What is gestational diabetes mellitus (GDM) and how is it managed?

Gestational Diabetes Mellitus: Comprehensive Overview

Definition and Epidemiology

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy, regardless of whether insulin or diet modification is used for treatment, and whether or not the condition persists after pregnancy. 1 This definition encompasses the possibility that unrecognized glucose intolerance may have existed before or begun simultaneously with pregnancy 1.

• GDM complicates approximately 7% of all pregnancies in the United States, resulting in more than 200,000 cases annually 1
• The prevalence ranges from 1-14% depending on the population studied and diagnostic criteria employed 1
• The prevalence has increased by 35-100% in recent years 2

Pathophysiology and Risk Factors

During normal pregnancy, insulin sensitivity progressively declines with advancing gestation due to placental factors, progesterone, and estrogen 3. In physiological pregnancy, pancreatic β-cells compensate by increasing insulin secretion to maintain normal glucose homeostasis 3. GDM occurs when pancreatic β-cells cannot meet the increased insulin demand during pregnancy 3.

High-Risk Characteristics Requiring Early Screening

Women meeting any of the following criteria should undergo glucose testing as soon as feasible after pregnancy confirmation 1:

• Severe obesity (marked obesity) 1
• Prior history of GDM or delivery of large-for-gestational-age infant 1
• Presence of glycosuria 1
• Strong family history of type 2 diabetes (first- or second-degree relatives) 1
• Diagnosis of polycystic ovary syndrome (PCOS) 1
• Age >35 years 4
• History of malformation, stillbirth, successive abortions, or previous birth weight >4500g 4, 5
• Ethnic origin with increased risk (Arab, South and Southeast Asian, Latin American, Native American, African American, Pacific Islander) 1, 4

Low-Risk Status (No Screening Required)

Women meeting ALL of the following characteristics do not require GDM screening 1:

• Age <25 years
• Normal weight before pregnancy
• Member of ethnic group with low diabetes prevalence
• No known diabetes in first-degree relatives
• No history of abnormal glucose tolerance
• No history of poor obstetrical outcomes

Screening and Diagnosis

Timing of Screening

• High-risk women: Screen immediately upon pregnancy confirmation; if normal, retest at 24-28 weeks 1
• Average-risk women: Screen at 24-28 weeks of gestation 1
• Low-risk women: No screening required 1

Diagnostic Approaches

Two validated approaches exist for GDM screening at 24-28 weeks 1:

Two-Step Approach (Most Common)

1. Initial screening: 50g oral glucose challenge test (GCT) 1

   • Threshold of 140 mg/dL identifies 80% of women with GDM 1
   • Threshold of 130 mg/dL increases sensitivity to 90% 1

2. Diagnostic confirmation: 100g oral glucose tolerance test (OGTT) performed on a separate day for women exceeding the threshold 1

One-Step Approach

• Perform diagnostic 75g OGTT directly in all women at 24-28 weeks 1
• May be cost-effective in high-risk populations 1

Diagnostic Criteria (100g OGTT)

GDM is diagnosed when at least TWO of the following plasma glucose values are met or exceeded 1:

• 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)

Alternative Diagnostic Criteria (75g OGTT - International Consensus)

GDM is diagnosed when ONE or more of the following values are met 4:

• 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)

Early Pregnancy Screening for Overt Diabetes

High-risk women should be screened at first prenatal visit using standard diagnostic criteria 1, 4:

• Fasting plasma glucose ≥126 mg/dL indicates overt diabetes 4
• Random glucose ≥200 mg/dL indicates overt diabetes 4
• HbA1c ≥6.5% before 20 weeks of gestation indicates overt diabetes 4

Management Strategy

First-Line Treatment: Lifestyle Modifications

Lifestyle behavior change is the cornerstone of GDM management and suffices as treatment for 70-85% of women diagnosed under traditional criteria 1, 6. This proportion is expected to increase with lower diagnostic thresholds 1.

