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Gestational Diabetes Mellitus


Basics


Description


  • Gestational diabetes mellitus (GDM) is the new onset of diabetes mellitus (DM) or impaired glucose tolerance during pregnancy.
    • Maternity care providers should distinguish between preexisting but undiagnosed type 2 diabetes mellitus (T2DM) and GDM.
    • GDM that persists beyond pregnancy should be reclassified as T2DM.
  • A1 GDM refers to GDM controlled by lifestyle alone.
  • A2 GDM refers to pharmacologically managed GDM and implies suboptimal glycemic control.

Epidemiology


Prevalence
  • 6-7% of pregnancies in United States may be as high as 18% with more recently proposed diagnostic criteria (see "Diagnostic Tests"� below).
  • Highest among Hispanic, African American, Native American, Asian, and Pacific Islander women
  • Varies according to local prevalence of T2DM
  • Increasing globally

Etiology and Pathophysiology


  • The etiology of GDM is poorly understood.
  • During pregnancy, the placenta produces several hormones that can cause or exacerbate insulin resistance in susceptible individuals.

Genetics
  • Incompletely understood
  • Strong family association
  • Polygenic risk plus environmental factors

Risk Factors


  • History of GDM in previous gestation
  • History of impaired glucose metabolism (A1c ≥5.7%, impaired glucose tolerance, or impaired fasting glucose)
  • Obesity (body mass index [BMI] ≥30 kg/m2)
  • Overweight (BMI ≥25 kg/m2) with additional risk factors
    • Physical inactivity
    • Diabetes in 1st-degree relative
    • High-risk ethnicity (see "Prevalence"� above)
    • Previous delivery of baby weighing >9 lb
    • Hypertension
    • HDL cholesterol <35 mg/dL
    • Triglyceride level >250 mg/dL
    • Polycystic ovary syndrome

General Prevention


  • Weight loss or maintain healthy weight before pregnancy.
  • Regular exercise including both aerobic and resistance training (based on data from observational studies).

Commonly Associated Conditions


  • Prediabetes
    • Impaired fasting glucose
    • Impaired glucose tolerance
    • A1c 5.7-6.4%
  • Hypertensive disorders of pregnancy
    • Gestational hypertension
    • Preeclampsia

Diagnosis


History


  • Usually asymptomatic
  • Ask all pregnant women about risk factors (see above) at first prenatal visit.

Physical Exam


  • May be normal
  • Overweight, obesity common
  • Acanthosis nigricans suggests T2DM.
  • Excessive weight gain may occur during pregnancy complicated by GDM.
  • Excessive fundal height may indicate fetal macrosomia.

Differential Diagnosis


  • Preexisting/pregestational T2DM
  • Stress hyperglycemia

Diagnostic Tests & Interpretation


Initial Tests (lab, imaging)
  • Screen for undiagnosed T2DM at the first prenatal visit in women with risk factors (see above) using standard criteria (1)[A]:
    • A1c ≥6.5%
    • Fasting serum glucose ≥126 mg/dL
    • 2-hour postprandial glucose ≥200 mg/dL
  • Screen for GDM at 24-28 weeks of gestation in pregnant women not previously known to have diabetes. Both two-step and one-step methods of screening are acceptable (2).
  • Standard two-step screening for GDM endorsed by the American College of Obstetricians and Gynecologists (ACOG) (2,3)[A]:
    • Step 1: 1-hour nonfasting 50-g glucose load test (GLT); if 1-hour plasma glucose meets or exceeds threshold then proceed to step 2; threshold may be set at 140 mg/dL, 135 mg/dL, or 130 mg/dL (American Diabetes Association endorses 140 mg/dL).
    • Step 2: 3-hour fasting 100-g oral glucose tolerance test (OGTT); the diagnosis of GDM is made when ≥2 glucose values are met or exceeded using either of two accepted sets of criteria:
      • Carpenter/Coustan
        • Fasting ≥95 mg/dL
        • 1 hour ≥180 mg/dL
        • 2 hour ≥155 mg/dL
        • 3 hour ≥140 mg/dL
      • National Diabetes Data Group
        • Fasting ≥105 mg/dL
        • 1 hour ≥190 mg/dL
        • 2 hour ≥165 mg/dL
        • 3 hour ≥145 mg/dL
  • Alternative one-step screening for GDM (1)[A]
    • 2-hour fasting 75-g OGTT; the diagnosis of GDM is made when any of the following glucose values are met or exceeded:
      • Fasting ≥92 mg/dL
      • 1 hour ≥180 mg/dL
      • 2 hour ≥153 mg/dL
  • The use of lower thresholds for any test (1-hour GLT, 3-hour OGTT, or one-step vs. two-step screening) is more sensitive and will result in a greater number of women being diagnosed with GDM. However, at present, the clinical benefit of heightened sensitivity is uncertain.

