I. Problem/Condition.

The most common medical complication in pregnancy is diabetes mellitus. Diabetes in pregnancy increases the risk of several maternal and fetal complications and even mild maternal hyperglycemia is associated with adverse pregnancy outcomes.

Maternal risks

  • Gestational hypertension

  • Preterm labor

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  • Cesarean delivery

  • Postpartum infections

  • Subsequent Type 2 Diabetes Mellitus

Fetal risks

  • Macrosomia

  • Hyperbilirubinemia

  • Hypoglycemia

  • Shoulder dystocia

  • Brachial plexus injury

  • Respiratory Distress Syndrome

  • Congenital abnormalities

  • Intrauterine growth retardation

  • Spontaneous abortion and intrauterine death

  • Polyhydramnios

  • Polycythemia

  • Hypocalcemia

Post-natal complications

  • Childhood obesity

  • Metabolic syndrome

  • Diabetes mellitus type 2

Pathophysiology

  • The fetus is dependent on maternal glucose for energy

  • Glucose is transported from mother to fetus via facilitated diffusion across the placenta. Maternal and fetal insulin do not cross the placenta.

  • There is a physiologic increase in maternal insulin resistance during 24 to 30 weeks of gestation due to placental hormones which results in increased glucose transport away from the mother and to the growing fetus.

  • Abnormally high maternal glucose levels in the setting of gestational diabetes mellitus (GDM) translate to fetal hyperglycemia and hyperinsulinemia which, in turn, lead to fetal macrosomia and birth complications.

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

Gestational diabetes

Gestational diabetes is defined as any degree of glucose intolerance with onset or first recognition during pregnancy, whether or not the condition persisted, or possibly antedated or begun concomitantly with the pregnancy. The hyperglycemia and adverse pregnancy outcomes (HAPO) study showed that mild maternal hyperglycemia demonstrated strong association with increased birth weight and increased cord blood serum C-peptide.

Pre-gestational diabetes

The two broad classifications of diabetes is type 1 or type 2. Other types of diabetes may be due to monogenetic defects (mature-onset diabetes in the young), diseases of the exocrine pancreas (such as cystic fibrosis), medication, or chemically induced.

  • Type 1 diabetes mellitus is due to absolute deficiency of insulin from beta-cell destruction. The onset can be at any age, including in childhood. Because it is relatively less common compared to GDM or Type 2 Diabetes, it rarely presents initially in pregnancy. Insulin is the cornerstone of treatment.

  • Type 2 diabetes mellitus is due to progressive insulin secretory deficiency and insulin resistance. Typically seen in older patients, but has increased incidence among adolescents due to the high rate of obesity in the United States. It can be controlled by diet, exercise, oral hypoglycemic agents and insulin.

Pre-diabetes

These patients have elevated fasting glucose or hemoglobin A1c that are still below the diagnostic cut-off values for diabetes. They have increased risk for overt diabetes and cardiovascular disease. The Diabetes Prevention Program (DPP) showed that lifestyle intervention and pharmacological therapy (metformin) decreased the incidence of type 2 diabetes by 58% and 31% respectively.

B. Describe a diagnostic approach/method to the patient with this problem

The epidemic of obesity and type 2 diabetes mellitus in the United States has led to increased diagnosis of diabetes in pregnancy. Pre-natal care includes a complete medical evaluation, physical examination and diagnostic screening tests, fetal testing, surveillance, and rigorous follow-up. Women of child-bearing status with known diabetes should have pre-conception counseling and ideally achieve glycemic control prior to conception. Peri-natal glycemic control should be optimized with pharmacologic therapy. Nutrition education is essential to the management of diabetes. Daily physical activity and exercise should be advised. Multidisciplinary patient centered approach is recommended.

1. Historical information important in the diagnosis of this problem.

  • Do you have diabetes or pre-diabetes?

  • Do you have risk factors for diabetes?

    1st degree relative with diabetes

    Non-white risk ethnicity

    High blood pressure, heart disease, or high cholesterol

    Polycystic Ovarian Syndrome

    Overweight/obesity (BMI 25+ or 23+ if Asian)

    Previous GDM, pregnancy complication, or delivery of infant weighing more than 4500 g

  • Do you have symptoms of increased frequency in urination? Increased thirst? Increased appetite and excessive hunger?

