Diabetes in Pregnancy

Table Of Contents

Overview
Pregestational (Overt) Diabetes
Gestational Diabetes

Overview

The goal of managing diabetes in pregnancy includes providing necessary nutrients for the mother and fetus, controlling glucose levels, and preventing starvation ketosis. Women without persistent fasting hyperglycemia (A1) can be put on diet restriction.

Priscilla White Classification of Obstetric Diabetes

Gestational Diabetes

Class	Onset	Fasting Plasma Glucose	2-hour postprandial glucose	Tx
A1	Gestational	<5.8 mmol/L	< 6.7 mmol/L	Diet
A2	Gestational	> 5.8 mmol/L	> 6.7 mmol/L	Insulin or OGLAs

Overt diabetes (diagnosed before pregnancy)

Class	Vascular Disease	Onset	Duration	Therapy
B	None	> 20	< 10	Insulin
C	None	10 – 19	10 – 19	Insulin
D	Benign retinopathy	< 10	> 20	Insulin
F	Nephropathy	Any	Any	Insulin
R	Proliferative retinopathy	Any	Any	Insulin
H	Coronary artery disease	Any	Any	Insulin
T	Renal transplant	Any	Any	Insulin

Pregestational (Overt) Diabetes

Pregestational diabetes is type 1 or type 2 diabetes that exists before pregnancy. It requires different tx and has different complications when compared to GDM. All women are put on 400mcg pre-conceptional folate. Check medications and make sure to d/c ACEis/ARBs etc. Diagnosis of overt diabetes in pregnancy is made with random glucose of > 11.1 mmol/L (close to the renal threshold) + symptoms of polydipsia, polyuria, and weight loss orKetoacidosis.

The incidence of pregestational diabetes is increasing. This is the most common form of diabetes that you will come across. T2DM > T1DM.

Insulin-dependent (T1DM) vs Non-insulin-dependent (T2DM)

	T1DM	T2DM
Genetic locus	HLA-D Chromosome 6	Chromosome 11
Age at onset	Young (<40)	Older (>40)
Habitus	Normal to wasted	Normal to high
Plasma glucagon	High, suppressible	High, resistant
Acute complications	DKA	HHS
Concordance in monozygotic twins	<50%	100%
Insulin therapy	Responsive	Responsive to resistant
Sulfonylurea therapy	Unresponsive	Responsive

Adverse outcomes are associated with poor pre-pregnancy and early pregnancy HbA1C levels

HbA1C	Risk of congenital malformations
< 7%	3% risk
7-9%	14% risk
9-11%	23% risk
> 12%	25% risk

Obstetric complications
- Polyhydramnios
- Pre-eclampsia/eclampsia
- SAB
- Infection
- Postpartum haemorrhage
- Increased C-section risk
Maternal complications
- Diabetic emergencies
  - Hypoglycemia
  - DKA
  - Diabetic coma
- Vascular/end-organ involvement
  - Nephropathy
  - Neuropathy
  - Retinopathy
  - Cardiac
  - Gastroenteropathy
Fetal complications
- Fetal Macrosomia (leading to traumatic delivery, shoulder dystocia, Erb’s palsy)
- “Unexplained fetal” demise (need to be delivered at exact term)
- Spontaneous abortion
- Congenital malformations
  - Congenital Heart Defects (Most common malformations – TGA w/w/o VSD, VDS, CoA w/w/o VSD/PDA, Cardiomegaly)
  - Anal or rectal atresia
  - NTDs (excluding anencephaly)
  - Caudal regression (pathognomic)
  - Renal anomalies (Ureteral duplication, agenesis, cystic kidneys)
  - Situs inversus
  - IUGR
  - Single umbilical artery
- Polycythemia
- Delayed organ maturation
  - Pulmonary
  - Hepatic
  - Neurologic
  - Pituitary-thyroid axis
  - Parathyroid
Neonatal complications
- Preterm birth
- Respiratory distress (d/t preterm birth)
- Hypoglycemia (d/t hyperplasia of fetal islet cells)
- Hypocalcemia (d/t magnesium-calcium economy unique to diabetic pregnancy, asphyxia, prematurity and pre-eclampsia)
- Hyperbilirubinemia (d/t prematurity and polycythemia)
- Hypertrophic cardiomyopathy (can progress to CHF, common with macrosomia)
Causes of DKA in Pregnancy
- Hyperemesis gravidarum
- Use of B-sympathomimetic drugs for tocolysis
- Infections
- Use of corticosteroids to induce fetal lung maturity
Preconception Treatment
- Normalize blood glucose before conception and during early pregnancy (using HbA1C. >10% increases the risk for malformations
- Folate 400 ug/day pre-conceptually and during early pregnancy
First-trimester Treatment
- Multiple daily insulin injections
- Adjustment of dietary intake
Second-trimester Treatment
- Serum AFP at 16-20 weeks
- Anatomy scan at 18-20 weeks (to detect NTDs and other abnormalities)
Third-trimester Treatment
- Weekly visits to monitor glucose and evaluate for preeclampsia
- Serial ultrasound q3-4 weeks to evaluate excessive or insufficient growth as well as amniotic fluid
Delivery
- After 37 completed terms
- Measure the lecithin-sphingomyelin ratio at 37 weeks
Indications for C-section in Diabetes
- Macrosomia
- Severe hypertension
- Overt diabetes within B or C white classification or vascular disease
Why shouldn’t you use salbutamol as a tocolytic in diabetes?
- May precipitate DKA
Which tocolytics are preferred in Diabetes
- Magnesium sulfate
- Nifedipine
Why are OGLAs not used in the first trimester?
- Cause fetal hyperinsulinemia
- Increased risk of congenital malformations
Contraceptives in diabetes
- Contraindicated COCs d/t increased risk of thromboembolism, stroke and CAD
- Progestin-only can be used in women without vasculopathy or Hx of CAD
- IUDs are safe to used

