1. DDiiaabbeetteess aanndd pprreeggnnaannccyy
Nguyen Thy Khue, MD, PhD

2. DDiiaabbeetteess iinn pprreeggnnaannccyy
 2-20% of all pregnancies
 Pregestational diabetes (approximately
20%)
 Gestational diabetes (GDM - approximately
80%)

3. WWhhaatt iiss ggeessttaattiioonnaall ddiiaabbeetteess
 ”Any degree of glucose intolerance
with onset or first recognition during
pregnancy” (1980-2010)
 GDM vs ”overt diabetes” detected in
pregnancy (2010)
Metzger et al. Summary and recommendations of the Fourth International Workshop-Conference Diabetes Care 1998
International Association for Diabetes in Pregnancy Study Groups. Recommendations on the diagnosis and classification of
hyperglycaemia during pregnancy Diabetes Care 2010

4. PPaatthhoopphhyyssiioollooggyy ooff GGDDMM
Increased Insulin resistance
Increased insulin secretion
Adequate in the first trimester
Inadequate as gestation progress
Inadequate insulin secretion
HYPERGLYCEMIA
Buchanan et al. GDM: risks and management during and after
pregnancy Nat Rev Endocrinol 2012 Nov;8(11):639-49

5. CCoommppaarriissoonn wwiitthh ttyyppee 22 ddiiaabbeetteess
Increased Insulin resistance
Inadequate Insulin secretion
Stumvoll et al. Type 2 diabetes:principles of pathogenesis and therapy Lancet 2005 365(9467):1333-46

6. RRiisskk ffaaccttoorr ooff GGDDMM
 Obesity or excessive gestational weight gain
 Ethnicity associated with higher type 2
diabetes risk
 Current glucocorticoid use
 Hypertension
 Family history of diabetes
 Glycosuria

7. RRiisskk ffaaccttoorr ooff GGDDMM
 Previous poor obstetric outcome
 Previous GDM
 Polycystic Ovarian Syndrome
 Age 25 or over
 Previous macrosomic baby
 Maternal macrosomia or low birth weight

8. Pedersen Hypothesis
PPlalacceenntata
MMaateternrnaal lh hyyppeergrglylycceemmiaia
FFeetatal lh hyyppeergrglylycceemmiaia
Fetal hyperglycemia
Fetal hyperglycemia
and hyperinsulinemia
FFeetatal lh hyyppeerirninssuulilnineemmiaia and hyperinsulinemia
1. Congenital anomalies
1. Congenital anomalies
(peri-conceptional)
(peri-conceptional)
2. Decreased early
growth (0-20 weeks
2. Decreased early
growth (0-20 weeks
gestation)
gestation)
3. Hyperinsulinemia
(>20 weeks gestation)
3. Hyperinsulinemia
(>20 weeks gestation)
1. Neonatal
1. Neonatal
hypoglycemia (0-7 days
hypoglycemia (0-7 days
postnatal)
postnatal)
2. Surfactant deficiency
2. Surfactant deficiency
(neonatal)
(neonatal)
3. Immature liver
3. Immature liver
metabolism (neonatal)
metabolism (neonatal)
aa. .J Jaauunnddicicee
1. Fetal macrosomia
(>20 weeks gestation)
1. Fetal macrosomia
(>20 weeks gestation)
a. Birth asphyxia
b. Cardiomyopathy
c. TTN
a. Birth asphyxia
b. Cardiomyopathy
c. TTN
2. Fetal hypoxia
2. Fetal hypoxia
(>30 weeks gestation)
(>30 weeks gestation)
aa. .P Poolylyccyyththeemmiaia
cc. .I rIoronn a abbnnoormrmaaliltiiteiess
b. Stroke,
b. Stroke,
Poor
RVT Poor
RVT
neurodevelopmental
neurodevelopmental
outcome
outcome

9. Perinatal ccoonnsseeqquueenncceess ooff GGDDMM
Outcome Odds ratio
Macrosomia 2.66
Large for gestational age 3.28
Caesarean section 1.88
Shoulder dystocia 4.07
Hypoglycemia 10.38
Hyperbilirubinemia 3.87
Erythrocytosis 10.88
Respiratory complications 4.40
Stillbirth 1.91
Langer et al. Gestational diabetes: the consequences of not treating Am J Obst Gynecol 2005 23(3):196-8

