American Diabetes Association “Standards of Medical Care—2020 for Gestational Diabetes Mellitus”: A Critical Appraisal

Periodic update Guidelines are formulated on the basis of available evidence that keeps changing with time. This means that guidelines should be updated at periodic intervals. Glyburide (glibenclamide) is a good example of this need. While glyburide was initially preferred over metformin as an alternative to insulin, a 2015 meta-analysis and systematic review suggested that it was associated with a higher rate of neonatal hypoglycemia and macrosomia than insulin or metformin [4]. On the basis of the new data, its role in management of GDM was downplayed in the subsequent ADA guidelines [5]. On the other hand, the Endocrine Society guidelines, which have not been updated since 2013, continue to refer glyburide as the preferred agent [6]. Thus, a regular update of the ADA guidance document in a time-bound manner (released every January as a special supplement) is one of its main strengths.

Flexibility in approach to reflect prevailing practices In the USA, the National Institutes of Health (NIH) and American College of Obstetrics and Gynecology (ACOG) still recommend the use of a two-step strategy for screening and diagnosis of GDM [7, 8]. This involves an initial screening with 50-g glucose challenge followed by a 3-h 100-g oral glucose tolerance test (OGTT) interpreted according to Carpenter and Coustan criteria in those who are screen positive. In 2011, ADA modified its recommendation to one-step diagnosis of GDM using International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria instead of the two-step strategy proposed earlier [9]. However, in 2014, ADA amended its viewpoint and recommended the use of either strategy for diagnosis of GDM, while stating that different strategies will identify different degrees of hyperglycemia severity and maternal and fetal risks [10]. In a similar vein, Diabetes Canada Clinical Practice Guidelines identify a preferred (two-step) and an alternate (one-step) screening strategy for GDM [11]. Such an inclusive approach increases generalizability, avoids conflicts, and respects varied viewpoints, especially when the evidence is equivocal.

Clear approach for prenatal testing and postpartum follow-up ADA guidelines clearly highlight the timing and nature of tests to be performed during pregnancy and in the postpartum period. There is an emphasis on testing for hyperglycemia at the first prenatal visit in high-risk women using standard diagnostic criteria [fasting plasma glucose and/or 2-h plasma glucose post 75-g glucose load and/or hemoglobin A1c (HbA1c)]. This is in response to the increasing burden of undiagnosed diabetes in women of reproductive age worldwide. Screening for GDM at 24–28 weeks is appropriately recommended for women found to have normoglycemia on the initial visit and in those who missed the test in earlier visit. There are data on the increased risk of adverse glycemic outcomes among women with GDM [12‐15] and the guidelines aptly bring about the need for testing these high-risk women at 4–12 weeks postpartum using a 75-g OGTT. The preference for OGTT over HbA1c is based upon the increased sensitivity of the former and possibility of misleading results with the latter within 3 months after the delivery. Considering an increase in the lifetime risk for developing diabetes among women with GDM, further testing is recommended in those with normal postpartum OGTT every 1–3 years. The assessment may be performed using annual fasting plasma glucose, annual HbA1c, or three-yearly 75-g OGTT. Finally, there is a clear emphasis on the importance of breastfeeding, contraception, and preconceptional evaluation in women with a history of GDM.

Time of pregnancy for the diagnosis of GDM ADA guidelines define GDM as “diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation”. ADA clearly states that IADPSG criteria as well as the diagnostic criteria used in the two-step approach were not derived from women enrolled in the first half of pregnancy. In light of this observation, the rationale behind extending the diagnostic criteria to the entire second trimester (13–28 weeks) and selectively excluding the first trimester (< 13 weeks) is not clear. World Health Organization (WHO) 2013 and FIGO (International Federation of Gynecology and Obstetrics) guidelines recommend diagnosis of GDM if the IADPSG criteria are fulfilled anytime during the pregnancy [16, 17]. Clearly, more consensus is needed on the applicability of a diagnosis of GDM during early pregnancy.

Use of term “overt diabetes prior to gestation” in the GDM definition In 2010, an IADPSG consensus panel introduced a new term, “overt diabetes during pregnancy”, which demarcated women with GDM from those with hyperglycemia of greater severity [18]. This term was used to label women who were diagnosed with diabetes (as per standard criteria for diagnosis outside the pregnancy) for the first time during the pregnancy. A similar definition was used by WHO 2013 guidelines, albeit with a different term “diabetes in pregnancy” [16]. The term “overt diabetes prior to gestation” used in the ADA definition (see above) is not in alignment with our current understanding of GDM and should have been “overt diabetes during gestation”.

Use of the term “prediabetes” in the context of pregnancy One of the recommendations states “test for undiagnosed prediabetes and diabetes at the first prenatal visit in those with risk factors using standard diagnostic criteria”. The use of term “prediabetes” in pregnant women is not backed by scientific evidence. This term has never been used previously by any other organizations such as WHO and IADPSG [16, 18]. Further, in the accompanying text, the guidelines recommend that women with “intermediate hyperglycemia” at the first prenatal visit should be diagnosed and treated as GDM. Does this mean that the terms GDM and prediabetes could be used interchangeably?

Inconsistent use of terminology While the 2019 ADA document used the term “pre-existing pre-gestational diabetes” for values clearly indicative of diabetes, this has been replaced by another term “diabetes complicating pregnancy” in the current version [3, 19]. It is not clear whether this term has been used in the same context or has been intended to include the subgroup of women with hyperglycemia meeting threshold of overt diabetes in pregnancy, but without known pre-existing diabetes.

Definition of intermediate hyperglycemia The usage of term “prediabetes” for intermediate hyperglycemia detected at the first prenatal visit should be strictly avoided because of lack of scientific evidence. Besides, it is not appropriate to use terms “prediabetes” and “GDM” interchangeably for the following reasons: (a) Diagnostic thresholds for these two conditions on a 75-g OGTT are entirely different—fasting and 2-h plasma glucose of ≥ 5.1 mmol/L and ≥ 8.5 mmol/L for GDM, and ≥ 5.6 mmol/L and ≥ 7.8 mmol/L for prediabetes [3, 18]. Moreover, while HbA1c can be used for diagnosis of prediabetes according to ADA criteria, the same is not true for GDM. (b) Prediabetes has only been defined outside the pregnancy and is largely managed with dietary and lifestyle modifications. On the other hand, the implications for even milder forms of hyperglycemia during pregnancy are significant and a sizeable proportion (around 20%) of women with GDM warrant pharmacotherapy [14].

We, therefore, agree with the WHO classification which avoids the use of such confusing terminology and identifies hyperglycemia during pregnancy into two broad categories—gestational diabetes and diabetes in pregnancy.