Medical Nutrition Therapy

Medical nutrition therapy should be developed with a registered dietitian familiar with GDM management 1, 6. Specific dietary requirements include 1, 6:

• Minimum 175g of carbohydrate daily 1, 6
• Minimum 71g of protein daily 6
• 28g of fiber daily 6
• Emphasis on monounsaturated and polyunsaturated fats while limiting saturated fats and avoiding trans fats 6
• Adequate calorie intake to promote fetal/neonatal and maternal health while achieving glycemic targets 1

Physical Activity

Women should be motivated to increase physical activity to moderate intensity levels if not contraindicated 4, 5.

Glycemic Targets

The recommended glycemic targets for GDM management are 1, 6, 7:

• Fasting glucose <95 mg/dL (5.3 mmol/L) 1, 6
• 1-hour postprandial glucose <140 mg/dL (7.8 mmol/L) 1, 6
• 2-hour postprandial glucose <120 mg/dL (6.7 mmol/L) 1, 6

For women on insulin, additional lower limits apply to prevent hypoglycemia 1.

Self-Monitoring of Blood Glucose

Self-monitoring of blood glucose is essential to assess glycemic control and guide treatment decisions 6, 4.

Second-Line Treatment: Pharmacological Therapy

When to Initiate Medication

Insulin should be added if glycemic targets cannot be achieved with lifestyle modifications alone within 1-2 weeks 1, 7.

Insulin: First-Line Pharmacological Agent

Insulin is the preferred medication for treating hyperglycemia in GDM because it does not cross the placenta to a measurable extent 1, 6, 7. Key prescribing principles include 1, 7:

• Smaller proportion as basal insulin, greater proportion as prandial insulin 1, 7
• Frequent titration required due to rapidly changing insulin resistance, particularly in the second trimester 1
• Weekly or biweekly dose increases typically needed in the second trimester 1
• Most insulins are pregnancy category B, except glargine and glulisine (category C) 1

Oral Agents: Not Recommended as First-Line

Metformin and glyburide should NOT be used as first-line agents because both cross the placenta to the fetus 1, 6, 7. Additional concerns include:

• Glyburide has been associated with increased neonatal hypoglycemia and macrosomia compared to insulin 6
• Other oral and non-insulin injectable glucose-lowering medications lack long-term safety data 1
• Metformin used for PCOS and ovulation induction should be discontinued by the end of the first trimester 1

Specialized Care

Due to the complexity of insulin management in pregnancy, referral to a specialized center is recommended if available 1.

Telehealth Option

Telehealth visits for GDM patients improve outcomes compared with standard in-person care, including reductions in cesarean delivery, neonatal hypoglycemia, premature rupture of membranes, macrosomia, pregnancy-induced hypertension/preeclampsia, preterm birth, neonatal asphyxia, and polyhydramnios 1, 7.

Monitoring During Pregnancy

Maternal Monitoring

• Blood pressure and urinary protein should be monitored at each prenatal visit due to increased risk of hypertensive disorders 6
• Regular obstetric examinations including ultrasound are recommended 4
• For women requiring medications or with poor glucose control, fetal surveillance is suggested starting at 32 weeks of gestation 8

Continuous Glucose Monitoring (CGM)

CGM has demonstrated value in pregnancy complicated by type 1 diabetes, showing mild A1C improvement without increased hypoglycemia and reductions in large-for-gestational-age births 1. However, there are insufficient data to support routine CGM use in women with type 2 diabetes or GDM 1.

For type 1 diabetes in pregnancy, CGM target ranges are 1:

• Time in range (63-140 mg/dL): goal >70%
• Time below range (<63 mg/dL): goal <4%
• Time below range (<54 mg/dL): goal <1%
• Time above range (>140 mg/dL): goal <25%

HbA1c Monitoring

HbA1c should be used as a secondary measure, not primary, due to increased red blood cell turnover during pregnancy 1. The recommended A1C target in pregnancy is <6% if achievable without hypoglycemia 1. Given altered red blood cell kinetics, A1C may need monthly monitoring 1.

