Gestational Diabetes

Benjamin Byers, D.O., FACOG Center for Maternal and Fetal Care Bryan Physician Network Outline • Definition – Prevalence – Risk factors – complications • Diagnosis • Management – Nonpharmacologic – Pharmacologic – Antepartum surveillance – Delivery Introduction • is accompanied by insulin resistance – Growth hormone – Corticotropin-releasing hormone – Placental lactogen – Progesterone

• Assure that the fetus has an adequate supply of nutrients • Diabetes develops during pregnancy in women whose pancreatic function is insufficient to overcome the insulin resistance associated with the pregnant state. Definition and prevalence • mellitus (GDM) – Carbohydrate intolerance – Diagnosed during pregnancy

• Prevalence – Varies in direct proportion to the prevalence of type 2 DM in the population – 90% of DM in pregnancy is GDM – Ethnicity variance: Hispanic, African American, Asian, Native American – Obesity – Increasing prevalence: • Obesity, sedentary lifestyle, delayed childbearing • 5-6% of in the USA

• Correlates with the prevalence of type 2 DM. NE

“Diabetes Belt” Maternal complications • Gestational hypertension and preeclampsia • (high ) • Cesarean delivery • 50% risk of developing overt DM later in life Fetal complications • Miscarriage • Congenital anomalies • Macrosomia: > 4500 grams • Neonatal hypoglycemia • Hyperbilirubinemia • Operative delivery • Shoulder dystocia • Birth trauma • Neonatal respiratory problems • Perinatal mortality Polyhydramnios: excessive amniotic fluid Congenital Anomalies

Caudal Regression Syndrome from untreated diabetes in pregnancy Also known as sacral agenesis Macrosomia Macrosomia Operative delivery Forceps, Vacuum, Cesarean

Facial palsy from forceps delivery Subgaleal hemorrhage from vacuum delivery. This baby died at 2 weeks of life. Necrotizing fasciitis from infected cesarean incision. -30-50% mortality This patient died. Shoulder dystocia

Erb’s palsy from brachial plexus injury secondary to shoulder dystocia

Risk factors for GDM

• Previously diagnosed with GDM: 33-50% recurrence risk • Impaired glucose metabolism • Obesity: BMI 30 kg/m2 • Ethnicity: Hispanic-American, African-American, Native American, Asian, Pacific Islander • Maternal age >25 • Previous infant birth weight >9 lbs. • Previous stillbirth or malformed infant

• The above patients may be candidates for early screening for GDM (1st or early 2nd trimester)

If gestational diabetes mellitus is not diagnosed, blood glucose testing should be repeated at 24–28 week of gestation. How is GDM diagnosed? • ALL pregnant women should be screened* • Historical – Patient’s family history, personal medical history and OB history – 1973: O’Sullivan proposed the 50g, one hour glucose tolerance test • 95% of OB providers use for ALL their patients Two different approaches to diagnosis of GDM • Two-step approach • One-step approach – Traditional method in – Proposed in 2010 USA – 75 gram test – Step 1… 50 grams – Significant increase in • Screening test GDM diagnosis • If “passes” then no – Not currently GDM recommended by ACOG or • If “fails” then might be SMFM GDM… – Step 2…100 grams • Diagnostic test • GDM diagnosed if 2 of 4 values are elevated. Two-step approach Either one is okay!

Select one for your practice/group

14-23% of patients will “fail” and need to perform Step 2 Either one is okay!

Select one for your practice/group One-step approach • 2010, International Association of Study Group (IADPSG)* • Based on data from the Hyperglycemia and Adverse Pregnancy Outcome study • Endorsed by the American Diabetes Association (ADA) • 18% of the US population would test positive for GDM * National organizations • American College of Obstetricians and Gynecologists (ACOG) – Two step • International Association of Diabetes and Pregnancy Study Groups (IADPSG) – One step • American Diabetes Association (ADA) – One or two step • World Health Organization (WHO) – One step • Canadian Diabetes Association (CDA) – Two step preferred; one step okay • The Endocrine Society – One step • Australian Diabetes in Pregnancy Society (ADIPS) – One step

So which one to use? • 2013: Eunice Kennedy Shriver National Institute of Child Health and Human Development Consensus Development Conference – Continue the two-step approach – No evidence that the one-step approach would lead to clinically significant improvements in maternal or newborn outcomes – Significant increase in healthcare costs • 15-20% prevalence – ACOG supports the above – More studies needed to confirm superiority (of the one step)

National Institutes of Health Consensus Development Conference Statement. Diagnosing Gestational Diabetes Mellitus, March 4-6, 2013. Obstet Gynecol, Aug 2013 Dr. Byers’s method “I can’t drink that stuff” • Nausea and vomiting • Dumping syndrome* • Periodic fasting and postprandial finger sticks • Fasting plasma glucose >85 • Other methods of high glucose sources – Jelly beans – Soft drinks – Not endorsed by the ADA or ACOG So your patient has GDM… now what? • Are there benefits to treating GDM?