10. MMaatteerrnnaall ccoonnsseeqquueenncceess ooff GGDDMM
 Type 2 diabetes
 Relative risk 7.7 (up to 60% at 16 years)
 Metabolic syndrome
 3-fold increase (38.4 vs. 13.4%)at 9.8 years
 Cardiovascular disease
 Hazard ratio 1.66 at 12.3 years

11. Impact of GDM on Pregnancy Outcomes
The Hyperglycemia and Adverse Pregnancy
Outcomes (HAPO) Study
Rationale:
•Overt diabetes increases the risk of adverse
pregnancy outcomes.
•What level of glucose intolerance during pregnancy,
short of diabetes, is associated with the risk of adverse
outcomes?
Metzger BE, et al. HAPO Study Cooperative Research Group. N Eng J Med 2008;358:1991-2002.

12. HAPO Protocol
75 g OGTT 24-32 weeks
Fasting, 1 & 2 hr venous plasma
N = 25,505
Unblinded at field centre if
OGTT fasting >105 &/or 2 hr >200
or random glucose ≥160 ~36 wks
Or <45 mg/dL
1,443 (5.7%) incomplete
23,316
Standard care for field centre
Cord glucose & C-peptide
Neonatal glucose: 1-2 hr of age
Anthropometrics by 72 hr:
746 (2.9%) unblinded
Length, head circ, weight, skin folds x3
for treatment
Metzger BE, et al. HAPO Study Cooperative Research Group. N Eng J Med 2008;358:1991-2002.

13. HHyyppeerrggllyycceemmiiaa aanndd AAddvveerrssee PPrreeggnnaannccyy
OOuuttccoommeess ((HHAAPPOO)) ssttuuddyy
• N=23,316 women
• 75g OGTT 24-32 weeks gestation
– Fasting glucose ≤ 5.8 mmol/L
– 2-hour glucose ≤ 11.1 mmol/L
• Composite of 4 perinatal outcomes
HAPO Study Group. Hyperglycemia and Adverse Pregnancy Outcomes NEJM 2008 358:1991–2002

14. HHyyppeerrggllyycceemmiiaa aanndd AAddvveerrssee PPrreeggnnaannccyy
OOuuttccoommeess ((HHAAPPOO)) ssttuuddyy
HAPO Study Group. Hyperglycemia and Adverse Pregnancy Outcomes NEJM 2008 358:1991–2002

15. HHyyppeerrggllyycceemmiiaa aanndd AAddvveerrssee PPrreeggnnaannccyy
OOuuttccoommeess ((HHAAPPOO)) ssttuuddyy
Outcome
Odds Ratio
Fasting
glucose
Odds Ratio
1-hour
glucose
Odds
Ratio 2-
hour
glucose
Birth weight > 90th
centile
1.38* 1.46* 1.38*
Cord C-peptide >90th
centile
1.55* 1.46* 1.37*
Primary Caesarean
Section
1.11* 1.10* 1.08*
Clinical neonatal
hypoglycaemia
1.08 1.13* 1.10
*statistically significant
HAPO Study Group. Hyperglycemia and Adverse Pregnancy Outcomes NEJM 2008 358:1991–2002

16. IADPSG Consensus CCoonnffeerreennccee 22001100
GDM* Overt
diabetes
Fasting plasma glucose –
mg/dl (mmol/l)
≥92
(5.1)
≥126
(7.0)
1-hour glucose- mg/dl
(mmol/L)
≥180
(10.0)
2-hour glucose- mg/dl
(mmol/L)
≥153
(8.5)
≥200
(11.1)
*only one abnormal value required
International Association for Diabetes in Pregnancy Study Groups. Recommendations on the diagnosis and classification of
hyperglycaemia during pregnancy Diabetes Care 2010 33(3):676-82

17. GGDDMM pprreevvaalleennccee IIAADDPPSSGG ccrriitteerriiaa
Data from Sacks et al Frequency of Gestational Diabetes Mellitus at Collaborating Centers Based on IADPSG Consensus Panel–
Recommended Criteria Diabetes Care 2012 35:526–528

18. Outcomes of GDM Pregnancies in Urban
Vietnam
• Most available data on the pregnancy outcomes of GDM
are from high-income countries.
• 2,772 Vietnamese women in Ho Chi Minh City were
monitored through routine prenatal care.
– 75 g OGTT between 24-32 weeks.
– GDM diagnosis using either 2010 ADA criteria
(2 positive results from OGTT), or IADPSG criteria
(1 positive result from OGTT)
No GDM
Borderline GDM
(IADPSG +ve;
2010 ADA -ve)
GDM
(2010 ADA +ve)
Prevalence 79.6% 14.5% 5.9%
BMI 20.45 kg/m2 21.10 kg/m2 21.81 kg/m2
Hirst JE, et al. PLoS Med 2012;9(7):e1001272.

