, Persson B, et al; International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010 Mar;33(3):676-82.http://care.diabetesjournals.org/content/33/3/676.long 但美国国立卫生研究院 (National Institute of Health) 和美国妇产科学院 (American Congress of Obstetricians and Gynecologists, AGOG) 推荐两步法试验。[34]American College of Obstetricians and Gynecologists: Committee on Practice Bulletins - Obstetrics. ACOG practice bulletin No. 180: gestational diabetes mellitus. Obstet Gynecol. 2017 Jul;130(1):e17-37.[35]Vandorsten JP, Dodson WC, Espeland MA, et al. NIH consensus development conference: diagnosing gestational diabetes mellitus. NIH Consens State Sci Statements. 2013 Mar 6;29(1):1-31. 美国糖尿病学会 (ADA) 认为两种方式均有数据支持。[2]American Diabetes Association. Standards of medical care in diabetes - 2018. Diabetes Care. 2018 Jan 1;41 Suppl 1:S1-159.http://care.diabetesjournals.org/content/41/Supplement_1
ADA 推荐,实施 75 g OGTT 时,如果结果异常,可诊断妊娠糖尿病。对于这些患者,现行的筛查和诊断策略如下:[2]American Diabetes Association. Standards of medical care in diabetes - 2018. Diabetes Care. 2018 Jan 1;41 Suppl 1:S1-159.http://care.diabetesjournals.org/content/41/Supplement_1
使用两步式方法时,女性接受 1 小时 50 g 葡萄糖负荷试验,不需要禁食。[2]American Diabetes Association. Standards of medical care in diabetes - 2018. Diabetes Care. 2018 Jan 1;41 Suppl 1:S1-159.http://care.diabetesjournals.org/content/41/Supplement_1[35]Vandorsten JP, Dodson WC, Espeland MA, et al. NIH consensus development conference: diagnosing gestational diabetes mellitus. NIH Consens State Sci Statements. 2013 Mar 6;29(1):1-31. 血糖阈值为 7.2 或 7.8 mmol/L(130 或 140 mg/dL)被视为异常。7.2 mmol/L (130 mg/dL) 水平比 7.8 mmol/L (140 mg/dL) 的阈值更敏感(分别为 90% 与 80%),但特异性较差,更容易产生假阳性。[2]American Diabetes Association. Standards of medical care in diabetes - 2018. Diabetes Care. 2018 Jan 1;41 Suppl 1:S1-159.http://care.diabetesjournals.org/content/41/Supplement_1[34]American College of Obstetricians and Gynecologists: Committee on Practice Bulletins - Obstetrics. ACOG practice bulletin No. 180: gestational diabetes mellitus. Obstet Gynecol. 2017 Jul;130(1):e17-37.
如果血糖水平≥7.8 mmol/L (≥140 mg/dL),则进行 3 小时 100 g OGTT。[2]American Diabetes Association. Standards of medical care in diabetes - 2018. Diabetes Care. 2018 Jan 1;41 Suppl 1:S1-159.http://care.diabetesjournals.org/content/41/Supplement_1 在患者空腹时实施这项检测。如果两个或更多血糖值达到或超过下列阈值即可确诊。
在妊娠早期过后的孕妇中,随机或空腹测定的血浆葡萄糖水平升高到足以考虑提示妊娠糖尿病(这个临界值通常用于超出妊娠范围以诊断糖尿病,对有高血糖体征或症状的妊娠患者也可能有用):[2]American Diabetes Association. Standards of medical care in diabetes - 2018. Diabetes Care. 2018 Jan 1;41 Suppl 1:S1-159.http://care.diabetesjournals.org/content/41/Supplement_1
其他筛查指南
除了 ADA 的建议外,还有其他几份指南可用。[31]Metzger BE, Gabbe SG, Persson B, et al; International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010 Mar;33(3):676-82.http://care.diabetesjournals.org/content/33/3/676.long[36]Mulholland C, Njoroge T, Mersereau P, et al. Comparison of guidelines available in the United States for diagnosis and management of diabetes before, during, and after pregnancy. J Womens Health (Larchmt). 2007 Jul-Aug;16(6):790-801.[37]Royal College of Obstetricians and Gynaecologists. Scientific Impact Paper no. 23. Diagnosis and treatment of gestational diabetes. Jan 2011 [internet publication].https://www.rcog.org.uk/globalassets/documents/guidelines/scientific-impact-papers/sip_23.pdf