Follow-up tests & special considerations
Screening for GDM may be considered optional for women at very low risk for GDM (i.e., non-Hispanic White, <25 years of age, BMI <25 kg/m2, no history of GDM or glucose intolerance, and no 1st-degree relative with diabetes); this is only 10% of the U.S. obstetric population. �
Diagnostic Procedures/Other
  • Ultrasound at 37-39 weeks of gestation for estimated fetal weight (evaluation for fetal macrosomia, see "Surger/Other Procedures"� below)
  • Antenatal testing, typically some combination of the following performed twice weekly beginning in 3rd trimester for A2 GDM, although current evidence does not support a particular protocol.
    • Fetal nonstress test (NST; reactive with ≥2 accelerations in 20-40 minutes)
    • Amniotic fluid index (AFI; normal >5 cm)
    • Biophysical profile (BPP; presence or absence of five variables; score of ≥8 out of 10 including AFI >5 cm is normal)
    • Modified BPP (NST plus AFI, equivalent to BPP if NST reactive and AFI >5 cm)

Treatment


General Measures


  • Treatment benefits both mother and fetus (1,2,4)[A].
  • Dietary therapy for all women with GDM
  • Add medication when necessary for glycemic control.
  • Oral medications not FDA-approved for GDM but equivalent to insulin in efficacy

Medication


First Line
  • Metformin 500-1,000 mg by mouth b.i.d. with meals (2,5)[A]
  • Glyburide 2.5-10 mg by mouth b.i.d. (2)[A]
    • Do not use in patients who have sulfa allergy.
  • Insulin 0.7-1 unit/kg/day in divided doses; usually given half as intermediate-acting (either NPH or detemir) and half as rapid-acting (either lispro or aspart) with meals (1,2)[A]:
    • Insulin NPH 0.35-0.5 units/kg/day SUBQ divided b.i.d. or t.i.d. or
    • Insulin detemir 0.35-0.5 units/kg/day SUBQ daily or divided b.i.d. plus
    • Insulin lispro or insulin aspart 0.35-0.5 units/kg/day SUBQ divided t.i.d. with meals

Second Line
Combination therapy (usually metformin + insulin) �

Issues for Referral


  • Nutrition counseling by registered dietician
  • Diabetic education if available
  • Consider perinatology consult for
    • Poor glycemic control
    • Maternal comorbidities
    • Other high risk or management uncertainty

Additional Therapies


Exercise probably beneficial and safe but not well studied in GDM. �

Surgery/Other Procedures


  • Consider scheduled cesarean section in GDM if estimated fetal weight ≥4,500 g (2)[C].
  • Evidence is insufficient to recommend delivery at any particular gestational age.
    • Women with GDM with good glycemic control by diet or medication and no other complications usually can be managed expectantly until ≥39 weeks of gestation (2)[C].
    • Some obstetricians recommend delivery between 39 and 40 weeks of gestation as with well-controlled, pregestational diabetes.
    • Others recommend induction at 39 weeks in A2 GDM and at 41 weeks in A1 GDM.

Inpatient Considerations


Admission Criteria/Initial Stabilization
  • Periodic glucose monitoring during labor
  • Intrapartum glycemic control (ideally 70-110 mg/dL) is important for minimizing risk of neonatal hypoglycemia.

IV Fluids
  • Normal saline (NS) or lactated Ringer (LR) with or without 5% dextrose (D5) depending on glucose levels, stage of labor, and need for insulin to maintain glycemic control during labor
  • ACOG protocol
    • NS at start of labor
    • D5NS at 100-150 mL/hour if glucose <70 mg/dL or during active labor
    • Regular insulin at 1.25 units/hour (10 units per 1,000 mL D5NS at 125 mL/hour) if glucose >100 mg/dL

Nursing
  • Resume normal diet and discontinue pharmacotherapy postpartum.
  • Monitor glucose for 24-72 hours postpartum to confirm normalization.
  • Breastfeeding helps with maternal glucose metabolism and should be encouraged.

Discharge Criteria
Euglycemic and otherwise stable �

Ongoing Care


Follow-up Recommendations


  • Routine postpartum follow-up unless pharmacotherapy is continued.
  • GDM is associated with a nearly 2-fold risk for postpartum depression.
  • Screen for T2DM at 6-12 weeks postpartum using 2-hour 75-g OGTT:
    • Glucose 140-199 mg/dL indicates impaired glucose tolerance (prediabetes).
    • Glucose ≥200 mg/dL indicates T2DM.
  • Continue screening women who have had GDM for T2DM using standard criteria every 3 years for life.