Best glucose measurements should be done between 2-6 am. Diabetes tends to be unstable in the first trimester. hPL is produced in large amounts in the late second and third trimesters. It antagonizes insulin effects producing high levels of blood glucose

Capillary Glucose goal

Specimen	Blood glucose (mmol/L)
Fasting	3.3-5.0
Premeal	3.3-5.8
Postprandial 1h	5.5-6.7
0200-0600h	3.3-6.7

Obstetric Treatment
- First visit: BP measurement, EKG, 24-hour urine protein and creatinine, HbA1C, TFTs, Ophthalmologic exam
- 15-20 weeks: Quad screen
- 18-20 weeks: Anatomy scan
- 22-24 weeks: Fetal echo
- 32 weeks: weekly NSTs, BPP
- 32-36 weeks: Sonography to assess fetal growth (IUGR, LGA)
- 37 weeks: Induce delivery if fetal lungs are mature
- 38-39 weeks: Induce delivery without testing FLM
Indications for immediate delivery
- Non-reassuring fetal testing
- Very poor glycemic control
- Worsening or uncontrolled hypertension
- Worsening renal disease
- Poor fetal growth
Intrapartum Treatment
- The physical effort of labour usually reduces insulin requirement
- Start Dextrose and Insulin drip with a target glucose of 5.6 – 6.7 mmol/L.
- Check blood glucose q1-2h and adjust insulin and fluids accordingly
Postpartum Treatment
- Significant decline in insulin requirements (esp. Type 2 diabetes)
Follow-up Treatment
- Resume pre-pregnancy regimens, caution OGLAs in breastfeeding
- 6 weeks postpartum: 24-hour urine creatinine and protein in women with significant renal disease
- 12-14 weeks postpartum: repeat ophthalmologic exam and compare to baseline

Target values

Fasting	3.9 – 5.0 mmol/L
One-hour postprandial	< 7.8 mmol/L
Two-hour postprandial	< 6.7 mmol/L

Type 1 diabetes during pregnancy

T1DM is d//t autoimmune destruction of pancreatic beta cells causing insufficient or absent endogenous insulin secretion. Pt insulin requirement increases as the levels of hPL increase during pregnancy. Diet, exercise, stress, and infection may affect glucose levels.

Rules for insulin dose adjustment
- Establish fasting glucose of 3.9 – 5.0 mmol/L
- Only adjust one dose at a time
- Do not change any dosage by more than 20% in one day
- Wait 24 hours between dose changes to assess response

Type 2 diabetes during pregnancy

T2DM is d/t insulin resistance. Resistance to insulin increases d/t increased hPL as pregnancy progresses. Most pts switch from OGLAs to insulin as the pregnancy progresses and glycemic control worsens.

Gestational Diabetes

Gestational diabetes is a condition of glucose intolerance with onset or first recognition in pregnancy. Universal screening is done at 24-28 weeks (the placenta is big enough at this point to secrete hPL). If a positive 50g 1 hr glucose challenge test is followed by a formal 100g 3hr OGTT. A 75g 2-hour fasting OGTT can be done. Conservative tx is preferred first before medical Tx. More than 50% of women with gestational diabetes develop overt diabetes in 20 years.

