Approach
The criteria and approach for diagnosis of gestational diabetes mellitus (GDM) are not universally accepted. It is usually diagnosed at 24-28 weeks of gestation on the basis of elevated plasma glucose levels on glucose tolerance testing. Screening protocols for GDM vary between countries.[41]
Timing of screening for GDM
The American Diabetes Association (ADA) and American Association of Clinical Endocrinology (AACE) both endorse universal screening for GDM in later pregnancy.[1][42] This means that at 24-28 weeks' gestation, all women not known to have diabetes (including high-risk women if the initial testing was normal) should undergo screening with a glucose tolerance test.[1][42] US Preventive Services Task Force guidelines note that testing can occur later if women enter prenatal care after 28 weeks’ gestation.[43] Other guidelines use risk factor-based screening to inform the need for oral glucose tolerance testing at 24-28 weeks’ gestation.[44] Guidelines concur in their recommendation that screening should be undertaken near 24 weeks; this is because treatment of GDM at or after 24 weeks of gestation has been shown to be significantly associated with improved health outcomes (decreased risk of primary cesarean deliveries, shoulder dystocia, macrosomia, large for gestational age, birth injuries, and neonatal intensive care unit admissions).[45] One randomized controlled trial (RCT) found that early GDM diagnosis (prior to 24 weeks of gestation) and immediate treatment demonstrated a modest decrease in a primary composite neonatal outcome that was primarily driven by a reduction in neonatal respiratory distress.[46] Another RCT, however, found that early screening for GDM (at 14-20 weeks’ gestation) in obese women did not improve perinatal outcomes.[47] Due to the lack of consistent evidence to indicate neonatal and maternal benefit from early diagnosis and treatment of GDM, the American College of Obstetricians and Gynecologists (ACOG) does not recommend routine screening for GDM before 24 weeks of gestation.[48]
Testing for GDM
Testing strategies adopt either a one-step method using the 75-g oral glucose tolerance test or a two-step method using a 50-g (nonfasting) glucose load to screen, followed by a 100-g oral glucose tolerance test for those who screen positive.[1]
Testing strategies
Perform a 75-g OGTT, with plasma glucose measurement fasting and at 1 and 2 hours, at 24-28 weeks of gestation in all women not previously diagnosed with overt diabetes
The OGTT should be performed in the morning after an overnight fast of at least 8 hours.
The diagnosis of GDM is made when any one of the following plasma glucose values are exceeded:
Fasting: ≥92 mg/dL (≥5.1 mmol/L)
1 hour: ≥180 mg/dL (≥10.0 mmol/L)
2 hours: ≥153 mg/dL (≥8.5 mmol/L)
Two-step strategy[1]
Perform a 1-hour 50-g glucose load test (GLT) nonfasting.[1][50]
Glucose thresholds of ≥130, 135, or 140 mg/dL (≥7.2, 7.5, or 7.8 mmol/L) on the GLT can be considered abnormal (ACOG recommends that any of these thresholds can be used).[1][51] Lower thresholds are more sensitive than the 140 mg/dL (7.8 mmol/L) threshold (88% to 99% for 130 mg/dL vs. 70% to 88% for 140 mg/dL), but they are less specific and more prone to false-positives.[52] There are no randomized controlled trials of differing thresholds; therefore, it is reasonable for institutions to consider the tradeoffs specific to the population served when determining a cut-off.[1][51]
If glucose levels are greater than the chosen cut-off value on the GLT, a 3-hour 100-g fasting OGTT should be performed.[1]
According to the Carpenter and Coustan criteria (endorsed by the ADA), two or more plasma glucose levels at or above the following thresholds establish diagnosis:[1][51]
Fasting: ≥95 mg/dL (≥5.3 mmol/L)
1 hour: ≥180 mg/dL (≥10.0 mmol/L)
2 hours: ≥155 mg/dL (≥8.6 mmol/L)
3 hours: ≥140 mg/dL (≥7.8 mmol/L)
The older National Diabetes Data Group criteria are stricter and can be used as an alternative to the Carpenter and Coustan criteria. Two or more plasma glucose levels at or above the following thresholds establish diagnosis:[53]
Fasting: ≥105 mg/dL (≥5.8 mmol/L)
1 hour: ≥190 mg/dL (≥10.6 mmol/L)
2 hours: ≥165 mg/dL (≥9.2 mmol/L)
3 hours: ≥145 mg/dL (≥8.0 mmol/L)
