Diagnosis of GDM
Gestational diabetes mellitus (GDM), initially defined as glucose tolerance presenting in pregnancy but remitting thereafter, is currently defined as any glucose intolerance with onset or first recognition during pregnancy. The newer definition was introduced to allow for unrecognised pre-existing diabetes. Although there is no question that hyperglycemia in pregnancy is associated with worse fetal outcomes, controversy persists as to the best way of defining hyperglycemia, timing of testing, and the optimal cut-off point for intervention. The American College of Obstetricians and Gynecologists (ACOG) advocates a screening glucose challenge for all women in the second trimester, whereas the American Diabetes Association (ADA) and the International Association of Diabetes and Pregnancy Study Group (IADPSG) recommend first trimester screening for women at high risk of diabetes, followed by universal glucose tolerance testing at 24-28 weeks. The ADA/IADPSG glucose criteria for the diagnosis of GDM by the OGTT are 5.1 mmol/l fasting, 10 mmol/l at 1 hour and 8.5 mmol/l at 2 hours. Recently, The Endocrine Society introduced recommendations for first trimester screening, defining GDM as a fasting blood glucose of 5.1-6.9 mmol/l, while endorsing the ADA/IADPSG second trimester diagnostic criteria. Critics of these criteria maintain that they result in overdiagnosis of GDM and unnecessary interventions, and the controversy seems set to continue.
Gestational diabetes mellitus (GDM) was initially defined by O’Sullivan and Mahan in 1964 as “transient abnormalities of glucose tolerance that develop during pregnancy” and resolve post-partum. Currently, GDM is defined more loosely as any glucose intolerance with onset or first recognition during pregnancy. This newer definition removes the need for knowledge of normal pre-pregnancy glucose tolerance, as well as the need to define reversion to normal glucose tolerance post-partum.
This change recognizes "real-world" issues: the fact that diabetes is initially identified during pregnancy does not rule out the possibility of prior ‘dysglycemia’ (including overt pre-gestational diabetes), which is only discovered by formal testing during pregnancy3. Due to the increased prevalence of obesity and type 2 diabetes, it is now well recognized that women of child-bearing age may have unrecognized type 2 diabetes, and thus the new, more pragmatic American Diabetes Association (ADA) and International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines for screening of diabetes in pregnancy take that into account, advocating first trimester screening for diabetes in high risk women, and recommending use of the term “overt diabetes”, rather than “GDM”, if the findings are positive3.
The timing and tests used for screening and diagnosis of GDM in pregnancy remain subject to controversy. The initial screening test proposed by O’Sullivan was conducted in the second trimester and involved a non-fasting 50g glucose “challenge” followed by measurement of the plasma glucose one hour later. A positive result was a one-hour glucose >7.8 mmol/L. This test was typically offered at 24-28 weeks’ gestation and, if equivocal, was followed by a confirmatory standardized three-hour 100g OGTT to establish the diagnosis. This “two-step approach” is still endorsed by the American College of Obstetricians and Gynecologists (ACOG) .
In contrast, the ADA, in concert with the IADPSG, issued modified guidelines for the diagnosis of diabetes in pregnancy. They aimed to address concerns related to the increased prevalence of overt type 2 diabetes in younger populations, as well as concerns about complications of pregnancy even with mild degrees of hyperglycemia, as shown by the recent “Hyperglycemia and Pregnancy Outcomes Study” (HAPO) study .
These new guidelines recommend first trimester screening for high risk women (Table 1). The diagnosis of pre-gestational diabetes is made either by finding glycated hemoglobin level ≥ 6.5% (47.5 mmol/mol) and/or fasting blood glucose (FBG)≥7 mmol/L, or a positive 75-g, two-hour oral glucose tolerance test (OGTT) using standard (non-pregnancy) thresholds (i.e fasting glucose ≥7 mmo/L or 2hr glucose ≥11 mmol/L).
