Diabetes and pregnancySTACY STREHLOW, MD

BAYLOR COLLEGE OF MEDICINE

26 JAN 2020

Pregestational diabetes

14.9 million women in the US have diabetes3-7% of reproductive-aged women have diabetes1-2% of pregnancies complicated by pregestational diabetesMore than 50% of women with gestational diabetes will develop type 2 diabetes

ACOG PB #201, 2018

Pregestational diabetes

Diabetes diagnosed before pregnancy orDiabetes diagnosed at <20 weeks’ gestation◦ Hgb A1C ≥ 6.5%◦ Fasting glucose ≥ 126 mg/dL◦ 2hr glucose ≥200mg/dL

ACOG PB #201, 2018

Pregestational diabetes95% type 2 diabetes◦ Peripheral insulin resistance◦ Obesity◦ History of gestational diabetes◦ Higher insulin requirement

5% type 1 diabetes◦ Autoimmune disease with destruction of pancreatic beta cells

which produce insulin

ACOG PB #201, 2018

Glucose levels in normal pregnancy

Gestational diabetesDiagnosed after screening glucose test

◦ All pregnant women at 24-28 wks◦ High-risk women at 1st prenatal visit

2-step approach:◦ 50 g, 1-hr glucola (screening)◦ 100 g, 3-hr GTT (diagnostic)

Diagnosis◦ If 1-hr ≥ 130-140 mg/dl 3hr GTT ◦ If 1-hr ≥ 200mg/dl diagnosis made of GDM

DiagnosisIn general, a woman when tested that has a random of > 200 mg/dL, fasting > 126 mg/dL or a 2 hour > 200 mg/dL is overt (or pre-gestational)

Most providers opt not to follow up with a 3-hour GTT.

3 hr Glucose Tolerance Test

Timing NDDG C and CFasting 105 95

1 hr 190 1802 hr 165 1553 hr 145 140

NDDG:NATIONAL DIABETES DATA GROUP; CANDC: CARPENTER AND COUSTAN

100 gm glucose load

>2 thresholds met or exceeded to diagnose GDM

Risk factors for early diabetes screeningBMI >25 and >1 additional risk factor◦ Physical inactivity◦ First-degree relative with DM◦ High-risk race/ethnicity (African American, Latino, Native American, Asian America, Pacific

Islander)◦ Prior birth of infant weighing >4,000 g (~9 lbs)◦ Prior h/o GDM◦ CHTN

Risk factors for early diabetes screening◦ HDL <35 mg/dL, triglyceride >250 mg/dL◦ PCOS◦ A1C > 5.7%, impaired glucose tolerance, impaired fasting glucose on prior testing◦ Other clinical conditions associated with insulin resistance (pre-pregnancy BMI >40,

acanthosis nigricans)◦ h/o cardiovascular disease

If diabetes not diagnosed, GDM screening at 24-28 wks

Management

Medical nutrition therapy with a carbohydrate-controlled diet◦ CDE consultation if possible

Daily exerciseGlucose checks fasting and 2 hours post-meals◦ Insulin if glucose > recommended goals◦ Continuous glucose monitoring alternatively

ACOG PB #201, 2018

ManagementTarget glucose levels◦ Fasting plasma glucose: 95 mg/dL◦ 2-hr PP plasma glucose: 120 mg/dL

ACOG PB #201, 2018

Dietary ManagementNutritional counseling by registered dietician

Food log

Caloric requirements◦ Normal body weight: 30-35 kcal/kg/d◦ <90% desirable body weight: 30-40 kcal/kg/d◦ >120% desirable body weight: 24 kcal/kg/d

Diet◦ 40-50% carbohydrates◦ 20% protein◦ 30-40% unsaturated fat

Dietary ManagementCalorie intake◦ 10-20% breakfast◦ 20-30% lunch◦ 30-40% dinner◦ 30% snack (bedtime-to avoid nocturnal hypoglycemia)

Management

Insulin is first-line medicationRapid-acting with meals – insulin lispro (Humalog) or insulin aspart (Novolog)◦ Regular insulin is short-acting and not recommended