19. Neonatal Outcomes of GDM Pregnancies in
Urban Vietnam
No GDM
Borderline GDM
(IADPSG +ve;
2010 ADA -ve)
GDM
(2010 ADA +ve)
Gestation at birth (weeks) 1.48% 1.67% 1.70%
Preterm delivery (<37
weeks) 6.55% 9.59%* 14.02%*
>90th percentile for
gestational age 11.76% 16.06% 18.90%
<10th percentile for
gestational age 8.04% 6.99% 6.10%
Clinical neonatal
hypoglycemia 0.70% 2.33%* 14.02%*
Jaundice requiring
phototherapy 3.02% 4.15% 4.27%
Intensive neonatal care 4.0% 4.40% 5.49%
Perinatal death 0.4% 0.8% 0%
Hirst JE, et al. PLoS Med 2012;9(7):e1001272.

20. Maternal Outcomes of GDM Pregnancies in
Urban Vietnam
No GDM
Borderline GDM
(IADPSG +ve;
2010 ADA -ve)
GDM
(2010 ADA +ve)
Preeclampsia 1.63% 2.59% 0.61%
Primary caesarean section 33.46% 31.35% 40.85%
Induction of labour 2.84% 3.88% 7.64%*
Severe perineal trauma 2.81% 3.06% 2.78%
Postpartum hemorrhage
(>500 mL) 4.32% 4.15% 3.66%
Hirst JE, et al. PLoS Med 2012;9(7):e1001272.

21. International
Recommendations on
Screening for GDM

22. GDM: Clinical Risk Assessment
Risk category Clinical characteristics
High risk Obesity
Family history
Personal history IGT
Prior macrosomic infant
Current glycosuria
Average risk Neither low or high risk
Low risk <25 yrs
Low-risk ethnicity
No family history
Normal pre-pregnancy weight and
pregnancy weight gain
No personal history of abnormal glucose levels
No prior poor obstetrical outcomes
ADA. Therapy for Diabetes Mellitus and Related Disorders. 5th Edition. 2009.

23. When to screen for GDM?
For women at high risk:
• Screen for undiagnosed T2DM at first
prenatal visit.
• Diabetes detected during this visit
constitutes a diagnosis of overt, not
gestational, diabetes.
ADA. Standards of Medical Care in Diabetes. Diabetes Care 2014;37(suppl 1):S14-S80.

24. When to screen for GDM?
For women at average risk:
• Screen for GDM at 24-28 weeks gestation.
• Due to increasing global rates of diabetes,
ADA recommends:
– 2-hr 75 g OGTT.
– Consider a single abnormal value as diagnostic.
ADA. Standards of Medical Care in Diabetes. Diabetes Care 2014;37(suppl 1):S14-S80.

25. Screening and Diagnosis of GDM
Criteria Diagnosis
ADA (2014) GDM defined when any of the following values are exceeded:
Fasting ≥92 mg/dL (5.1 mmol/L)
1-h ≥180 mg/dL (10.0 mmol/L)
2-h ≥153 mg/dL (8.5 mmol/L)
IADPSG GDM defined as at least one value meeting the threshold:
Fasting plasma glucose ≥5.1 mmol/L
1-h plasma glucose ≥10.0 mmol/L
2-h plasma glucose ≥8.5 mmol/L
WHO GDM defined as diabetes or impaired glucose tolerance.
Diabetes defined as at least one value meeting the threshold:
•Fasting plasma glucose ≥7.0 mmol/L
•2-h plasma glucose ≥11.1 mmol/L
Impaired glucose tolerance defined as:
•Fasting plasma glucose <7.0 mmol/L
•2-h plasma glucose ≥7.9 mmol/L
ADIPS GDM defined as at least one value meeting the threshold:
Fasting plasma glucose ≥5.5 mmol/L
2-h plasma glucose ≥8.0 mmol/L

26. Screening for GDM (ADA 2014)
• Perform a 75 g OGTT, with plasma
glucose measurement fasting, and at 1
and 2 hrs, at 24-28 weeks gestation in
women not previously diagnosed with
overt diabetes.
• Perform OGTT in the morning after an
overnight fast of at least 8 hrs.
ADA. Standards of Medical Care in Diabetes. Diabetes Care 2014;37(suppl 1):S14-S80.

