Hospital Medicine

Diabetes Mellitus and Pregnancy

I. Problem/Condition.

The most common medical complication in pregnancy is diabetes mellitus. Poorly controlled diabetes in pregnancy poses maternal and fetal risks and complications. Furthermore, recent studies have shown that mild maternal hyperglycemia are associated with adverse pregnancy outcomes.

Maternal risks

  • Gestational hypertension

  • Cardiovascular disease

  • Metabolic syndrome

  • Preterm labor

  • Cesarean delivery

  • Postpartum infections

  • Diabetes mellitus type 2

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 through the placenta, however maternal or fetal insulin are not

  • High maternal glucose levels translate to fetal hyperglycemia and hyperinsulinemia

  • Fetal hyperinsulinemia leads to macrosomia and fetal complications

  • There is increased maternal insulin resistance during 24 to 30 weeks of gestation due to placental steroids and hormones

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.

Pregestational diabetes

The two broad classifications of diabetes is type 1 or type 2. In some patients, classification may not be well defined at clinical presentation and as the disease progresses, it becomes much clearer. 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 is usually in the young and rarely present during 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 for severely uncontrolled diabetes.

Pre-diabetes

These patients 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 lead 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. Patients with known type 1 diabetes should have pre-conception counseling at puberty. Peri-natal gylcemic 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? Do you have a family history of diabetes?

  • Do you have high blood pressure? Heart disease?

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

  • On your previous pregnancies, were you ever told that you have gestational diabetes? Or border-line high blood sugar?

  • On your previous pregnancies, have you had a fetus weigh 4500g or more (i.e. "large baby" )? Fetal abnormalities? Fetal distress? Fetal complications? Adverse fetal outcomes?

  • If you have diabetes, do you have type 1 or type 2? And what medications are you taking to control it? Oral medicines? Insulins? Injectables?

  • If you have diabetes, do you have any complications from it? Kidney disease? Blindness? Nerve problems? Any organ damage?

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 the cause of this problem.

  • Hemoglobin A1C

  • Fasting plasma glucose

  • Random plasma glucose

  • Oral glucose tolerance test

  • Glucose fingerstick monitoring

  • Urinalysis and microalbumin

  • Fetal surveillance (ultrasonography, non-stress testing, and amniotic fluid indices)

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

Gestational diabetes

New revised screening guidelines for gestational diabetes 2011 (American Diabetes Association and International Association of Diabetes and Pregnancy Study Groups):

  1. Screen for undiagnosed diabetes on the first prenatal visit using standard guidelines.

  2. Perform 75g oral glucose tolerance test (OGTT ) with fasting glucose and at 1 and 2 hours, at 24-28 weeks' age of gestation in women not previously diagnosed with overt diabetes mellitus. OGTT must be done fasting for at overnight fast of 8 hours in the morning. Diagnosis of gestational diabetes millitus (GDM) is made with the following plasma glucose values:

  • Fasting >= 92mg/dl

  • 1 hour >= 180mg/dl

  • 2 hours >= 153mg/dl

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

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

Pregestational diabetes

The 2010 American Diabetes Association diagnostic criteria for diabetes mellitus can be any of the following:

  • 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 >= 126mg/dl. Fasting should involve no caloric intake for at least 8 hours.

  • 2-hour plasma glucose >= 200mg/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 (100-125mg/dl) or impaired glucose tolerance (2 hour OGTT values 140-199mg/d) have pre-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.

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 7% 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 contraindicted in pregnancy, including statins, ACE-inhibitors, angiotensin II receptor blockers, and oral hypoglycemic agents.

  • Multidisciplinary patient centered approach is recommended.

Perinatal glycemic control

  • Optimal glycemia recommended is fasting, bedtime and pre-meal glucose of 60-99mg/dl and post-prandial glucose of 100-129mg/dl.

  • Prescribe nutrition education to support balanced diet for a healthy pregnancy.

  • Advise daily physical activity and exercise.

  • Screen for depression.