Longer-acting daily – isophane insulin (NPH), insulin glargine (Lantus), insulin detemir (Levemir)Subcutaneous insulin pump (rapid-acting insulin)

ACOG PB #201, 2018

Insulin TypesInsulin does not cross placenta

Type of insulin

Onset of action

Peak Duration

Humalog (Lispro) 1-15 min 1-2 hr 4-5 hr

Regular 30-60 min 2-4 hr 6-8 hrNPH 1-3 hr 5-7 hr 13-18 hr

Detemir(Levemir, Lantus)

1-3 hr Minimal at 8-10 hr

18-26 hr

New Insulin StartInsulin requirements increase throughout pregnancy, most markedly between 28-32 wks◦ 1st trimester: 0.7-0.8 U/kg/day

◦ 2nd trimester: 0.8-1 U/kg/day

◦ 3rd trimester: 0.9-1.2 U/kg/day

Adjust insulin by 20% in response to hyper- or hypoglycemia

New Insulin Start - example 1

2/3 NPH + 1/3 Reg24 u NPH + 14 u Reg

2/3 total dose AM38 u

1/2 NPH + 1/2 Reg9 u NPH + 9u Reg

1/3 total dose PM18 u

70 kg x 0.8 uTotal 56 u/day

New Insulin Start - example 270 kg x 0.2u/kg = 14u

◦Lantus or Levemir 14u daily

◦Add Humulin 4u/meal if postprandial hyperglycemia

◦Adjust insulin by 20% in response to hyper- or hypoglycemia

What about oral medication?

Glyburide is no longer recommended as a first-line agent◦ Neonatal macrosomia, hypoglycemia have been found to be

more common

Metformin – depends on whom you ask◦ ACOG ‘metformin is a reasonable alternative choice…’◦ SMFM recommends first-line

ACOG PB #201, 190 2018, 2019; SMFM STATEMENT 2018

Oral Medications for GDMboth cross placenta

METFORMINBiguanide

Neonatal outcomes similar to those treated with insulin

26-46% require insulin

Dosing: 500 mg XR qhs start, increase to max of 2000 mg/day

GLYBURIDESulfonylurea

Worse neonatal outcomes compared to insulin: higher rates of hypoglycemia, macrosomia

4-16% require insulin

Dosing: 2.5-20 mg/day in divided doses

-Both cross placenta; insulin does not-No long-term data on exposed offspring

Management – Pregestational diabetes

Anatomic survey at 18-20wFetal echocardiogram if Hgb A1C is elevated (>6.5%)Serial ultrasounds for fetal growthAntenatal testing at 32+ weeks’Delivery at 39w◦ 34-39w with end-organ damage

ACOG PB #201, 2018

Timing of Delivery – Pregestational diabetes

Timing of Delivery

Well controlled

39-40 weeks

+ VascularDisease

37-39 weeks

Poor control

34-39 weeks

Risk of prematurity

Risk of IUFD

Timing of Delivery - GDM Condition Suggested

Specific TimingDiet-only GDM 39 0/7 – 40 6/7

GDM on medication, well-controlled

39 0/7 – 39 6/7

GDM, poor control 37 0/7 – 38 6/7

Antepartum ManagementPREGESTATIONAL DM

Medical management:◦ Insulin ◦ Limited data on oral agents in Type

2 DM

OB visit every 1-2 weeks, then weekly after 28-30 weeks

Comprehensive ultrasound/fetal echo 18-20 weeks

BPP begins at 32 wks

Fetal weight estimate near delivery –every 4 weeks

GESTATIONAL DMTrial of nutrition and exercise therapy

Medical management:◦ Insulin or oral medications

BPP with medication-controlled GDM begins at 32 wks

Fetal weight estimate near delivery –every 4 weeks

Offer cesarean delivery if EFW >4500 gms

Increased risk of:Preeclampsia

Polyhydramnios

Fetal macrosomia

Birth trauma

Operative delivery

Perinatal mortality

Neonatal metabolic complications (i.e. hypoglycemia, hyperbilirubinemia)