WHO 建议禁食 8 至 14 小时后实施 75 g OGTT。[38]World Health Organization, International Diabetes Federation. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation. 2006 [internet publication].http://www.who.int/diabetes/publications/Definition%20and%20diagnosis%20of%20diabetes_new.pdf 若孕妇满足非妊娠人群的 WHO 糖耐量减低标准(空腹静脉血糖<7.0 mmol/L [<126 mg/dL],伴服糖后 2 小时血糖水平≥7.8 mmol/L [≥140 mg/dL] 但<11.1 mmol/L [<200 mg/dL])或 WHO 糖尿病标准(空腹静脉血糖≥7.0 mmol/L [≥126 mg/dL] 或服糖后 2 小时血糖≥11.1 mmol/L [≥200 mg/dL]),则 WHO 指南将这些孕妇归类为患有妊娠期糖尿病 (GDM)。建议在妊娠早期筛查高危孕妇,在 24 至 28 周开展普遍筛查。高危女性符合下列一个或多个特征:
年龄较大(> 40 岁)
大于胎龄儿病史
血糖异常既往史
高危族裔
空腹或随机血糖升高。
英国 NICE 指南建议对有下列任何一个妊娠糖尿病危险因素的女性开展筛查:[4]National Institute for Health and Care Excellence. Diabetes in pregnancy: management from preconception to the postnatal period. Aug 2015 [internet publication].http://www.nice.org.uk/guidance/ng3
体重指数 (BMI)>30 kg/m²
既往巨大婴儿体重 > 4.5 kg
既往患有妊娠糖尿病
糖尿病家族史(一级亲属患有糖尿病)
祖籍为糖尿病高患病率地区
NICE 指南建议在孕 24 至 28 周时使用 WHO 制定的 OGTT 标准开展筛查,但既往患过妊娠糖尿病的女性除外,她们应当在 16 至 18 周筛查。如果首次 OGTT 正常,则在 28 周时再次筛查。[4]National Institute for Health and Care Excellence. Diabetes in pregnancy: management from preconception to the postnatal period. Aug 2015 [internet publication].http://www.nice.org.uk/guidance/ng3
国际妇产科联盟 (International Federation of Gynecology and Obstetrics) 推荐使用一步式方法进行普遍筛查,根据 WHO 或 IADPSG 临界值确诊 GDM。[39]Hod M, Kapur A, Sacks DA, et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on gestational diabetes mellitus: a pragmatic guide for diagnosis, management, and care. Int J Gynaecol Obstet. 2015 Oct;131 Suppl 3:S173-211.http://onlinelibrary.wiley.com/doi/10.1016/S0020-7292(15)30033-3/epdf
HbA1c
HbA1c 是糖基化红细胞血红蛋白的值,反映了近 2 至 3 个月内的血糖水平。
在已经患有糖尿病的女性中,孕前 HbA1c 水平升高与胎儿异常相关。在计划妊娠之前,血糖控制应当尽可能接近正常(HbA1c 不超过参考范围正常值上限 10 mmol/mol [1%])。[2]American Diabetes Association. Standards of medical care in diabetes - 2018. Diabetes Care. 2018 Jan 1;41 Suppl 1:S1-159.http://care.diabetesjournals.org/content/41/Supplement_1
在妊娠糖尿病中,HbA1c 不够敏感,不能作为筛查试验替代 OGTT。[40]Homko CJ, Khandelwal M. Glucose monitoring and insulin therapy during pregnancy. Obstet Gynecol Clin North Am. 1996 Mar;23(1):47-74.[41]Agarwal MM, Dhatt GS, Punnose J, et al. Gestational diabetes: a reappraisal of HBA1c as a screening test. Acta Obstet Gynecol Scand. 2005 Dec;84(12):1159-63.[42]Agarwal MM, Hughes PF, Punnose J, et al. Gestational diabetes screening of a multiethnic, high-risk population using glycated proteins. Diabetes Res Clin Pract. 2001 Jan;51(1):67-73.诊断:有中等质量证据表明,HbA1c 不具有足够的敏感度和特异度,无法准确诊断妊娠糖尿病,与 75 g 葡萄糖耐量试验 (GTT) 相比,接受者操作特征曲线下面积只有 0.54。[41]Agarwal MM, Dhatt GS, Punnose J, et al. Gestational diabetes: a reappraisal of HBA1c as a screening test. Acta Obstet Gynecol Scand. 2005 Dec;84(12):1159-63. 一项单独的研究发现,与 100 g GTT 相比,孤立的果糖胺指标可达到的敏感度为 92.2%,作为筛查工具不足够敏感,但 HbA1c 与果糖胺联合评估,敏感度为 96.1%,如果使用,可以使接近 40% 的患者免除口服葡萄糖耐量试验。[42]Agarwal MM, Hughes PF, Punnose J, et al. Gestational diabetes screening of a multiethnic, high-risk population using glycated proteins. Diabetes Res Clin Pract. 2001 Jan;51(1):67-73.受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。
既往血糖异常的延长效应限制了血红蛋白 A1c 用于妊娠,此时的目标是迅速改善血糖控制,因而需要直接监测血糖。
静脉穿刺和抽血的动画演示