  • Start insulin therapy (subcutaneous NPH twice or thrice daily, or insulin pump). No evidence has been documented for increased adverse fetal outcomes with the use of insulin glargine in pregnancy compared to the use of NPH insulin. Glargine should be considered in uncontrolled diabetes, and in those patients taking this before conception.

  • Metformin may be used for gestational diabetes and pregnant women with polycystic ovarian disease.

  • Newer oral agents (thiazolidinediones, meglitinide analogs, alpha-glucosidase inhibitors and incretins) are not well studied in pregnancy.

Intrapartum management

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

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

  • Overt hypoglycemia (<50mg/dl) or hyperglycemia (>180mg/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 type 1 diabetic mothers, and 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 cornestone treatments. They are treated the same way as they are 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.

  • If the mother is eating after delivery, basal insulin should be restarted and oral hypoglycemic agents started 24-48 hours postpartum.

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

  • 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 70mg/dL, change fluids to 5% dextrose and delivered at a rate of 100–150cc/h (2.5mg/kg/min) to achieve a target glucose level of 100mg/dL.

  • Check glucose levels hourly.

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

  • Titrate insulinor glucose infusion according to glucose readings.

Rotating fluids protocol for gestational diabetes and type 2 diabetes

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

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

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

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

  • New criteria for diagnosing gestational diabetes uses lower glucose level than previous guidelines.

  • 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 70-110mg/dL.

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

IV. What's the evidence?

Reece, EA. "The fetal and maernal consequences of gestational diabetes mellitus". J Matern Fetal Neonatal Med. vol. 23. 2010. pp. 203.

Metzger, BE, Lowe, LP, Dyer, AR. "Hyperglycemia and adverse pregnancy outcomes". N Engl JMed. vol. 8;358. 2008. pp. 1991-2002.

Bevier, WC, Fischer, R, Jovanovic, L. "Treatment of women with an abnormal glucose challenge test (but a normal glucose olerance test) decreases the prevalance of macrosomia". Am JPerinatol. vol. 16. 1991. pp. 269-75.

Crowther, CA, Hiller, JE, Moss, JR. "Effect of treatment of gestational diabetes mellitus on pregnancy outcomes". N Engl J Med 16. vol. 352. 2005. pp. 2477-86.

"Standards of medical care in diabetes- 2011". Diabetes Care. vol. 34. 2011. pp. S11-61.

"The Diabetes Prevention Program: descripion of lifestyle intervention". Diabetes Care. vol. 25. 2002. pp. 2165-71.

Kjos, SL, Leung, A, Henry, OA. "Antepartum surveillane in diabetic pregnancies: predictors of fetal distress in labor". Am J Obstet Gynecol.. vol. 173. 1995. pp. 1532-9.

Metzger, BE, Buchanan, TA, Coustan, DR. "Summary and recommendations of the ffith internaional Workshop-conference on gestational diabetes diabetes mellitus". Diabetes Care. vol. 30. 2007. pp. S251-60.

Kitzmiller, JL, Block, JM, Catalano, PM. "Managing pre-existing diabetes for pregnancy: summary of evidence and consensus recommendations for care". Diabetes Care. vol. 31. 2008. pp. 1060-79.

Pollex, E, Moreti, ME, Koren, G. "Safety of insulin glargine use in pregnancy: a systematic review and meta-analysis". Ann Pharmacother. vol. 45. 2011. pp. 9-16.

Pantoline, KM, Faiman, C, Olansk, L. "Insulin glargine use during pregnancy". Endocr Pract. vol. 17. 2011. pp. 448-55.

Feig, DS, Moses, RG. "Metformin therapy during pregnancy: good for the goose and good for the gosling too?". Diabetes Care. vol. 34. 2011. pp. 2329-30.

"Clinical management guidelines for obstetrics-gynecologists. Pre-gestational diabetes mellitus". Obstet Gynecol. vol. 105. 2005. pp. 675-85.

Rosenberg, VA, Eglinton, GS, Rauch, ER. "Intrapartum maternal glycemic control in women with insulin requiring diabtes: a randomized clinical trial of rotating fluids versus insulin drip". Am J Obstet Gynecol.. vol. 195. 2006. pp. 1095-9.

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