• Are there risks to treating GDM?

• 2005: Australian Carbohydrate Intolerance Study in Pregnant Women trial – Randomized trial for GDM – Treatment of GDM resulted in significant reduction in the composite primary outcome • Perinatal death • Shoulder dystocia • Birth trauma (fracture and nerve palsy) • Large-for-gestational-age (LGA) fetuses Maternal preeclampsia • 2009: Eunice Kennedy Shriver NICHHD/Maternal-Fetal Medicine Network – Randomized trial of 958 women with GDM – Decreased frequency in the treatment-arm • LGA infants • Neonatal fat mass • Cesarean delivery • Shoulder dystocia • Hypertensive disorders • 2013: Systematic review and meta-analysis – Treatment of GDM with nutrition therapy, self blood glucose monitoring, and insulin (if needed) – Reductions in • Preeclampsia (RR 0.62) • Birth weight >4000 grams (RR 0.50) • Shoulder dystocia (RR 0.42) – Only potential harm • Increased number of prenatal visits

Hartling L et al. Benefits and harms of treating gestational diabetes mellitus. Ann Intern Med 2013; 159:123. Optimal glycemic control = Better maternal and fetal outcomes

Suboptimal glycemic control = Worse maternal and fetal outcomes • Risks for treating GDM – Insulin and oral hypoglycemic medications • Hypoglycemia – Increased pregnancy surveillance  false positive fetal testing  increased labor induction  failed labor induction  cesarean delivery

– Postpartum hemorrhage, infection, hysterectomy, thromboembolism, previa, uterine rupture – Increased NICU admission rate • Separates mom and baby, interrupts bonding • 2013: ACOG practice bulletin #137

“… women in whom GDM is diagnosed should be treated with nutrition therapy and, when necessary, medication for both fetal and maternal benefit.” How should blood glucose be monitored? • No consensus • General recommendations based on expert opinion – Finger stick blood glucose four times daily – Fasting, postprandial each meal* – Goal blood glucose values: • Fasting: 95 mg/dl • 1 hour: 140 mg/dl • 2 hour: 120 mg/dl

De Veciana et al. Postprandial versus pre-prandial blood glucose monitoring in women with gestational diabetes requiring insulin therapy. N Engl J Med 1995; 333:1237 • Optimal glycemic control on diet alone? – Consider decreasing the frequency of self blood glucose checks • Increase patient convenience • Decreased health care costs • Every third day is reasonable

Mendez-Figueroa H, et al. Comparing daily versus less frequent blood glucose monitoring in patients with mild gestational diabetes. J Matern Fetal Neonatal Med 2013; 26: 1268.

What Nonpharmacologic treatments are effective? • Nutrition therapy goals – Achieve normoglycemia – Prevent ketosis – Provide adequate weight gain – Contribute to fetal well-being

• Nutritional counseling by registered dietician – Individualized treatment plan based on BMI • Three basic components – Caloric allotment • 1800-2500 kcal/day* – Carbohydrate intake – Caloric distribution

• Carbohydrates: 33-40% • Protein: 20% • Fat: 40% • Complex carbohydrates preferred over simple carbohydrates* – Less likely to cause postprandial hyperglycemia

• Three meals per day • Two to three snacks per day

• Moderate exercise also recommended • http://www.perinatology.com/calculators/GDM.htm • Pay attention to subsequent changes in weight • Retrospective cohort study of 31,000 women with GDM – Appropriate weight gain: optimal outcomes – Excessive weight gain: increase in • LGA • Preterm birth • Cesarean delivery

Institute of Medicine, Food and Nutrition Board, Committee on Nutritional Status During Pregnancy, part I; National Academy Press, Washington, DC 2000 What pharmacologic treatments are effective?