Patient Monitoring
During pregnancy, monitor fasting glucose at either 1-hour or 2-hour postprandial glucose levels (up to 4 times daily) until control is established; intensify therapy whenever the following targets are not consistently met: �
  • Fasting ≤95 mg/dL
  • 1-hour postmeal ≤140 mg/dL
  • 2-hour postmeal ≤120 mg/dL

Diet


  • Personalized nutrition plan based on BMI
  • Limit carbohydrates from 33 to 40% of calories.
    • Complex versus simple carbohydrates preferred
  • 3 meals plus 2 or 3 snacks per day

Patient Education


Women with GDM should receive education about potential complications (see below), the importance of glycemic control during pregnancy, their future risk of T2DM (see "Prognosis"� below), and ways to reduce that risk (see "General Prevention"� above). �

Prognosis


  • Risk of recurrent GDM in subsequent pregnancy is approximately 41%.
  • Women who have had GDM are at 7-fold increased risk for developing T2DM.
    • 1/3 will have diabetes or impaired glucose metabolism at postpartum testing.
    • 15-50% will develop T2DM later in life.

Complications


  • Maternal
    • Gestational hypertension
    • Preeclampsia
    • Cesarean delivery
    • Subsequent development of T2DM
  • Fetal
    • Macrosomia
    • Shoulder dystocia
    • Birth trauma
    • Neonatal hypoglycemia
    • Neonatal hyperbilirubinemia

References


1.American Diabetes Association. Standards of medical care in diabetes-2014. Diabetes Care.  2014;37(Suppl 1):S14-S80. �
[]
2.Committee on Practice Bulletins-Obstetrics. Practice Bulletin No. 137: Gestational diabetes mellitus. Obstet Gynecol.  2013;122(2 Pt 1):406-416. �
[]
3.Donovan �L, Hartling �L, Muise �M, et al. Screening tests for gestational diabetes: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med.  2013;159(2):115-122. �
[]
4.Hartling �L, Dryden �DM, Guthrie �A, et al. Benefits and harms of treating gestational diabetes mellitus: a systematic review and meta-analysis for the U.S. Preventive Services Task Force and the National Institutes of Health Office of Medical Applications of Research. Ann Intern Med.  2013;159(2):123-129. �
[]
5.Gui �J, Liu �Q, Feng �L. Metformin vs insulin in the management of gestational diabetes: a meta-analysis. PLoS One.  2013;8(5):e64585. �
[]

Additional Reading


  • Perinatology.com. Gestational diabetes: calculation of caloric requirements and initial insulin dose. Available at http://www.perinatology.com/calulators/GDM.htm

See Also


Diabetes Mellitus, Type 2 �

Codes


ICD09


  • 648.80 Abnormal glucose tolerance of mother, unspecified as to episode of care or not applicable
  • 648.83 Abnormal glucose tolerance of mother, antepartum condition or complication
  • V12.21 Personal history of gestational diabetes
  • 648.81 Abnormal glucose tolerance of mother, delivered, with or without mention of antepartum condition
  • 648.82 Abnormal glucose tolerance of mother, delivered, with mention of postpartum complication
  • 648.84 Abnormal glucose tolerance of mother, postpartum condition or complication

ICD10


  • O24.429 Gestational diabetes mellitus in childbirth, unsp control
  • O24.420 Gestational diabetes mellitus in childbirth, diet controlled
  • Z86.32 Personal history of gestational diabetes
  • O24.424 Gestational diabetes in childbirth, insulin controlled

SNOMED


  • 11687002 Gestational diabetes mellitus (disorder)
  • 75022004 Gestational diabetes mellitus, class A1 (disorder)
  • 472971004 History of gestational diabetes mellitus (situation)
  • 46894009 Gestational diabetes mellitus, class A2 (disorder)

Clinical Pearls


  • Screen for undiagnosed T2DM at the first prenatal visit in women with risk factors.
  • Screen for GDM at 24-28 weeks of gestation in pregnant women not previously known to have diabetes. Both one-step and two-step methods of screening are acceptable.
  • Treat all women diagnosed with GDM using dietary therapy and, if necessary, medication. Metformin, glyburide, and insulin are first-line options if pharmacotherapy is needed.
  • Screen women who have had GDM for T2DM 6-12 weeks postpartum and every 3 years thereafter.
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