27. GDM Diagnosis
• Plasma glucose values:
– Fasting ≥92 mg/dL
– 1 hr ≥180 mg/dL
– 2 hr ≥153 mg/dL
• Women found to meet criteria at first
prenatal visit should receive a diagnosis of
overt diabetes.
ADA. Standards of Medical Care in Diabetes. Diabetes Care 2014;37(suppl 1):S14-S80.

28. Selection of a Screening Strategy in
Low-/Middle-Income Countries
• In resource-poor settings, screening must be
optimized to reduce cost.1
• A 2013 study of Vietnamese patients found that:
• Using a risk-threshold of 3%, the ADA 2010 criteria
had a sensitivity of 93% for GDM patients.
• Selective screening of patients results in 27% fewer
glucose tolerance tests than systematic screening.2
• The study authors concluded that the ADA 2010
strategy may be a reasonable approach in
conditions of limited resources.2
1.Gupta Y, Gupta A. Diabetes Care 2013;36(10):e185.
2.Tran TS, et al. Diabetes Care 2013;36(3):618-24.

29. Treatment ooff mmiilldd GGDDMM LLaannddoonn eett aall
Outcome Routine care
(n=510)
Intervention
(n=490)
p value
Hypoglycaemia 15.4% 16.3% 0.75
Perinatal death 0.0% 0.0% N/A
Elevated cord C-peptide 22.8% 17.7% 0.07
Birth trauma 1.3% 0.6% 0.33
Neonatal jaundice 12.9% 9.6% 0.12
Birth weight>4kg 14.3% 5.9% <0.001*
Large for gestational age 14.5% 7.1% <0.001*
*p<0.05
03-12-14 29
Landon et al. A multicentre, randomized trial of treatment for GDM NEJM 2009 361(14):1339-48

30. Treatment ooff mmiilldd GGDDMM LLaannddoonn eett aall
Outcome Routine care
(n=510)
Intervention
(n=490)
p value
Caesarean section 33.8% 26.9% 0.02*
Shoulder dystocia 4.0% 1.5% 0.02*
Preeclampsia 5.5% 2.5% 0.02*
**pp<<00..0055
LLaannddoonn eett aall.. AA mmuullttiicceennttrree,, rraannddoommiizzeedd ttrriiaall ooff ttrreeaattmmeenntt ffoorr GGDDMM NNEEJJMM 22000099 336611((1144))::11333399--4488

31. Glycemic Targets During Pregnancy:
AACE & ADA Guidelines1,2
Glucose
Increment Patients with GDM
Patients with
Preexisting T1DM or
T2DM
Preprandial,
premeal
≤95 mg/dL (5.3 mmol/L) Premeal, bedtime, and
overnight glucose:
60-99 mg/dL
(3.4-5.5 mmol/L)
Postprandial,
post-meal
1-hour post-meal: ≤140 mg/dL
(7.8 mmol/L) or
2-hour post-meal: ≤120 mg/dL
(6.7 mmol/L)
Peak postprandial
glucose 100-129 mg/dL
(5.5-7.1 mmol/L)
A1C A1C ≤6.0%
1. AACE. Endocr Pract. 2011;17(2):1-53.
2. ADA. Diabetes Care. 2013;36(suppl 1):S11-66.

32. Glycemic Targets During Pregnancy:
Expert Recommendations
Some experts recommend more stringent goals
(in particular, for patients on insulin therapy)
to prevent maternal and fetal complications1,2
Glucose
Increment
Patients With Gestational
Diabetes Mellitus (GDM)1
Patients With
Preexisting T1DM or
T2DM1,2
Preprandial,
premeal
≤90 mg/dL (5.0 mmol/L)1,2
Postprandial,
post-meal
1-hour post-meal: ≤120 mg/dL (6.7 mmol/L)1,2
A1C A1C <5.0%3 A1C <6.0%4
1. LeRoith D, et. al. Endocrinol Metab Clin N Am. 2011;40(1): xii-919.
2. Castorino K et al. Curr Diab Rep, 2012;12:53-59.
3. L. Jovanovic; personal communication.
4. AACE. Endocr Pract. 2011;17(2):1-53.