Maternal and Fetal Complications

Short-Term Risks

GDM is characterized by increased risk of 1:

• Large-for-gestational-age birth weight and macrosomia 1, 8
• Neonatal hypoglycemia 1, 8
• Neonatal respiratory distress 8
• Shoulder dystocia 8
• Operative delivery 8
• Hypertensive disorders of pregnancy 8

These risks increase progressively with maternal hyperglycemia, with no clear inflection points 1, 6. The mechanism involves fetal hyperinsulinism in response to maternal hyperglycemia, leading to macrosomia 3.

Long-Term Maternal Risks

Women with GDM are at substantially increased risk for developing type 2 diabetes after pregnancy 1. Specific considerations include:

• 50-70% risk of developing type 2 diabetes over 15-25 years 7
• Obesity and insulin resistance enhance the risk of type 2 diabetes 1
• Markers of islet cell-directed autoimmunity are associated with increased risk of type 1 diabetes 1
• Interpregnancy or postpartum weight gain increases risk of adverse outcomes in subsequent pregnancies and earlier progression to type 2 diabetes 1

Long-Term Offspring Risks

Offspring of women with GDM are at increased risk of 1:

• Obesity in late adolescence and young adulthood 1
• Glucose intolerance and diabetes in childhood 1
• Reduced insulin sensitivity and impaired β-cell compensation 1

Postpartum Management

Immediate Postpartum Period

Insulin resistance typically resolves after delivery 8. Neonatal care of GDM offspring at high risk for hypoglycemia includes blood glucose measurements after birth and appropriate intervention if necessary 4.

Postpartum Screening

Because GDM may represent preexisting undiagnosed type 2 diabetes, women with GDM should be screened for persistent diabetes or prediabetes at 6-12 weeks postpartum using nonpregnancy criteria 1, 4. The recommended test is a 75g OGTT using WHO criteria 4, 5.

Long-Term Follow-Up

Women with normal glucose tolerance postpartum should undergo screening every 1-3 years thereafter depending on other risk factors 1. Assessment should include fasting glucose, random glucose, HbA1c, or optimally OGTT 4.

Prevention of Type 2 Diabetes

Both metformin and intensive lifestyle intervention prevent or delay progression to diabetes in women with a history of GDM 1. Specific recommendations include:

• Continued lifestyle modifications including weight management and physical activity 1, 4, 8
• Breastfeeding provides longer-term metabolic benefit to both mother and offspring 1, 8
• In the Nurses' Health Study II, subsequent diabetes risk was significantly lower in women who followed healthy eating patterns 1
• Only 5-6 individuals with GDM history and impaired glucose tolerance need treatment to prevent one case of diabetes 1

Contraception

All women of childbearing age, including those postpartum, should have contraception options reviewed at regular intervals 1.

Common Pitfalls and Caveats

Premature Medication Escalation

A critical pitfall is failing to recognize that 70-85% of women can manage GDM with lifestyle modification alone, potentially leading to unnecessary medication use 6, 7. Adequate time (1-2 weeks) should be allowed for lifestyle modifications to take effect before declaring treatment failure 7.

Inadequate Lifestyle Intervention

Before initiating pharmacological therapy, verify that adequate lifestyle modifications have been implemented, including consultation with a registered dietitian, meeting minimum dietary requirements, and appropriate physical activity 7.

Using Oral Agents as First-Line Therapy

Assuming oral antihyperglycemic agents are equivalent to insulin in safety and efficacy is a significant error 6. Insulin remains the gold standard due to its inability to cross the placenta and superior safety profile 1, 6, 7.

Inadequate Monitoring Frequency

Insulin requirements change dramatically throughout pregnancy, requiring frequent dose adjustments 7. In the first trimester, total daily insulin dose often decreases, while in the second trimester, rapidly increasing insulin resistance necessitates weekly or biweekly increases 1.

Forgetting Postpartum Follow-Up

Women with GDM history have 50-70% risk of developing type 2 diabetes over 15-25 years, making postpartum screening and long-term follow-up crucial 7. All women must be instructed about their increased risk and possible preventive measures 4.

Inappropriate Use of Bariatric Surgery Patients

After bariatric surgery, OGTT is not recommended due to risk of postprandial hypoglycemia 4. Alternative screening methods should be employed in this population.