PregnancyDM S2 Screening

Identification, Screening, and Diagnosis of Diabetes in Pregnancy

GDM Definition, Etiology, Risk Factors, and Pathophysiology

Definition

Gestational diabetes mellitus (GDM) has been defined as any degree of carbohydrate intolerance with onset during pregnancy. This definition is a misnomer in that it includes unrecognized overt diabetes that may have been present prior to pregnancy as well as hyperglycemia that develops during pregnancy. Preexisting type 2 diabetes can often present as severe hyperglycemia during pregnancy.

Etiology

GDM is due to hormonally induced insulin resistance, which leads to hyperglycemia and eventually diabetes.

Risk Factors

The following are risk factors for GDM:1,2

  • Obesity
  • Previous history of GDM
  • Prior delivery of a large baby (>9 lbs)
  • Glycosuria
  • Family history of diabetes in a first-degree relative

Pathophysiology

During pregnancy, insulin resistance develops as a normal response to the placental secretion of anti-insulin hormones, such as cortisol, growth hormone, human placental lactogen, progesterone, and tumor necrosis factor alpha (TNF-α).3

In late pregnancy, to meet the glycemic demands of the growing fetus, maternal hepatic glucose production increases by 15% to 30%.3

In some patients, pancreatic beta-cell dysfunction develops, and the level of insulin secretion becomes insufficient to maintain glucose homeostasis. Multiple factors may contribute to the onset of beta-cell failure, including genetics, autoimmune disorders, and chronic insulin resistance.4 The onset of GDM occurs as a result of the combined effects of glucose intolerance, hyperglycemia, and beta-cell dysfunction.3,4

Screening and Diagnosis

Diabetes Diagnosed During Pregnancy: GDM

Screening guidelines—pregnancy and postpartum: According to 2011 guidelines published by both AACE and the American Diabetes Association (ADA), GDM screening should be performed in all pregnant women at 24 to 28 weeks gestation.2,5

In addition, the ADA recommends diabetes screening in all at-risk patients as early in the pregnancy as possible, ideally at the first prenatal appointment. Individuals who are overweight (body mass index [BMI] ≥25 kg/m2) and satisfy any of the additional criteria shown in the table below are candidates for early prenatal diabetes screening.2,6

Table 1. Criteria for Early Prenatal Diabetes Testing

Diabetes Risk Factors2,5,6

Inactive/sedentary lifestyle

First-degree relative (parent or sibling) with diabetes

High-risk race/ethnicity (eg, African American, Latino, Native American, Asian American, Pacific Islander)

History of GDM or previous delivery of a large baby (>9 lbs)

High maternal birth weight (>9 lbs)

Hypertension (eg, blood pressure ≥140/90 mmHg)

HDL cholesterol level

History of polycystic ovary syndrome (PCOS)

A1C ≥5.7%, impaired fasting glucose (IFG), or impaired glucose tolerance (IGT) on a previous diabetes screening test

Other clinical conditions associated with insulin resistance (eg, severe obesity, acanthosis nigricans)

History of cardiovascular disease

Because some cases of GDM represent preexisting, undiagnosed T2DM, ADA guidelines specify that women with GDM should be screened for persistent diabetes for 6 to 12 weeks postpartum (using nonpregnant oral glucose tolerance test [OGTT] criteria).2

The ADA also recommends ongoing diabetes screening of women with a history of GDM, with testing conducted at least every 3 years to detect prediabetes or T2DM.2

GDM diagnosis: GDM is diagnosed by measuring a patient’s glucose levels using 1 of the following 2 approaches:

  • Administration of a 1-step 75-g 2-hour OGTT. This is the approach recommended by AACE.2,5
  • A 2-step process consisting of administration of a 50-g 1-hour glucose challenge test (GCT), followed by a 100-g 3-hour OGTT (if necessary).7

Whereas the OGTT requires an overnight fasting period of 8 to 12 hours, GCT screening can be conducted at any time of day, without constraints on patient food intake.8

However, the convenience of the initial GCT screening is offset by the need for a second 3-hour OGTT. Recently, the International Association of Diabetes in Pregnancy Study Groups (IADPSG) was formed and provided new guidelines for universal diagnostic criteria for identifying and treating GDM. This group recommended eliminating the 50-g GCT and endorsed the 75-g OGTT.9 This recommendation is based on the potential benefits of earlier diagnosis and treatment of hyperglycemia in pregnancy with 1-step screening compared with 2-step screening.

Universal testing will increase the prevalence of pregnant women with the diagnosis of diabetes from 9% to 18%. Proponents of this diagnostic approach including (AACE and the ADA) suggest it will enable earlier and more accurate identification of diabetes in pregnancy, thereby reducing the risk of poor outcomes for mothers and infants.2,5

Using the 1-step 75-g 2-hour OGTT, a GDM diagnosis is confirmed if results satisfy any of the criteria shown in the table below.

Table 2. GDM Diagnosis Using a 75-g 2-hour OGTT

GDM Diagnostic Criteria for 75-g 2-hour OGTT†2

Fasting plasma glucose (FPG)

≥92 mg/dL (5.1 mmol/L)

1-hour post-challenge glucose

≥180 mg/dL (10.0 mmol/L)

2-hour post-challenge glucose

≥153 mg/dL (8.5 mmol/L)

† A positive diagnosis requires that test results satisfy any 1 of these criteria.

If the fasting glucose is ≥92 mg/dL, there is no need to perform the OGTT88.

