Diabetes in Pregnancy
Kirstin Woo, MD
Palo Alto Foundation Medical Group
May 5, 2009
Outline
 Physiologic
changes in pregnancy
– Organ systems affected
– Metabolic changes in pregnancy
 Diabetes
in pregnancy
– Clinical implications
– Epidemiology/Types
– Screening and Diagnosis
– Management
– Future directions
Physiologic changes in pregnancy
 Cardiovascular
system
 Respiratory system
 Gastrointestinal system
 Urinary system
 Endocrine system
 Genital Tract
 Skin
Physiologic changes in pregnancy:
Cardiovascular
Sodium and water retention
 Reduced systemic blood pressure (mean
105/60 mmHg in 2nd trimester)
 Increased cardiac output (30-50% rise)

– Increased blood volume (total body water
increases 40%)
– Reduced systemic vascular resistance
(vasodilitation PLUS high flow, low-resistance
circuit of the uteroplacental circulation)
– Increased maternal heart rate (up 15-20
beats/min)
Physiologic changes in pregnancy:
Respiratory

Mechanical changes
– Diaphragm rises 4 cm
– Less negative intrathoracic pressure
– No impairments in diaphragmatic or thoracic
muscle motion
– Lung compliance remains unaffected

Physiologic changes
–
–
–
–
Oxygen consumption increases 15-20 %
50% of this increase is required by the uterus
Progesterone directly stimulates breathing
70% of women experience dyspnea (increased
desire to breathe)
Physiologic changes in pregnancy:
Gastrointestinal

Mechanical
– Pressure from growing uterus on stomach 
reflux/heartburn
– Pressure from growing uterus on lower portion
of colon and rectum  constipation

Physiologic
– Relaxation of sphincter muscle between
esophagus and stomach
– Progesterone (a smooth muscle relaxant)
causes decreased GI motility and delayed
gastric emptying
Normal glucose metabolism



Glucose enters
bloodstream from food
source
Insulin aids in storage of
glucose as fuel for cells
Insulin resistance is
defined as insensitivity
of cells to insulin,
therefore resulting in
increased levels of
insulin and glucose in
the bloodstream
Metabolic changes in pregnancy
 Caloric
requirement for a pregnant
woman is 300 kcal higher than the
non-pregnant woman’s basal needs
 Placental hormones affect glucose
and lipid metabolism to ensure that
fetus has ample supply of nutrients
Metabolic changes in pregnancy
 Lipid
metabolism:
– Increased lipolysis (preferential use of
fat for fuel, in order to preserve
glucose and protein)
 Glucose
metabolism:
– Decreased insulin sensitivity
– Increased insulin resistance
Metabolic changes in pregnancy
 Increased
insulin resistance
– Due to hormones secreted by the
placenta that are “diabetogenic”:
 Growth
hormone
 Human placental lactogen
 Progesterone
 Corticotropin releasing hormone
– Transient maternal hyperglycemia
occurs after meals because of increased
insulin resistance
Metabolic changes in pregnancy
Relative baseline hypoglycemia
– Proliferation of pancreatic beta cells
(insulin-secreting cells) leads to
increased insulin secretion
 Insulin
levels are higher than in pregnant
than nonpregnant women in fasting and
postprandial states
– Hypoglycemia between meals and at
night because of continuous fetal
draw
 Blood
glucose levels are 10-20% lower
Metabolic changes in pregnancy
 Lipid
metabolism
– Increased serum triglyceride (300%)
and cholesterol (50%) levels
– Spares glucose for fetus, since lipids do
not cross the placenta
– Provides building blocks for increased
steroid hormone synthesis
Outline
 Physiologic
changes in pregnancy
– Organ systems affected
– Metabolic changes in pregnancy
 Diabetes
in pregnancy
– Clinical implications
– Epidemiology/Types
– Screening and Diagnosis
– Management
– Future directions
Diabetes in Pregnancy:
Clinical Implications

Obstetric complications:
– Increased incidence of miscarriage
– Congenital malformations
 Incidence
4X higher than in general population
 Most significant remaining cause of fetal death is
congenital malformation
– Association with hypertensive disorders of
pregnancy
 Gestational
hypertension
 Preeclampsia
Diabetes in Pregnancy:
Clinical implications
Shoulder dystocia
Fetal macrosomia
Diabetes in Pregnancy:
Clinical Implications
 Obstetric
complications (cont’d.):
– Preterm delivery
– Intrauterine fetal demise
– Traumatic delivery (e.g., shoulder
dystocia)
– Operative vaginal delivery


vacuum-assisted
forceps-assisted
Diabetes in Pregnancy:
Clinical Implications

Fetal macrosomia
– Disproportionate amount of adipose tissue concentrated
around shoulders and chest