Modified white classification of pregnant diabetic women

Risk factors
- Gestational diabetes in a previous pregnancy (13x)
- FHx of gestational diabetes
- Age > 30 yo
- Prior macrosomic (> 4.5 kg), malformed or stillborn infant – possibly a previous undiagnosed gestational diabetes
- Obesity
- Hypertension
- Overweight (3x)
- Asian (2x)
- Native American (2x)
- Pacific islander (2x)
- Hispanics (1-2x)
- Blacks (1-2x)
Rule of 15s
- 15% of women will have a positive 50g 1h screen
- Of these women, 15% will have GDM
- Of these women with GDM, 15% will go on to require insulin
Pathophysiology
- The placenta secretes human placental lactogen (hPL) which reduces insulin (along with estrogen and progesterone)
- Maternal pancreatic beta cell hyperplasia in response to reduced sensitivity causes an increase in maternal insulin
- Results in hyperglycemia → crosses the placenta
Screening testsOne-step 75g
- 75g 2h OGTT: diagnosis made with any exceeding value
  - Fasting > 5.1 mmol/L
  - 1 hour > 10.0 mmol/L
  - 2 hours > 8.5 mmol/L
- Two-step
  - 50g 1h OGTT: positive screen > 7.2 mmol/L → get 100g 3h OGTT
  - 100g-3h OGTT: 2 positive values in a single test = GDM;
  - overt diabetes if fasting glucose is >7.0 mmol/L
When is overt diabetes diagnosed?
- Fasting glucose >7.0 mmol/L
Conservative Treatment
- Lifestyle modification
  - Diet restricted at 2,200 Kcal/day with 200-220g carbohydrates
  - Exercise
- Home glucose monitoring qid (fasting and three post-prandial checks)
  - Fasting < 5 mmol/L
  - Post-prandial < 7.8 mmol/L
Medical Treatment
- Insulin: gold-standard
  - 2/3 intermediate-acting insulin (NPH or Lente) in the morning
  - 1/3 short-acting insulin (Regular) in the evening
- OGLAs
  - Metformin
  - Glyburide
Obstetric Treatment
- 32-36 weeks: weekly NST or BPP
- 34-37 weeks: OB sonography for fetal weight (4500g > C-section)
- Good glycemic control: Scheduled delivery at 39-40 weeks
- Poor glycemic control: Scheduled delivery at 37-39 weeks after amniocentesis confirming FLM
Follow-up Treatment
- Screen mother for overt diabetes at first post-partum visit with either fasting glucose or 75g -2hr OGTT (7x more likely to develop T2DM)
- Screen for T2DM every year
Maternal complications
- Obstetric complications
  - Polyhydramnios
  - Pre-eclampsia
  - Postpartum haemorrhage
  - Increased C-section risk
  - Infections- UTIs, pyelonephritis, asymptomatic bacteriuria
- Diabetic emergencies
  - Hypoglycemia
  - DKA
  - Diabetic coma
Fetal complications
- Macrosomia
- Traumatic delivery
- Shoulder dystocia
- Erb’s palsy
Neonatal complications
- Hypoglycemia
- Hyperbilirubinemia
Childhood complications
- Increasing risk of childhood obesity
- Increased risk of developing T2DM later in life

Positive 70g 2h OGTT

Fasting	> 5.1 mmol/l
1 hr	> 10.0 mmol/L
2 hr	> 8.5 mmol/L

Positive 50g 1h OGTT

1 hour	> 7.2 mmol/L

Positive 100g 3h OGTT

Fasting	> 5.1 mmol/L
1 hr	> 10.0 mmol/L
2 hr	> 8.5 mmol/L
3h	> 7.8 mmol/L

Macrosomia

A patient who has been newly diagnosed with gestational diabetes has been started on 20 IU short-term soluble insulin q8h. For long-term treatment, she has to be given long-acting insulin. How will you convert the short-acting insulin into long-acting insulin?

Total dose in 24 hours = 20 X 3 = 60 IU
2/3 of 60 IU = 40 IU of Lente insulin in 24 hours
- 2/3 of 40 IU = 26 IU of Lente insulin given in the morning
- 1/3 of 40 IU = 14 IU of Lente given in the evening
1/3 of 60 IU = 20 IU of regular insulin in 24 hours