  • If you have diabetes, do you have any complications from it? Retinopathy in particular can worsen during pregnancy and should be assessed with a retinal exam prior to pregnancy.

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

A complete physical examination is important with emphasis on the following:

  • Maternal blood pressure and weight

  • Ophthalmoscopic exam

  • Cardiopulmonary exam

  • Foot exam (including monofilament sensory testing)

  • Peripheral pulses check

  • Skin exam

  • Fetal assessment

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing this problem.

  • Hemoglobin A1C

  • Oral glucose tolerance test

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

Gestational diabetes

At the first prenatal visit, testing for undiagnosed diabetes should be performed using standard methods. For those without pre-existing diabetes, GDM screening can be done at 24-28 weeks of gestation using 2 different methods. The “one-step” approach appeared in revised screening guidelines for gestational diabetes in 2011 (American Diabetes Association and International Association of Diabetes and Pregnancy Study Groups). The “two-step” approach was endorsed by an NIH consensus committee in 2013.

One-step approach:

  • Perform 75 g oral glucose tolerance test (OGTT) with fasting glucose and at 1 and 2 hours. OGTT must be done fasting for an overnight fast of 8 hours in the morning. Diagnosis of GDM is made with the following plasma glucose values:

    Fasting ≥ 92 mg/dL

    1 hour ≥ 180 mg/dL

    2 hours ≥ 153 mg/dL

Two-step approach:

  • Perform a 50 g OGTT (non-fasting) with plasma glucose measurement at 1 hour. If the level is >135 or 140 mg/dL, proceed with step 2.

  • Perform a 100 g OGTT with the following four plasma glucose measurements. Diagnosis of GDM is made with the following plasma glucose values:

    Fasting ≥ 95 mg/dL

    1 hour ≥180 mg/dL

    2 hours ≥155 mg/dL

    3 hours ≥ 140 mg/dL

  • Screen GDM women for persistent diabetes 6-12 weeks postpartum.

  • Screen women with GDM history at least every 3 years.

Pre-gestational diabetes:

The 2017 American Diabetes Association diagnostic criteria for diabetes mellitus can be any of the following:

  • Hemoglobin A1C ≥ 6.5% test should be performed using methods that are certified by the National Glycohemoglobin Standardization Program and standardized to the Diabetes Control and Complications Trial.

  • Fasting plasma glucose ≥ 126 mg/dL. Fasting should involve no caloric intake for at least 8 hours.

  • 2-hour plasma glucose ≥ 200 mg/dL during OGTT using 75g of glucose load.

  • Random plasma glucose ≥ 200 with classic symptoms.

Pre-diabetes:

Patients with A1C between 5.7-6.4%, impaired fasting glucose (100-125 mg/dL) or impaired glucose tolerance (2 hour OGTT values 140-199 mg/dL) have pre-diabetes. They have increased risk for overt diabetes and cardiovascular disease. Any woman with pre-diabetes diagnosed during or before pregnancy should be managed as someone with pre-gestational diabetes.

The Diabetes Prevention Program (DPP) showed that lifestyle intervention and pharmacological therapy (metformin) decreased the incidence of type 2 diabetes by 58% and 31% respectively.

III. Management while the Diagnostic Process is Proceeding

A. Management of Diabetes in Pregnancy:

Pre-conception care

  • A complete medical evaluation and physical exam is recommended on the initial visit.

  • A1C should be less than 6.5% before conception is attempted.

  • At puberty, pre-conception counseling should be started during diabetes clinic visits.

  • Diabetic retinopathy, neuropathy and nephropathy screening for those who are planning pregnancy.

  • Medication review is needed because most commonly used drugs may be contraindicated in pregnancy, including statins, ACE-inhibitors, angiotensin II receptor blockers, and oral hypoglycemic agents.

  • Multidisciplinary patient centered approach is recommended.

Perinatal glycemic control:

  • Fingerstick glucose targets are generally lower in pregnancy: fasting/pre-meal: ≤95 mg/dL, 1 hour post-prandial ≤140 mg/dL or 2 hour post-prandial ≤ 120 mg/dL

  • Hemoglobin A1c generally not exceeding 6.0-6.5%

  • Nutrition education to support balanced diet for a healthy pregnancy

  • Daily physical activity and exercise

  • Depression screening

  • Insulin therapy if glucose targets are not met with diet and exercise alone

  • Short-term studies support the use of metformin or sulfonylureas but both cross the placenta and long-term studies are lacking.