33. Glucose Monitoring in GDM:
Self-Monitoring of Blood Glucose
• Self-monitoring of blood glucose (SMBG) is the
cornerstone of diabetes management in
gestational diabetes mellitus (GDM)1
• ADA guidelines for pregnant patients requiring
insulin:
– SMBG ≥3 times daily
– More frequent SMBG may be required, including:2
• Morning fasting
• Premeal (breakfast, lunch, and dinner)
• 1-hour postprandial (breakfast, lunch, and dinner)
• Before bed3
1. Jovanovic L, et al. Diabetes Care. 2011;34(1):53-54. 2. ADA. Diabetes Care. 2013;36(suppl 1):S11-
S66. 3. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30. .

34. Glucose Monitoring in GDM: HbA1C
• Provides valuable supplementary information for glycemic
control
• To safely achieve target glucose levels, combine A1C
with frequent self-monitoring of blood glucose (SMBG)1,2
• Recent research suggests weekly HbA1C during
pregnancy:1
– SMBG alone can miss certain high glucose values
– SMBG + HbA1C = more complete data for glucose control
– Clinicians can further optimize treatment decisions with weekly
HbA1C
1. Jovanovic L, et al. Diabetes Care. 2011;34(1):53-54.
2. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.

35. Diet/Exercise
 Traditionally carbohydrate restriction to
approximately 40% of total intake
 Limited evidence
 Appropriate weight gain
 Maximum 9kg if obese
 Exercise plus diet lower glucose /HbA1c
 High level of exercise in studies
 Evidence for perinatal outcome measurements lacking

36. Carbohydrate Source Exchange
1 Exchange : 175 calorie, 4 g protein, 40 g CHO

37. MMaannaaggeemmeenntt ooff GGDDMM
• Medical nutrition therapy (MNT) and lifestyle
changes can effectively manage 80% to 90%
of mild GDM cases1,2
• As pregnancy progresses, glucose intolerance
typically worsens; patients may ultimately
require insulin therapy1,3
1. Chitayat, L, et al. Diabetes Technology & Therapeutics. 2009;11:S105-111. 2. ADA. Diabetes Care. 2013;36(suppl 1):S11-66.
3. ADA. Diabetes Care. 2004;27(suppl 1):S88-90. 4.

38. Insulin
 Most experience with human insulin
 Regular insulin, NPH
 Insulin aspart and lispro appear safe and
effective
 Insulin detemir appears safe and effective
 Insulin glargine is likely to be safe, but less
evidence to date

39. Gestational Diabetes Mellitus (GDM):
Initiation of Insulin
Glucose Levels for Insulin Initiation in GDM1
Fasting plasma glucose ≤105 mg/dL (5.8 mmol/L)
1-hour postprandial plasma glucose ≤155 mg/dL (8.6
mmol/L)
2-hour postprandial plasma glucose ≤130 mg/dL (7.2
mmol/L)
1. ADA. Diabetes Care. 2004;27(suppl 1):S88-90.

40. Choice of Insulin
Insulin Options Shown to Be Safe During Pregnancy1
Name Type Onset Peak
Effect Duration Recommended
Dosing Interval
Aspart Rapid-acting
(bolus) 15 min 60 min 2 hrs Start of each meal
Lispro Rapid-acting
(bolus) 15 min 60 min 2 hrs Start of each meal
Regular
insulin
Intermediate-acting
60 min 2-4 hrs 6 hrs 60-90 minutes
before meal
NPH Intermediate-acting
(basal) 2 hrs 4-6 hrs 8 hrs Every 8 hours
Detemir Long-acting
(basal) 2 hrs n/a 12 hrs Every 12 hours
1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.
2. Kitzmiller JL, et al. Diabetes Care. 2008;31(5):1060-79.

41. Insulin Use During Pregnancy
1. Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):269-80. 2. AACE. Endocr Pract. 2011;17(2):1-53.
3. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30. 4. ADA. Diabetes Care. 2004;27(suppl 1):S88-90.

42. Women with GDM History
80-90% of women with mild GDM can be
managed by lifestyle changes alone
ADA. Standards of Medical Care in Diabetes. Diabetes Care 2014;37(suppl 1):S14-S80.

43. Summary
• It is important to screen pregnant patients at
risk of GDM to achieve an early diagnosis.
• Diagnostic criteria (based on HAPO findings)
aim to decrease the risk of hyperglycemia in
both mothers and infants.

44. Summary (cont.)
• Women at high risk should be screened for TD2M at
their first prenatal visit.
• Women at average risk should be screened for GDM
at 24-28 weeks gestation.
• 2 hr 75 g OGTT should be used with a single abnormal
value qualifying as diagnostic.
• 80-90% of mild GDM cases could be managed by
lifestyle changes and medical nutrition therapy