Endocrinology | Obstetrics
Gestational Diabetes Mellitus
Background
-
Gestational diabetes mellitus is diabetes that is first diagnosed in the second or third trimester of pregnancy that is not preexisting T1DM or T2DM
- Women diagnosed with diabetes by standard diagnostic criteria in the first trimester should be classified as having preexisting pregestational diabetes
- Screening for and treating GDM reduces the risks of perinatal and long-term disease; rule out preexisting DM
- Management of gestational diabetes involves
- Frequent monitoring of blood glucose
- Individualized nutritional therapy to limit carbohydrate consumption and provide adequate nutrition to maintain appropriate weight gain
- Individualized physical activity recommendations to control weight gain and improve glucose homeostasis
- If indicated, insulin therapy; referral to a diabetic specialized center is then warranted
- Women with a history of GDM should receive lifelong screening for the development of DM or prediabetes at least every 3 years
- Women with a history of GDM found to have prediabetes should receive intensive lifestyle intervention, or metformin, to prevent the development of DM
Pathophysiology
- Pathology of Disease
- Pregnancy is a state of insulin resistance
- Increased insulin needs in pregnancy
- Insulin release is enhanced in pregnancy
- Increased insulin -> hunger-> overeating
- Insulin release decreases insulin receptors
- Control of diabetes and requirement of insulin increase during pregnancy
- Increased insulin resistance and decreased sensitivity to insulin
- Largely due to placental production of human placental lactogen (HPL) and progesterone in the 3rd trimester
- HPL blocks insulin receptors
- Other hormones that contribute include prolactin and cortisol
- Incidence, Prevalence
- 0.3-0.5% of pregnancies in the U.S. occur in women with pregestational diabetes
- About 90% of women with pregnancies complicated by diabetes have gestational diabetes
- Risk Factors
- >25 years of age
- BMI ≥25 kg/m2 (or if Asian American, BMI ≥23 kg/m2)
- Excessive weight gain during pregnancy
- History of adverse pregnancy outcomes
- Family history of DM in a first-degree relative
- High-risk ethnic groups
- Hispanic
- African
- Native American
- South or East Asia
- Pacific Islands
- Morbidity/Mortality
- Increased risk of neonatal complications, including
- Diabetic embryopathy results in pre- or post-natal mortality or disability
- Spontaneous Abortion
- Anencephaly
- Microcephaly
- Congenital heart disease
- Maternal complications
- Infection
- Infection increases the risk of developing preterm labor or diabetic ketoacidosis
- UTIs are likely to be more severe in diabetic than non-diabetic women
- Peripheral and autonomic neuropathy
- Women with neuropathy (autonomic or peripheral) are at increased risk of pregnancy complications, such as
- Hyperemesis gravidarum (related to gastroparesis)
- Hypoglycemia unawareness
- Orthostatic hypotension
- Urinary retention
- Carpal tunnel syndrome
- Cardiovascular adjustments to pregnancy may be impaired in women with diabetic neuropathy
- Cardiovascular disease
- Women with diabetes have increased risk for atherosclerosis due to diabetes and other risk factors
- HTN and preeclampsia
- Prevalence of HTN and preeclampsia is increased in pregnant patients with diabetes and is related to both
- Pregestational HTN
- Vascular disease
- Insulin resistance appears to increase the risk of preeclampsia, even in absence of overt diabetes
- Diabetic nephropathy
- Presence of diabetic nephropathy and its acceleration are a concern for both fetus and mother
- Both microalbuminuria and overt nephropathy are associated with increased rate of preterm birth
- HTN and preeclampsia can also lead to fetal growth restriction and, rarely, fetal or maternal death
- Diabetic retinopathy
- Worsens in some women during pregnancy
- Although not likely to develop de novo in women with no retinopathy before pregnancy
- Related to the duration of diabetes and to the degree of glycemic control
- After pregnancy, milder forms of diabetic retinopathy typically regress
- Some women with severe forms of diabetic retinopathy may show persistence or progression
Diagnostics
- History
- Complete H&P exam, including
- Thyroid exam
- History of duration and type of diabetes
- History of acute complications
- Chronic complications
- Current and past glucose management history
- Physical activity level
- Preexisting medical conditions
- Gynecological and obstetric history
- GDM in a previous pregnancy
- Family history of GDM
- Physical Examination
- Document BMI