Macrosomia

Major impact of GDM is macrosomia

Erb’s Palsy

Risk reductionTreatment is associated with a significant reduction in the rate of:

◦ Perinatal death

◦ Shoulder dystocia

◦ Birth trauma, including fracture or nerve palsy (composite

outcome)

Obstetric complications

Primary CesareanSpontaneous preterm laborPolyhydramniosPreeclampsiaHyperglycemia in labor

ACOG PB #201, 2018

Intrapartum management

Insulin infusion (‘drip’) rarely needed outside of type 1 diabetesCheck glucose every 2 hours in latent phase and hourly in laborInsulin pump usually discontinued during labor◦Can continue basal infusion during labor for women with insulin pump

ACOG PB #201, 2018

Postpartum

Encourage breastfeedingMetformin may be used while breastfeedingEncourage long-acting reversible contraception (LARC) e.g. IUD, Nexplanon◦ Low-dose OCPs can be used if women have no vascular

disease and don’t smoke

ACOG PB #201, 2018

Postpartum management

Pregestational diabetics:◦ resume pre-pregnancy insulin dose

or ◦ use 50% current dose

Gestational diabetics:◦ Stop medication◦ Screen at 6-12 weeks’ postpartum

ACOG PB #201, 2018

Postpartum ScreeningPostpartum screening at 6–12 weeks for all women with GDM ◦ Fasting plasma glucose test or 75-gm, 2-hr GTT◦ 1/3 will have DM or impaired glucose metabolism◦ 15–50% develop type 2 DM later in life

◦ 7-fold increased risk

Diabetes – postpartum/pre-conceptionAll pre-gestational diabetics (type 1 and type 2) SHOULD have preconception appointments with GC and MFM to discuss teratogenicity of hyperglycemia and obstetrical complications related to DM.

GOAL is < 6.4 for diabetics

Re-check every 3 months until at goal

Antenatal management – special concerns

If glucose is >200, then urine ketones should be checked◦ DKA possible with type 1 or type 2 diabetes

For women with type 1 diabetes or women with hypoglycemic episodes:◦ Glucose tablets available◦ Glucagon on hand◦ Medical bracelet

ACOG PB #201, 2018

Antenatal management – special concerns

Caution with the administration of antenatal steroidsPer WHO, not contraindicated at 34-37wGlucose increases ~12 hours after first dose of steroids and can be elevated for 3-7 daysConsider inpatient monitoring of glucose for 3-5 days post-steroids in high-risk patients

ACOG PB #201, 2018; WHO 2015

http://perinatology.com/calculators/Insulin%20during%20Betamethasone.htm

Other considerations

Thyroid disease present in up to 40% of women with DM 1◦ TSH testing

Increased risk of neural tube defect◦ Supplement folic acid, 800-1000mcg daily

Increased risk of preeclampsia◦ Low-dose aspirin (81mg) daily 12+ weeks’

ACOG PB #201, 2018

Maternal complications

Diabetic retinopathy◦ May worsen with rapid correction of glucose◦ Eye exam in the first trimester

Diabetic nephropathy◦ 5-10% of diabetic pregnancies◦ Higher risk for preeclampsia, fetal growth restriction◦ 24h urine in the first trimester

ACOG PB #201, 2018

Maternal complicationsHypertension◦ 5-10% of diabetic pregnancies◦ Comorbidity or a result of nephropathy

Acute MI◦ Rare but higher risk due to coronary artery disease◦ EKG in first trimester if diabetes >10 years

Diabetic neuropathy◦ N/V due to gastroparesis

ACOG PB #201, 2018

Maternal complications - DKA

Diabetic ketoacidosis◦ Most common with DM 2 but can occur with DM 1◦ Seen in 5-10% of DM pregnancies

Abdominal pain, N/V, altered mental statusLow arterial pH (<7.3), low bicarb (<15 mEq/L), elevated anion gap, urine & serum ketones