Since first trimester nausea and morning sickness are problematic for many women, use of a non-fasting test (HbA1c) to screen for pre-gestational diabetes is an attractive option. For women not considered high risk (i.e not meeting any of the criteria outlined in Table 1) and/or found to be euglycemic at the first trimester testing, the ADA/IADPSG still recommend universal screening for GDM at 24-28 weeks, but using a one-step, 75-g two-hour OGTT. The following thresholds are used for positive diagnosis (any individual abnormal value is considered diagnostic of GDM): fasting blood glucose: ≥5.1 mmol/L; 1 h: ≥10.0 mmol/L; 2 h: ≥8.5 mmol/L (Table 2). These revised, lower cut-points were derived from the HAPO study, and represent an odds ratio for adverse pregnancy outcomes of 1.75 in comparison with euglycemic women 3,5.
More recently, the Endocrine Society issued their own guidelines advocating screening for dysglycemia at the first trimester of pregnancy and defining GDM as a fasting BG of 5.1-6.9 mmol/l. Women with a fasting BG <5.1 mmol/l are re-tested at the second trimester, where the ADA/IADPSG criteria are endorsed (Table 2), with the addition of a "overt diabetes category" should the following, higher thresholds be attained: Fasting BG ≥7 mmol/l or 2h BG ≥ 11.1 mmol/l.
In conclusion, the demonstration in the HAPO study that in pregnancy, even mild degrees of ‘dysglycemia’ are associated with adverse outcomes, coupled with the greatly increased world-wide prevalence of Type 2 diabetes, emphasize the importance of definition, screening, and detection. Internationally agreed criteria are highly desirable to define standards and goals, and to enable meaningful comparisons of data from different sources. Inevitably, however, the increasing choice of tests available, their timing, and resource considerations mean that a lively debate will continue.
Table 1: Who should be screened early in pregnancy for pre-gestational diabetes? (ADA (and IADPSG) recommendations, adapted from Ref 3)
|BMI ≥ 25 kg/m2 AND any of the following:|
|- Physical inactivity|
|- First-degree relative with diabetes|
|- High-risk race/ethnicity|
|African American, Latino, Native American, Asian American, Pacific Islander|
|Blood pressure>140/90 mmHg or on treatment for HTN|
|- A1C ≥5.5% (36.6 mmol/mol), IGT, IFG on previous testing|
|- Delivered a baby weighing>9 pounds (4.1 kg) or previously diagnosed with GDM|
|Clinical conditions associated with insulin resistance|
|Polycystic Ovarian Syndrome|
|- History of CVD|
Table 2: Screening for GDM during the second trimester: ADA/IADPSG vs ACOG guidelines. Note, ADA/IADPSG also recommends earlier screening for high-risk women, see Table 1. (Adapted from Refs. 3 and 4)
|ADA/IADPSG recommendations||ACOG Recommendations|
|24-28 weeks, Universal||24-28 weeks, Universal|
|75 g OGTT after overnight fast||50g, 1h screening test|
|Any ONE of the following:||If 1h BG>7.5-7.8 mmol/L, proceed with diagnostic test (100g, 3h test)|
|* FBG≥5.1 mmol/L||Two or more abnormal values for positive diagnosis:|
|* 1h≥10.0 mmol/L||* FBG ≥ 5.3 mmol/L|
|* 2h≥8.5 mmol/L||* 1h ≥ 10.0 mmol/L|
|* 2h ≥ 8.6 mmo/L|
|* 3h ≥ 7.8 mmol/L|
^ O'Sullivan, J.B., Gestational Diabetes and its Significance. Early Diabetes, ed. C.H. Camerini-Davalos R. 1970, New YAcademic Press.
^ O'Sullivan, J.B. and C.M. Mahan, Criteria for the Oral Glucose Tolerance Test in Pregnancy. Diabetes 13:278-85, 1964
^ American Diabetes Association. Standards of Medical Care in Diabetes—2013. Diabetes Care 36:S67-S74, 2013
^ ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 30, September 2001 (replaces Technical Bulletin Number 200, December 1994). Gestational diabetes. Obstet Gynecol, 98:525-38, 2001
^ HAPO Study Cooperative Research Group, Metzger BE et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 358:1991-2002, 2008.
^ Blumer I et al. Diabetes and pregnancy: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013 Nov;98(11):4227-49. doi: 10.1210/jc.2013-2465.