- Dilated, comprehensive eye exam by an ophthalmologist to detect retinopathy
- Screening for and Diagnosing GDM
- One-step strategy
- At 24-28 weeks gestation, perform OGTT after a minimum of 8 hours of fasting
- 75 g OGTT with plasma glucose measurement when the patient is fasting at hour 1, hour 2
- Diagnosis of GDM made when
- Fasting BG: 92 mg/dL (5.1 mmol/L)
- 1 hr: 180 mg/dL (10.0 mmol/L)
- 2 hr: 153 mg/dL (8.5 mmol/L)
- Two-step strategy (supported by the ACOG)
- At 24-48 weeks gestation, perform non-fasting 50 g GLT with a plasma glucose measurement after 1 hour
- If plasma glucose at 1 hour is ≥130 mg/dL (7.2 mmol/L), proceed with 100 g OGTT
- While the patient is fasting perform 100 g OGTT; measure fasting glucose level at hour 1, hour 2, and hour 3
- Diagnosis of GDM is made when at least 2 of following are met or exceeded (Carpenter/Coustan Criteria)
- Fasting BG: 95 mg/dL (5.3 mmol/L)
- 1 hr: 180 mg/dL (10.0 mmol/L)
- 2hr: 155 mg/dL (8.6 mmol/L)
- 3hr: 140 mg/dL (7.8 mmol/L)
OR
- Diagnosis of GDM is made when at least 2 of following are met or exceeded (NDDG, National Diabetes Data Group Criteria)
- Fasting BG: 105 mg/dL (5.8 mmol/L)
- 1 hr: 190 mg/dL (10.6 mmol/L)
- 2 hr: 165 mg/dL (9.2 mmol/L)
- 3 hr: 145 mg/dL (8.0 mmol/L)
- Other laboratory investigations to consider
- HBA1C
- May require more frequent monitoring (monthly) due to RBC kinetic alternation during pregnancy
- Target < 6%
- LFT
- Urine albumin
- Serum creatinine
- Lipid profile
- TSH
Therapeutics
- Lifestyle modifications (first-line therapy)
- Physical activity regimen
- 3-4 days per week for 20-30 min, such as walking
- Medical Nutrition Therapy
- An individualized plan should be developed by a registered dietitian with familiarity in the management of GDM
- Plan should provide adequate calorie intake to
- Promote fetal/neonatal and maternal health
- Achieve glycemic goals, and
- Promote appropriate gestational weight gain
- No definitive research identifying a specific optimal calorie intake for women with GDM or suggests that their calorie needs are different from those of pregnant women without GDM
- Plan should be based on a nutrition assessment with guidance from the Dietary Reference Intakes (DRI)
- DRI for all pregnant women recommends the following
- A minimum of 175 g of carbohydrate
- A minimum of 71 g of protein, and
- 28 g of fiber
- Glucose monitoring
- Fasting and postprandial monitoring recommended in GDM
- BG targets in GDM (similar for women with T1DM and T2DM)
- Fasting: <95 mg/dL (5.3 mmol/L) and either
- One-hour postprandial <140 mg/dL (7.8 mmol/L)
or
- Two-hour postprandial <120 mg/dL (6.7 mmol/L)
- A1C targets in pregnancy: A1C 6–6.5% (42–48 mmol/mol)
- A target of <6% (42 mmol/mol) may be optimal if this can be achieved without significant hypoglycemia
- A target of <7% (53 mmol/mol) if it is necessary to prevent hypoglycemia
- Insulin
- Preferred agent in GDM if pharmacological therapy is indicated
- Referral to a specialized center offering team-based care is essential for insulin guidance and patient education
- Generally, a smaller proportion of the TDD should be administered as basal insulin (<50%) and a greater proportion (>50%) as prandial insulin
- Late in the third trimester, there is often a leveling off or small decrease in insulin requirements
- Commonly used insulin agents in GDM (short-acting analogs preferred)
- Lispro
- Aspart
- Regular insulin
- Glargine
- Detemir
- For insulin pharmacokinetic data, click here
- Oral glycemic therapy
- For patients unable to receive insulin, metformin or glyburide may be considered
- Not FDA approved for GDM
- Counsel on risks
- Long-term effects on offspring is unknown
- Metformin 500 mg nightly for 1 week, increase to 500 twice daily
- Glyburide 2.5-20 mg per day in divided doses
- Intrapartum insulin management
- Latent labor: insulin can be given with goal of blood glucose between 70 and 90 mg/dL
- Active labor: insulin resistance rapidly decreases, and insulin requirements fall rapidly
- Glucose should be infused at a rate of 2.55 mg/kg per min and capillary blood glucose be measured hourly
- For blood glucose values of 120 mg/dL or greater, give rapid-acting insulin subcutaneously or regular insulin intravenously until blood glucose value falls to 70-90 mg/dL
- C-section: if Cesarean delivery is planned
- Bedtime NPH insulin dose may be given on the morning of surgery and every eight hrs thereafter if surgery is delayed
- Induction: T1DM or T2DM in whom labor is induced should receive either no morning insulin or only a small dose of intermediate-acting insulin
- Postpartum insulin management