Respiratory distress syndrome
Neonatal metabolic abnormalities:
–
–
–
–


Hypoglycemia
Hyperbilirubinemia/jaundice
Organomegaly
Polycythemia
Perinatal mortality
Long term predisposition to childhood obesity and
metabolic syndrome
Outline
 Physiologic
changes in pregnancy
– Organ systems affected
– Metabolic changes in pregnancy
 Diabetes
in pregnancy
– Clinical implications
– Epidemiology/Types
– Screening and Diagnosis
– Management
– Future directions
Diabetes in Pregnancy:
Epidemiology


Preexisting diabetes complicates
~1 % of pregnancies in US (>8 million
women)
154,000 (4%) of all pregnancies are
affected by diabetes
– 135,000 (88%) due to GDM
– 12,000 (8%) due to Type 2 DM
–
7,000 (4%) due to Type 1 DM
Diabetes in Pregnancy:
Epidemiology
Geographic disparities
exist in the state of
California with the
highest rates of GDM
reported in the counties
of Alameda, Amador,
Colusa, Glenn,
Monterey, Santa Clara
and Yolo
Diabetes in Pregnancy: Classification
Criterion
White Classification
gestational diabetes, insulin not required
A1
gestational diabetes, insulin required
A2
age of onset >= 20 years (maturity onset diabetes)
B1
duration < 10 years, no vascular lesions
B2
age of onset 10-19 years of age
C1
duration 10-19 years, no vascular lesions
C2
age of onset < 10 years of age
D1
duration >= 20 years
D2
benign retinopathy
D3
calcified arteries of legs
D4
calcified arteries of pelvis (no longer sought)
E
nephropathy
F
many failures
G
cardiopathy
H
proliferating retinopathy
R
renal transplant
T
Diabetes in Pregnancy: Types

Gestational Diabetes Mellitus (GDM)
– Type A1: abnormal oral glucose tolerance test (OGTT)
but normal blood glucose levels during fasting and 1-2
hours after meals; diet modification is sufficient to
control glucose levels
– Type A2: abnormal OGTT compounded by abnormal
glucose levels during fasting and/or after meals;
additional therapy with insulin or other medications is
required

Pregestational Diabetes Mellitus
– Type 1: autoimmune process that destroys pancreatic b
cells
– Type 2 (“lifestyle diabetes”): acquired insulin resistance
related to obesity
Pregestational Diabetes:
Types 1 and 2
Gestational Diabetes (GDM)




Definition:
Insulin resistance/
glucose intolerance first
diagnosed during
pregnancy
Prevalence: 1-14% of
all pregnancies
Indicates predisposition
to later development of
Type 2 Diabetes
Chance of recurrence in
future pregnancies:
30-84%
GDM: Risk factors
 Maternal
age >25 years
 Body mass index >25 kg/m2
 Race/Ethnicity
– Latina
– Native American
– South or East Asian, Pacific Island ancestry
 Personal/Family
history of DM
 History of macrosomia
Gestational Diabetes (GDM)
Outline
 Physiologic
changes in pregnancy
– Organ systems affected
– Metabolic changes in pregnancy
 Diabetes
in pregnancy
– Clinical implications
– Epidemiology/Types
– Screening and Diagnosis
– Management
– Future directions
GDM: Screening

Screening test
– 50 gm 1-hour glucose
challenge test (GCT)

Screening thresholds
– 130mg/dL: 90% sensitivity
(23% screen positive)
– 140mg/dL: 80% sensitivity
(14% screen positive)

If patient screens
positive, she goes on to
take a 3-hour glucose
tolerance test (GTT)
GDM: Diagnosis


Fasting blood glucose >126mg/dL or
random blood glucose >200mg/dL
100 gm 3-hour glucose tolerance test
(GTT) with 2 or more abnormal values
Carpenter and
Coustan
National Diabetes
and Data Group
Fasting
95 mg/dL
105 mg/dL
1 hour
180 mg/dL
190 mg/dL
2 hour
155 mg/dL
165 mg/dL
3 hour
140 mg/dL
145 mg/dL
Outline
 Physiologic
changes in pregnancy
– Organ systems affected
– Metabolic changes in pregnancy
 Diabetes
in pregnancy
– Clinical implications
– Epidemiology/Types
– Screening and Diagnosis
– Management
– Future directions
Management:
Glycemic control
 Significant
benefit of insulin therapy
–Prior to insulin use, perinatal
mortality was 65%
–After introduction of insulin
therapy, perinatal mortality
declined to 5%
Management:
Glycemic control

Glycosylated Hemoglobin A1C (Hgb A1C)
level should be less than or equal to 6%
– Levels between 5 and 6% are associated with
fetal malformation rates comparable to those
observed in normal pregnancies (2-3%)
– Goal of normal or near-normal glycosylated
hemoglobin (Hgb A1C) level for at least 3
months prior to conception