ACOG PB #201, 2018

Copyrights apply

Maternal complications - DKALabs: ◦ ABG, hourly glucose, ketones, electrolytes

IV 0.9% NaCl 4-6L in first 12h◦ If serum sodium is high then switch to 0.45% NaCl◦ When glucose <200, change to 5% dextrose 0.45% NaCl

IV potassium◦20-40 mEq/hour until K>3.3 mEq/L◦20-30 mEq in each liter of IV fluid to maintain K 4-5mEq/L

ACOG PB #201, 2018

Maternal complications - DKARegular Insulin IV◦ Hold insulin until K>3.3mEq/L◦ 0.1 units/kg/hour start dose◦ Double dose until glucose decline is achieved◦ Reduce to 0.02-0.05u/kg/hr when glucose <200

Subcutaneous insulin – for mild DKA◦ Rapid-acting (Novolog, Humalog)◦ 0.3u/kg then 0.1u/kg until glucose <250◦ Patient’s long-acting insulin may be given as usually scheduled

ACOG PB #201, 2018

Maternal complications - DKA

Bicarbonate◦ For pH ≤6.9, supplement dilute NaHCO3◦ 100 mEq in 400 mL sterile water administered over 2 hours◦ Can also be used to lower potassiu,m in life-threatening

hyperkalemia (K>6.4 mEq/L)

ACOG PB #201, 2018

Fetal complications

Higher risk of complications with longer duration of diabetes, end-organ damage, or concurrent hypertensionCongenital anomalies in 6-12% of pregnanices◦ 2-3% of pregnancies with Hgb A1C 5-6%◦ 20-25% of pregnancies with Hgb A1C 10%◦ Cardiac, CNS, skeletal, renal

ACOG PB #201, 2018

Fetal complicationsHgbA1C < 8.0 -> risk 3.2%

HgbA1C >10 -> risk 24%

Preprandial glucose <120 -> risk 2%

Preprandial glucose >120 -> risk 8%

With increasing FBS there is increased risk of multiple organ system abnormalities

Common malformationsCVS (20-38%)

CNS (10-28%)

Urinary tract

GI (4-16%)

Limb (4-28%)

Spine

Face

Malformations associated with DMHeart defects Thumb defects PolydactylyEar tags Small nails ColobomasHelical pits Rib anomalies NTDMicrotia Micrognathia Imperf. anusHemivertebrae Holoprosenceph. OmphaloceleSitus inversus Renal MicrocephalyRib defects Radial hypoplasia MacrocephalyMicroophthalmia Femur hypoplasia SyndactylyCleft lip/palate Tibial hypoplasia Sacral agenesis

CVS (relative risk 3x)VSD/ASD

Dextrocardia

Cardiomyopathy/septal hypertrophy

Conotruncal abnormalities◦ Tetralogy of Fallot◦ Truncus arteriosus◦ Transposition of the great arteries

Coarctation of the aorta

CNS (relative risk 3x)Holoprosencephaly

Neural tube defects◦ Anencephaly◦ Encephalocele◦ Meningomyelocele

RenalDuplicated collecting system

Renal agenesis

Ureterocele

Hydronephrosis

Spine (relative risk >50x)Caudal regression syndrome risk 1-5/1000 in DM

◦ Spinal defects range from unilateral sacral dysplasia or agenesis to lumbosacral agenesis with limb abnormalities

◦ Often associated with GI/GU anomalies

Neural tube defect

EtiologyHyperglycemia appears to be teratogenic

Possibly due to oxidative stress – negative effect on antioxidant enzymes or genes (eg SOD)

Nutrient deficient states in membrane lipids (eg arachidonic acid, myoinositol)

Fetal complications

Fetal demiseMacrosomia◦ Shoulder dystocia

ACOG PB #201, 2018

Neonatal complicationsHypoglycemia◦ Seizures

Respiratory distress syndromePolycythemiaOrganomegalyElectrolyte disturbanceHyperbilirubinemia

ACOG PB #201, 2018

Neonatal and beyond complications

ObesityInsulin resistanceMetabolic syndromeCardiac disease

ACOG PB #201, 2018