Jill Mauldin, MD

Maternal Fetal Medicine

Medical University of SC

Objectives
1.
2.
3.
4.
5.

Definition and Management of GDM

Average BS during Non-DM and DM pregnancies
Adverse pregnancy outcomes related to elevated BS
Long term effects to the infants of DM pregnancies
Obstacles to BS control

Gestational Diabetes
Glucose intolerance first diagnosed during pregnancy
Non-diagnosed Type 2 DM
Incidence 4-7%
Ultimately 12-15%
Gestational DM
45% risks of GDM with next pregnancy
65% risk of developing Type 2 DM

Gestational DM: Screening and Diagnosis

24-28 weeks gestation

Plasma glucose
(mg/dL)

Diagnosis is made when

> 2 values are abnormal

1 hr

< 135

Fasting

< 95

1 hr

< 180

2 hr

< 155

3 hr

< 140

Gestational DM Maternal and Fetal Risks

Short-term

Long-term

Macrosomia

30-40%

Diabetes

50%

Obesity

NN Hypoglycemia

65%

Respiratory Distress

Hypertension

Cesarean Delivery

Metabolic Syndrome

Insulin Secretion
Insulin
Resistance

Insulin
Secretion

Pregnancy

Insulin
Resistance

Insulin
Secretion

GDM

Pancreatic reserves

by 2/3

Gestational DM Type 2 DM
Diabetes

IFG

Overweight

Obese
GDM

IGT

Insulin resistance

UKPDS: -cell function

United Kingdom Perspective Diabetes Study

4209 newly diagnosed diabetic women

-cell function
At diagnosis: 51%

After 6 yrs:

28%
After 12 yrs: negligible

Typical T2 DM Treatment
Oral Monotherapy

Oral Combined

Oral Combined
w/Long acting Insulin

UKPDS. Lancet. 1998

Treatment modalities of DM

Sulfonylureas

Insulin Secretion
Insulin Sensitivity
Hepatic Glucose
Production
Requirement: Residual cell function

Oral Hypoglycemics
Trade Name

Sulfonylureas

Glipizide
Glyburide

Mechanism

Peak

Half-life

Side Effects

Dose

Increase
insulin
secretion
Glucotrol

Diabeta /
Micronase
Glimepiride
Amaryl

4 hr

10 hr

Not studied / used during pregnancy

Hypoglycemia
(10-40%)

2.5mg
20mg

GDM: Glyburide vs. Insulin

GDM: Glyburide vs. Insulin

11 - 33 weeks gestation
Singleton gestation
Gestational diabetes
Fasting glucose > 95 < 140
Randomized to glyburide or insulin management
Pre- and Post-prandial blood sugars
Goal:

fasting 60-90 mg/dl

preprandial 80-95 mg/dl

postprandial < 120 mg/dl
Langer. NEJM. 2000

GDM: Glyburide vs. Insulin 1 Outcome

o

404

201
Glyburide

162 (82%)

203
Insulin

Good BS Control

170 (88%)

8 (4%)
Failed

Langer. NEJM, 2000

GDM: Glyburide vs. Insulin 2 Outcomes

o

Langer. NEJM, 2000

GDM: Glyburide vs. Insulin 2 Outcomes

o

Maternal Blood Sugar control

Cord Insulin Values
Neonatal outcomes

LGA infants 4-7%

Respiratory complications 2-3%
Hypoglycemia 6-9%
NICU admissions 6-7%
Fetal anomalies 2-3%
Langer. NEJM, 2000

Glyburide
Very little placental transfer
Benefits mother
Indirectly benefits fetus
Endorsed
ACOG, 2001
N American Diabetes in Pregnancy Study Group, 2002
5th International Workshop on GDM, 2005

Insulin Analogues
Rapid Acting: Insulin Lispro, Aspart
Recombinant DNA technology

~ 30mg/dl decrease of post-prandial BG

HbA1c decreases by additional 0.5%
Hypoglycemia decreases by 30-50%

Insulin Analogs
Lispro
vs. Regular Human Insulin
Similar anti-insulin antibody

levels
Lower BS results
Fewer hypoglycemic episodes
None detected in umbilical
cord blood
Improved glucose
control/maternal satisfaction

Glycemic Profiles Non-Diabetic Pregnancies

Continuous Glucose Monitoring

Glucose sensing electrode
Impregnated with glucose oxidase
Measurement every 10 sec

Average reported every 5 min

288 values/day

Glycemic Profiles Non-Diabetic Pregnancies

57 patients
12 months
Inclusion criteria
Singleton pregnancy
No chronic disease
No B-mimetics, steroids