The IADPSG recommends a one-step test, while the National Institute of Health and the American College of Obstetricians and Gynecologists (ACOG) recommend a two-step test (although ACOG notes that one elevated value, as opposed to two, may be used for the diagnosis of GDM).[48][49][50][51] The ADA, US Preventive Services Task Force, and AACE recognize that there are data to support both approaches. The ADA notes that the one-step strategy has been adopted internationally as the preferred approach.[1][42][43] Different diagnostic criteria will identify different degrees of maternal hyperglycemia and maternal/fetal risk, leading some experts to debate, and disagree on, optimal strategies for the diagnosis of GDM.[1] A randomized trial which compared the two testing strategies identified twice as many individuals with GDM using the one-step method compared with the two-step method; however, despite more individuals being treated for GDM using the one-step method, there was no difference in pregnancy and perinatal complications.[54] A 2021 US Preventive Services Task Force systematic review concluded that one-step versus two-step screening is associated with increased likelihood of GDM (11.5% vs. 4.9%) but without improved health outcomes.[55] The ADA comments that data comparing population-wide outcomes with one-step versus two-step approaches have been inconsistent to date but that longer-term outcome studies are currently underway.[1]
Symptomatic presentation
Occasionally, women present with overt signs or symptoms of hyperglycemia such as polyuria or polydipsia. This is more likely in women with undiagnosed preexisting diabetes than in those with true GDM. In such a scenario, tests of fasting and/or random glucose levels are appropriate. The ADA advises that the following levels of plasma glucose indicate GDM when obtained in pregnant women after the first trimester:[1]
Fasting glucose: ≥126 mg/dL (≥7.0 mmol/L), confirmed on repeat testing. This is usually used outside of pregnancy but may be useful in patients with signs or symptoms of hyperglycemia.
Random glucose level: ≥200 mg/dL (≥11.1 mmol/L), confirmed on repeat testing (if in the absence of hyperglycemic crisis or classic symptoms of hyperglycemia). This is usually used outside of pregnancy but may be useful in patients with signs or symptoms of hyperglycemia.
Role of hemoglobin A1c (HbA1c) testing
HbA1c, a measure of glycosylated red blood cell hemoglobin, reflects ambient glucose levels over the preceding 2-3 months. The accuracy of HbA1c as a measure of an individual’s level of glycemia is affected primarily by conditions that affect red blood cell survival time or nonenzymatic glycation of hemoglobin.[56] HbA1c levels fall in most women in early pregnancy, which is thought to relate to increased red cell production and a decrease in fasting blood glucose levels. After 20 weeks of gestation, iron deficiency, which becomes increasingly common in later pregnancy, can prolong red cell survival and lead to increased HbA1c levels in some women.[56]
In GDM (or preexisting diabetes at 15 weeks of gestation or later), HbA1c is not sufficiently sensitive to substitute for OGTT as a screening test.[1][57][58] Additionally, as HbA1c represents an integrated measure of glucose, it may not fully capture postprandial hyperglycemia, which drives macrosomia. Thus, although HbA1c may be useful for monitoring, it should be used as a secondary measure of glycemic outcomes in pregnancy, after blood glucose monitoring.[1]
Distinguishing GDM from preexisting (overt) type 2 diabetes
The ongoing epidemic of obesity and diabetes has led to more type 2 diabetes in people of reproductive age, with an increase in the number of pregnant individuals with undiagnosed type 2 diabetes in early pregnancy.[1] Several arguments have been made for identifying and classifying pregnant women with preexisting diabetes as a distinct group from women with GDM:[49]
Increased risk of congenital anomalies in offspring
Risk of diabetes complications (nephropathy and retinopathy) requiring treatment during pregnancy
Need for rapid treatment and close follow-up during pregnancy to ensure prompt restoration of normal glycemia
Need to ensure confirmation and appropriate treatment of diabetes after pregnancy.