Hgb A1C concentration near 10% is
associated with fetal anomaly rate of 2025%
Management:
Overview
Nutrition therapy
 Home self glucose monitoring
 Medical therapy if glycemic control
not achieved with diet/exercise

– Subcutaneous insulin
– Oral hypoglycemic agents (Glyburide,
Metformin)

Antenatal monitoring
Management:
Glycemic Control
Blood glucose goals during pregnancy
– Fasting < 95mg/dL
– 1-hr postprandial < 130-140mg/dL
– 2-hr postprandial am < 120mg/dL
– 2 am < 120mg/dL
 Nocturnal glucose level should not go below
60 mg/dL
 Abnormal postprandial glucose
measurements are more predictive of
adverse outcomes than preprandial
measurements

Management:
Nutrition

Caloric requirements:
– Normal body weight - 30-35 kcal/kg/day
– Distributed 10-20% at breakfast, 20-30% at
lunch, 30-40% at dinner, up to 30% for snacks
(to avoid hypoglycemia)

Caloric composition:
– 40-50% from complex, high-fiber
carbohydrates
– 20% from protein
– 30-40% from primarily unsaturated fats
Management:
Subcutaneous Insulin Therapy
 Insulin
requirements increase
rapidly, especially from 28 to 32
weeks of gestation
– 1st trimester: 0.7-0.8 U/kg/d
– 2nd trimester: 0.8-1 U/kg/d
– 3rd trimester: 0.9-1.2 U/kg/d
Management:
Subcutaneous Insulin Therapy
“Regular” insulin = Humalog, Novalog
Management:
Oral Hypoglycemic Agents

Glitazones (Avandia, Actos)
– Sensitize muscle and fat cells to accept insulin more
readily
– Decrease insulin resistance

Sulfonylureas
– Augment insulin release
– 1st generation

Concentrated in the neonate  hypoglycemia
– 2nd generation (Glyburide)


Low transplacental transfer
Biguanide (Metformin, aka Glucophage)
– Increases insulin sensitivity
– Crosses placenta
Management Summary:
Pregestational Diabetes
 Referral
to perinatologist and/or
endocrinologist
 Multidisciplinary approach
– Regular visits with nutritionist
– Hgb A1C every trimester
– Fetal Echocardiogram
– Level II ultrasound
– Opthamologist
– Baseline kidney and liver function tests
Management Summary:
Pregestational Diabetes

Optimize glycemic control – frequent
insulin dose adjustments
– Type 1: often have insulin pump
– Type 2: subcutaneous insulin
Fetal monitoring starting at 28-32 weeks,
depending on glycemic control
 Ultrasound to assess growth at 36 weeks
 Delivery at 38-39 weeks

Management Summary:
GDM
 Begin
with diet / walk after each meal
 If borderline/mild elevations, consider
metformin (start at 500 mg daily)
– Counsel about increased PTD rates
– Unlikely pre-existing DM
 If
elevations start out moderate to
severe or metformin fails, proceed to
subcutaneous insulin therapy
– NPH (long acting)
– Humalog/Novalog (short acting)
Management Intrapartum
Attention to labor pattern, as
cephalopelvic disproportion may indicate
fetal macrosomia
 Careful consideration before performing
operative vaginal delivery
 Hourly blood glucose monitoring during
active labor, with insulin drip if necessary
 Notify pediatrics if patient has poorly
controlled blood sugars antepartum or
intrapartum

Management Postpartum
For patients with pregestational diabetes,
halve dose of insulin and continue to
check blood glucose in immediate
postpartum period
 For GDM patients who required insulin
therapy (GDMA2), check fasting and
postprandial blood sugars and treat with
insulin as necessary
 For GDM patients who were diet controlled
(GDMA1), no further monitoring nor
therapy is necessary immediately
postpartum

Management Postpartum
 For
all GDM patients, perform 75
gram 2-hour OGTT at 6 week
postpartum visit to rule out
pregestational diabetes
 Most
common recommendation is for
primary care physician to repeat
2-hour OGTT every three years
Diabetes in Pregnancy:
Future directions
ACOG recommendations on oral
hypoglycemic agents will be updated as
more safety and efficacy data become
available
 Further development of programs for
patient and provider education

– Example: California Diabetes and Pregnancy
Program (CDAPP) consultants develop, update
and disseminate Sweet Success: Guidelines for
Care which provides standards of practice for
diabetes and pregnancy
References






ACOG practice bulletin. Gestational Diabetes.
Obstet Gynecol 2001;93:525-34
ADA position statement. Standards of Medical
Care in Diabetes. Diabetes Care 2006;29:S4-42
Crowther CA et al. N Engl J Med 2005;352:247786
Casey BM et al. Obstet Gynecol 1997;90:867-73
Yang X et al. Diabetes Care 2002;9:1619-24
UpToDate.com
Thanks to Dr. Bertha Chen and Dr. Aaron Caughey
for sharing their slides