• Medications utilized when nutrition therapy fails to achieve normoglycemia • No consistent threshold value at which clinicians should initiate medical therapy*

• Insulin therapy – Historical treatment • Oral agents – May now be used as first-line therapy Insulin • Does not cross the placenta • 0.7-1.0 units/kg daily in divided doses • Combination of intermediate-acting (NPH) and short (regular) or rapid (lispro, aspart) acting insulin*

• http://www.perinatology.com/calculators/GDM.htm { Oral antidiabetic agents • Increased usage in the USA • Not FDA approved for GDM • Glyburide and metformin most common • No significant difference in glucose levels when compared in insulin • No evidence for short term adverse outcomes • Both can be considered for glycemic control in women with GDM

Gestational Diabetes Mellitus. ACOG PB 137, 2013 Glyburide • Sulfonylurea • Increases insulin secretion from the pancreatic beta cells and increases insulin sensitivity in peripheral tissues • Do not use if sulfa allergy! • 20-40% will “fail” and need insulin* • 2.5-20 mg daily, typically BID Metformin • Biguanide • Inhibits hepatic gluconeogenesis and glucose absorption • Stimulates glucose uptake in peripheral tissues • Typically used in two scenarios*:

Pregestational DM Polycystic ovarian syndrome (PCOS) Continue metformin Continue metformin, but DC Add insulin if needed after 1st trimester Glyburide vs. metformin

• RCT • Glyburide: 16% eventually needed insulin • Metformin: 35% eventually needed insulin • “Glyburide may be superior to metformin in achieving satisfactory glycemic control.”

Moore et al. Metformin compared with glyburide in gestational diabetes: a randomized controlled trial. Obstet Gynecol 2010; 115:55. However… • Glyburide does cross the placenta • Umbilical cord analysis: no detectable glyburide

• So… – No short term adverse effects – Unknown long-term effects* Do I need to “watch” the GDM pregnancies closer? • Antepartum fetal testing (APFT) recommended for pregestational DM • GDM with good control – APFT not needed • GDM with suboptimal or poor control – APFT indicated My practice • Diet controlled GDM (A1 GDM) – Evaluate glucose logs each visit – Fundal height measurements for fetal growth – Await spontaneous labor – APFT if undelivered by their due date • Medication-controlled GDM (A2 GDM) – Evaluate glucose logs each visit – Serial US for fetal growth (4-6 weeks) – APFT 32 weeks until delivery – Delivery 39 weeks

Rosenstein et al. The risk of stillbirth and infant death stratified by in women with gestational diabetes. Am J Obstet Gynecol 2012; 206:309e1 APFT 32 weeks 1. 2x/week 2. Amniotic Fluid Index (AFI) ultrasound 1x/week What about delivery? • Macrosomia • Birth trauma • Shoulder dystocia

• Assess fetal growth in late 3rd trimester • Vaginal delivery in most cases

• ACOG PB 137 “…reasonable to recommend that women with GDM be counseled regarding the option of a scheduled cesarean delivery when the estimated fetal weight is 4,500 or more.” Glycemic monitoring during delivery • Finger stick blood glucose every 2 hours while in labor • Goal glucose level: 70-110 • If >120: insulin infusion – Regular insulin: start at 1 unit/hour – Check blood glucose every hour if insulin infusion After delivery and beyond • Most women with GDM are normoglycemic after delivery

• High risk of GDM in future pregnancies

• High risk of overt DM later in life (50%)

• All women with GDM should undergo a glucose tolerance test 6-12 weeks postpartum

The future… • Develop an international diagnostic approach – Patient benefit • Would the increase in diagnosis of GDM by the IADPSG criteria lead to improved maternal-fetal outcomes? – Cost benefit, cost effectiveness, cost utility – Psychological and emotional outcomes – Long-term maternal-fetal health concerns Summary points • Level A evidence (best) – If GDM diagnosed, should treat with nutrition and medical therapy if needed – Insulin or oral agents may be used, if needed

• Level B evidence (better) – All pregnancies should be screened for GDM – If fetal weight >4500 grams, consider cesarean

• Level C evidence (good) – 1 hour test: 135 or 140 can be used as cut-off – 3 hour test: Carpenter Coustan or NDDG values – Glucose surveillance recommended – Good glycemic control: no need to deliver early – 6-12 weeks postpartum: screening for DM recommended Thank You