Preconception screening for type 2 diabetes
Ideally, undiagnosed type 2 diabetes should be identified preconception in individuals with risk factors or in high-risk populations, as the preconception care of people with preexisting diabetes results in lower HbA1c levels and reduced risk of birth defects, preterm delivery, perinatal mortality, small-for-gestational-age birth weight, and neonatal intensive care unit admission.[1] The ADA recommends preconception screening for undiagnosed type 2 diabetes in all women at increased risk for type 2 diabetes (due to the presence of risk factors as summarized in bullets below) who are planning a pregnancy.[1] The alternative is to perform universal screening on all women of childbearing potential for undiagnosed type 2 diabetes, which may facilitate equitable implementation of screening in populations with a high prevalence of risk factors and/or undiagnosed diabetes.[1]
Standard diagnostic criteria for identifying undiagnosed diabetes preconception are the same as those used in the nonpregnant population; HbA1c, fasting plasma glucose, and plasma glucose 2 hours after 75-g oral glucose are all appropriate screening tests.[1] See Type 2 diabetes in adults.
Screening in early pregnancy
The ADA recommends that, if not screened preconception, patients with risk factors for type 2 diabetes should be screened for preexisting diabetes within the first 15 weeks of pregnancy (i.e., at their first prenatal visit) with an HbA1c or fasting blood sugar using standard diagnostic criteria.[1] It also advises that universal early screening at <15 weeks of gestation (regardless of the presence or absence of risk factors) may be considered, particularly in populations with a high prevalence of risk factors and undiagnosed diabetes in people of childbearing age.[1]
Factors associated with increased risk for diabetes are:[1]
A history of diabetes in a first-degree relative
Overweight or obesity (BMI ≥25 kg/m² [≥23 kg/m² for Asian-Americans])
Physical inactivity
African-American, Latino, Native-American, Asian-American, or Pacific Islander ancestry
History of GDM
Hypertension (≥130/80 mmHg or on therapy for hypertension)
Dyslipidemia (high-density lipoprotein cholesterol <35 mg/dL [0.90 mmol/L] and/or elevated triglycerides >250 mg/dL [2.82 mmol/L])
Cardiovascular disease
Prediabetes (HbA1c ≥5.7% [39 mmol/mol], impaired glucose tolerance or impaired fasting glucose)
Polycystic ovary syndrome
People with HIV, exposure to high-risk medications (such as glucocorticoids, statins, thiazide diuretics, some HIV medications, and second-generation antipsychotic medications), or history of pancreatitis
Other clinical conditions associated with insulin resistance (e.g., acanthosis nigricans).
Standard diagnostic criteria for identifying undiagnosed diabetes in early pregnancy are the same as those used in the nonpregnant population; HbA1c, fasting plasma glucose, and plasma glucose 2 hours after 75-g oral glucose are all appropriate screening tests.[1] Occasionally, women present with overt signs or symptoms of hyperglycemia such as polyuria, polydipsia, or glycosuria. Tests of fasting and/or random glucose levels in such settings are appropriate. See Type 2 diabetes in adults.
Of note, WHO and IADPSG recommend that high-risk women with confirmed fasting glucose levels of ≥126 mg/dL (≥7.0 mmol/L) or random glucose levels ≥200 mg/dL (≥11.1 mmol/L) at any stage of pregnancy (including the first trimester) should receive a diagnosis of preexisting diabetes (usually type 2, although can also be either monogenic diabetes or type 1 diabetes) rather than GDM.[41][49] This differs from the ADA, which defines GDM as diabetes diagnosed in the second or third trimester that was not clearly overt diabetes prior to conception (this definition excludes patients diagnosed in the first trimester because they likely have previously undiagnosed type 2 diabetes).[1]
Early abnormal glucose metabolism
Some at-risk individuals have glucose levels on first trimester screening that, although not meeting criteria for diabetes, are nevertheless too high to be considered normal.
The ADA recommends that before 15 weeks gestation (i.e., at the first prenatal visit) clinicians should screen for abnormal glucose metabolism in order to identify women at higher risk of adverse pregnancy and neonatal outcomes, those who are more likely to need insulin, and those who are more likely to develop GDM later in pregnancy.[1] Early abnormal glucose metabolism has also been associated with an increased risk of incident diabetes postpartum.[59]
The ADA defines abnormal glucose metabolism as:[1]
Fasting glucose of 110-125 mg/dL (6.1 mmol/L; impaired fasting glucose) or
HbA1c of 5.9% to 6.4% (41-47 mmol/mol)
Additionally, impaired glucose tolerance (IGT) is suggested by 2-hour oral glucose tolerance test (OGTT) values of 140 mg/dL to 199 mg/dL (7.8 mmol/L to 11.0 mmol/L).[60]
Current guidelines do not clearly classify women with abnormal glucose metabolism in the first trimester as having GDM, as there are only limited data demonstrating improved outcomes with treatment before the third trimester.[60]
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