  • Other non-insulin agents are not well studied in pregnancy and should generally be avoided.

Intrapartum management:

  • Goal of care during labor is to avoid maternal hyperglycemia and neonatal acidemia and hypoglycemia.

  • Target glucose control is between 70-110 mg/dL per the American College of Obstetricians and Gynecologists’ recommendations.

  • Overt hypoglycemia (<50 mg/dL) or hyperglycemia (>180 mg/dL) should be prevented.

  • Due to increased caloric requirement during prolonged labor or active labor, intravenous 5% dextrose solution is given, usually with insulin infusion. Intravenous insulin and glucose infusions are usually used for women who required insulin prior to pregnancy (e.g., type 1 diabetes), while those with controlled gestational diabetes rarely require insulin during labor.

  • Protocols for insulin therapy and intravenous fluids appear in Protocols section.

  • Glucose monitoring done at 1-2 hours during active labor; every 2-4 hours during early labor.

  • For scheduled Cesarean delivery, the night time basal insulin or oral agent should be given, but oral agents and short acting insulins should be held on the day of the procedure.

Inpatient diabetic emergencies

  • Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the most serious and immediate threats to the life of the mother and fetus. Immediate fluid resuscitation, insulin therapy and correction of electrolyte abnormalities are the most important treatments and the approach is the same as in the non-pregnant state.

  • Maternal hypoglycemia should be recognized early to give prompt attention with either oral or intravenous glucose, or intramuscular glucagon.

Postpartum management

  • Insulin resistance decreases immediately after delivery of the fetus and the placenta, hence blood glucose monitoring immediately postpartum is important.

  • In the setting of GDM, glucose levels will normalize after delivery and postpartum insulin is not needed.

  • In the setting of type 1 diabetes, the patient’s insulin regimen should be resumed with the first dose of basal insulin properly overlapping with the cessation of the insulin infusion. Mealtime and correctional insulin should also be restarted as needed. Insulin resistance has decreased dramatically after delivery and thus one should anticipate that insulin requirements will drop significantly from those of third-trimester.

  • In the setting of type 2 diabetes, insulin requirements in the hospital dosing will vary depending on extent of disease.

  • Patients with gestational diabetes should continue diet and exercise and should undergo OGTT screening 6-12 weeks postpartum and every 3 years.

  • For women with type 1 diabetes, blood glucose monitoring advised during breastfeeding due to high metabolic demands.

Protocols for intrapartum management of diabetes
American College of Obstetrics and Gynecology Guideline 2005

  • Usual dose of intermediate-acting insulin is given at bedtime.

  • Morning dose of insulin is held.

  • Intravenous saline solution started.

  • Once active labor begins or glucose levels decrease to less than 70 mg/dL, change fluids to 5% dextrose and delivered at a rate of 100–150 cc/h (2.5 mg/kg/min) to achieve a target glucose level of 100 mg/dL.

  • Check glucose levels hourly.

  • Regular insulin is administered by intravenous infusion at a rate of 1.25 U/h if glucose levels exceed 100 mg/dL.

  • Titrate insulin or glucose infusion according to glucose readings.

Rotating fluids protocol for gestational diabetes and type 2 diabetes

  • Use dextrose 5% normal saline at rate of 125 mL/hour for maternal glucose level <100 mg/dL.

  • Use lactated Ringer’s solution at rate of 125 mL/hour for maternal glucose level between 101-140 mg/dL.

  • Use regular or short acting insulin infusion and lactated Ringer’s at 125 mg/hour for maternal glucose >140 mg/dL.

  • Titrate insulin infusion to achieve target glucose level of 100 mg/dL.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem

  • Uncontrolled diabetes in pregnancy poses serious risks to maternal and fetal well-being.

  • Goal of care during labor is to avoid maternal hyperglycemia, neonatal acidemia and hypoglycemia.

  • Intrapartum management of diabetes includes intensive glucose monitoring, intravenous fluids and insulin infusion to target glucose level goal of 70-110 mg/dL.

  • Maternal hypoglycemia and diabetic ketoacidosis are medical emergencies that need prompt recognition and attention.

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