- Insulin requirements drop sharply after delivery
- Drop in placental growth hormone
- New mother may not require insulin for 24-72 hrs
- Insulin requirements should be recalculated at this time based on the postpartum weight
- Postpartum calorie requirements are approximately 25 kcal/kg per day, and somewhat higher (27 kcal/kg per day) in lactating women
- All women should be supported in attempts to nurse their babies due to immunological and nutritional benefits
- GDM and HTN management
- Target SBP 110-129 mmHg and DBP 65-79 mmHg
- Lower pressures may be associated with impaired fetal growth
- ACEI and ARB contraindicated in pregnancy
- Chronic diuretic use in pregnancy associated with reduced uteroplacental perfusion
- HTN agents considered effective and safe in pregnancy
- Fetal Monitoring
- If BG well controlled on diet alone
- Begin at >32 weeks gestation
- If BG poorly controlled on medication without comorbidities
- Begin fetal monitoring earlier based on local practice
- Include amniotic fluid volume assessment
- Delivery
- If BG well controlled on diet alone
- Deliver at >39 weeks with expectant management at 40 weeks and 6 days with antepartum testing
- If BG well controlled on medication
- Deliver at 39 weeks 0 days - 39 weeks 6 days
- If BG poorly controlled
- Delivery between 37 weeks 0 days - 38 weeks 6 days may be considered
- If abnormal fetal testing or failure of in-hospital glycemic control
- Delivery at 34 weeks 0 days - 36 weeks 6 days
- If estimated fetal weight ≥4500 grams
- Counsel regarding benefits and risks from scheduled cesarean section
Postpartum Follow-Up
- Reassess need for insulin and non-insulin agents
- Screen for diabetes every 1-3 years depending on risk factors; utilize OGTT over A1C
- GDM patients are at increased risk for developing DM
- Encourage healthy lifestyle changes, weight loss
- Contraception evaluation, especially for prediabetics and diabetics
- Patients newly diagnosed with prediabetes
- Consider intensive lifestyle intervention and/or metformin to prevent the development of DM
Screening
- USPSTF
- The USPSTF recommends screening for gestational diabetes mellitus (GDM) in asymptomatic pregnant women at or after 24 weeks of gestation
- The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for GDM in asymptomatic pregnant women before 24 weeks of gestation
- ADA
- Screen all females as part of preconception counseling/testing for gestational diabetes mellitus at 24–28 weeks of gestation in pregnant women not previously known to have diabetes
- ACOG
- Screen all females if the following are met
- Patient is overweight with BMI of 25 (or 23 in Asian Americans), plus one of the following
- Physical inactivity
- Known impaired glucose metabolism
- Previous pregnancy history of
- GDM
- Macrosomia (≥4000 g)
- Stillbirth
- Hypertension (140/90 mm Hg or being treated for hypertension)
- HDL cholesterol ≤35 mg/dl (0.90 mmol/L)
- Fasting triglyceride ≥250 mg/dL (2.82 mmol/L)
- PCOS, acanthosis nigricans, nonalcoholic steatohepatitis, morbid obesity and other conditions associated with insulin resistance
- A1C ≥5.7%, impaired glucose tolerance or impaired fasting glucose
- Cardiovascular disease
- 1st-degree relative (parent or sibling)
- Ethnicity of African American, American Indian, Asian American, Hispanic, Latina, or Pacific Islander
References
- American Diabetes A. Standards of Medical Care in Diabetes-2018 Abridged for Primary Care Providers. Clin Diabetes. 2018;36(1):14-37.
- American Diabetes Association. Preconception care of women with diabetes. Diabetes Care 2004; 27 Suppl 1:S76.
- ACOG Practice Bulletin #60: Pregestational Diabetes Mellitus. Obstet Gynecol 2005; 105:675.
- Jovanovic, L, Peterson, CM. Optimal insulin delivery for the pregnant diabetic patient. Diabetes Care 1982; 5 Suppl 1:24.
- Committee on Practice B-O. ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018;131(2):e49-e64.
- Langer O, et al, A Comparison of Glyburide and Insulin in Women with Gestational Diabetes Mellitus. NEJM 2000;343:1134-1138.
- Gabbe SG, Graves CR, Management of diabetes mellitus complicating pregnancy. American College of Obstetricians and Gynecologists, 2003;102:857-868.
- Kremer CT, Duff PG, Glyburide for the Treatment of Gestational Diabetes. American J of Obstetrics and Gynecology 2004;190:1438-9.
- Chmait R, et al. Prospective Observational Study to Establish Predictors of Glyburide Success in Women with Gestational Diabetes Mellitus. J of Perinatology 2004;1-6.
- Crowther CA, et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Eng J Med 2005;352:2477-86.
Contributor(s)
Reviewed/Updated: June 2018