Screened at 24-28 weeks

< 130 considered non-diabetic

Excluded if GDM ultimately diagnosed

BMI > 27.3 obese
Yogev et al. AJOG 2004

Glycemic Profiles Non-Diabetic Pregnancies

Blood Glucose
Mean

83.7

Fasting

75

Pre-meal

78.2

Post-meal peak

110.1

Post-meal peak time

70.5 min

Mean at night

68.3

< 140

Yogev et al. AJOG 2004

Glycemic Profiles Non-Diabetic Pregnancies

120
100
80
Blood
60
Glucose
40

N=42

N=15

< 27.3

> 27.3

20

ave BS
Fasting
Peak
Time of peak

0
BMI
Yogev et al. AJOG 2004

Glycemic Profiles Diabetic Pregnancies

Glycemic Profiles Diabetic Pregnancies

65 patients
26 diet controlled GDM
19 insulin-requiring GDM
20 Type 1 DM

GDM diagnosed by Carpenter/Coustan criteria

Insulin started if fasting > 105, 2h PP > 120

72 hr Continuous Glucose Monitoring and self

finger sticks
NPH/Regular insulin
Ben-Haroush et al. AJOG, 2004

Glycemic Profiles Diabetic Pregnancies

Diet
GDM

Insulin
GDM

Type 1
DM

P value

N=19

N-26

N=20

Mean

94

110

116

< 0.001

Pre-meal

84

101

103

0.005

Post-meal peak

131

148

182

< 0.001

Peak Time

82

85

93

0.423

Ben-Haroush et al. AJOG, 2004

Glycemic Profiles Diabetic Pregnancies

NonDiabetic
N=57

Diet
GDM

Insulin
GDM

Type 1
DM

N=19

N-26

N=20

Mean

83.7

94

110

116

Pre-meal

78.2

84

101

103

110.1

131

148

182

70.5

82

85

93

Post-meal peak
Peak Time

Ben-Haroush et al. AJOG, 2004

Yogev et al. AJOG 2004

Glycemic Profiles Diabetic and Non-DM Pregnancies

200
180
160
140
Blood 120
100
Glucose
80
60
40
20
0

ave BS
Fasting
Peak
Time of peak

<
>
Diet Ins
27.3 27.3 GDM GDM
BMI

T1
DM

Yogev et al. AJOG 2004

Ben-Haroush et al. AJOG, 2004

Gestational DM
Is it really so bad to have slightly elevated BS?
Is it necessary or important to treat the BS of a patient

with GDM?
200
180
160
140
Blood 120
100
Glucose
80
60
40
20
0

ave BS
Fasting
Peak
Time of peak

<
27.3

>
Diet Ins
27.3 GDM GDM

T1
DM

Treatment of GDM

Treatment of GDM
100 (20%)
insulin
490
Intervention Group
1000
Enrolled/Randomized
16-30 weeks

506 Live Births

Fasting <99, 2hr < 126

510
Routine Care

17 (3%)
insulin

524 Live Births

Crowther, NEJM, 2005

Treatment of GDM

Primary Outcomes

Crowther, NEJM, 2005

Treatment of GDM

Secondary Outcomes

Crowther, NEJM, 2005

Hyperglycemia and Pregnancy

HAPO Trial Hyperglycemia and Adverse Pregnancy Outcome

Is mild glucose intolerance associated with adverse
perinatal outcomes and if so, what is the threshold that
identifies risk?
Measured
Outcomes

Design

International
Prospective
25,000 pts
24-32 wks
75g glucola
Unblinded if
signif GDM:
fasting > 105,
2hr > 200

Stillbirth
Hypoglycemia
Hyperbili
Hyperinsulin
Birth trauma
C/S rate
Macrosomia

Results
As fasting BS
increases,
there is a
linearly
increased risk
of macrosomia

HAPO Trial Hyperglycemia and Adverse Pregnancy Outcome

International Workshop
GDM Diagnosis and Classification, June 2008
Hyperglycemia is associated with:
Increased macrosomia
Increased cord-blood C-peptide
Diagnostic cut-offs will most likely be lowered
As a result, 12-15% of the population will have GDM.

Intrauterine Exposure to Elevated BS

Diabetes, 2000

Intrauterine Exposure

P = 0.003

52 Families

Dabelea et al. Diabetes, 2000

Intrauterine Exposure to Elevated BS

Intrauterine Exposure
Children aged 6-11yrs

Prevalence of Metabolic Syndrome: Obesity, HTN, Inc TG, Dec HDL

Boney et al. Pediatrics, 2005

Intrauterine Exposure
N = 83
P = 0.56

N = 92
P = 0.004

Boney et al. Pediatrics, 2005

Obstacles to GDM Control

Short time period to effect treatment
Education
Diet management
Medications
Multiple visits required
Location of patient from their health care provider

Summary
GDM: Glucose intolerance first diagnosed during

pregnancy
Management: Diet, Glyburide, Insulin

Average Blood sugars

70-100s

80-130s

110-180s

Summary
Maternal hyperglycemia is associated with:
LGA, Macrosomia
Death, Shoulder dystocia, Bone Fracture, Nerve palsy
Intrauterine exposure to hyperglycemia is associated

with a lifetime risk of:

BMI
Metabolic syndrome, obesity, DM

70-100s

80-130s

110-180s

 To waste several weeks by not treating GDM is time

allowing the fetus to become macrosomic.

Lois Jovanovic, MD
International Workshop Conference on Gestational Diabetes
Diagnosis - and Classification, June 2008

Glycemic Profiles

Glycemic Profiles Non-Diabetic Pregnancies

Yogev et al. AJOG 2004