The American College of Obstetricians and Gynecologists (ACOG) recommends the 2-step diagnostic strategy because of the possibility that the 1-step approach will incur significant costs without producing clinically significant improvements in maternal or neonatal health outcomes.7 Traditionally, in the 2-step approach, a GCT 1-hour post-challenge glucose value >140 mg/dL is considered abnormal. However, the sensitivity of the 50-g GCT is improved if performed in a fasting state or a lower serum glucose threshold is used (130 mg/dL). In any case, follow-up with a 100-g 3-hour OGTT is required.8 GDM is diagnosed if ≥2 of the thresholds shown in the table below are exceeded.

Table 3. GDM Diagnostic Criteria for 100-g 3-hour OGTT Test†2

Status

Plasma or Serum Glucose Level
Carpenter and Coustan Conversion

Plasma Level
National Diabetes Data Group Conversion

Fasting

95 mg/dL (5.3 mmol/L)

105 mg/dL (5.8 mmol/L)

1 hour

180 mg/dL (10.0 mmol/L)

190 mg/dL (10.6 mmol/L)

2 hours

155 mg/dL (8.6 mmol/L)

165 mg/dL (9.2 mmol/L)

3 hours

140 mg/dL (7.8 mmol/L)

145 mg/dL (8.0 mmol/L)

† A positive diagnosis requires that ≥2 thresholds are met or exceeded.

Pregnancy in Established Diabetes

Women with established diabetes who want to become pregnant: All women of childbearing age who have been diagnosed with T1DM or T2DM and are considering becoming pregnant should receive preconception diabetes counseling.2

While ideal preconception blood glucose levels have not been established, women with diabetes who are planning to conceive should aim to achieve blood glucose levels and an A1C as close to normal as possible, while avoiding hypoglycemia, prior to becoming pregnant.2

  • AACE guidelines recommend a preconception target A1C value of <6.1%.5
  • Other experts recommend a preconception target A1C value of ≤6.0%, with self-monitored blood glucose levels at goal to minimize the risk of diabetes-related complications.10
  • Evidence indicates that every percentage point reduction in A1C levels established prior to conception is associated with a 50% decrease in the risk of an adverse pregnancy outcome.11,12

Normalizing blood glucose concentrations during the preconception period and early pregnancy can reduce the risks of spontaneous abortion and congenital malformations to levels comparable to that of the general population. Target blood glucose levels are <90 mg/dL prior to meals and <120 mg/dL 1 hour after the beginning of a meal.

In addition, women with preexisting diabetes should have a comprehensive preconception evaluation to diagnose and begin treatment for any diabetes-related complications such as retinopathy, nephropathy, neuropathy, or cardiovascular disease (CVD).2

Many of the medications used to treat diabetes and its complications (eg, statins, angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor blockers, and most non-insulin antihyperglycemic agents) are contraindicated or not recommended during pregnancy. As such, healthcare providers should educate patients before conception about the potential risks associated with continued use of these drugs and adjust their regimen accordingly.2,13

Potential contraindications to pregnancy include ischemic heart disease, untreated active proliferative retinopathy, renal insufficiency, and severe gastroenteropathy.8

Women with established diabetes who are not currently interested in conception: ADA guidelines recommend that all women of child-bearing potential who have been diagnosed with diabetes should be educated, starting at the onset of puberty, about the risks of pregnancy complications in individuals with uncontrolled diabetes.2 To minimize the risk of unintended pregnancy, women should be advised about the importance of effective contraception.2

Once a clear diagnosis of diabetes has been established, management is crucial. The next section will provide detailed information on the management of diabetes in pregnancy.

References

  1. American Diabetes Association. Gestational diabetes mellitus. Diabetes Care. 2004;27(Suppl 1):S88-S90.
  2. American Diabetes Association. Standards of medical care in diabetes–2013. Diabetes Care. 2013;36(Suppl 1):S11-S66.
  3. Inturrisi M, Lintner NC, Sorem KA. Diagnosis and treatment of hyperglycemia in pregnancy. Endocrinol Metab Clin North Am. 2011;40:703-726.
  4. Metzger BE, Buchanan TA, Coustan DR, et al. Summary and recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care. 2007;30(Suppl 2):S251-S260.
  5. Handelsman Y, Mechanick JI, Blonde L, et al. American Association of Clinical Endocrinologists. Medical guidelines for clinical practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2011;17(Suppl 2):1-53.
  6. Innes KE, Byers TE, Marshall JA, et al. Association of a woman's own birth weight with subsequent risk for gestational diabetes. JAMA. 2002;287:2534-2541.
  7. The American College of Obstetricians and Gynecologists. Committee opinion no. 504: Screening and diagnosis of gestational diabetes mellitus. Obstet Gynecol. 2011;118:751-753.
  8. Jovanovic L, Savas H, Mehta M, Trujillo A, Pettitt DJ. Frequent monitoring of A1C during pregnancy as a treatment tool to guide therapy. Diabetes Care. 2011;34:53-54.
  9. 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;33:676-682.
  10. Castorino K, Jovanovic L. Pregnancy and diabetes management: advances and controversies. Clin Chem. 2011;57:221-230.
  11. Mathiesen ER, Ringholm L, Damm P. Pregnancy management of women with pregestational diabetes. Endocrinol Metab Clin North Am. 2011;40:727-738.
  12. Inkster ME, Fahey TP, Donnan PT, et al. Poor glycated haemoglobin control and adverse pregnancy outcomes in type 1 and type 2 diabetes mellitus: systematic review of observational studies. BMC Pregnancy Childbirth. 2006;6:30.
  13. Kitzmiller JL, Block JM, Brown FM, et al. Managing preexisting diabetes for pregnancy: summary of evidence and consensus recommendations for care. Diabetes Care. 2008;31:1060-1079.