Transcript Gestational Diabetes Dr Ravi Singh

Gestational Diabetes
Ravi Singh
Baker IDI Heart and Diabetes Institute
THE OBJECTIVE OF CARE IN A DIABETIC PREGNANCY
IS TO ACHIEVE PREGNANCY OUTCOMES THAT
APPROXIMATE TO THOSE IN WOMEN WITHOUT
DIABETES
(Maresh 2001)
IDEAL OPPORTUNITY TO IDENTIFY A GROUP AT HIGH
RISK OF DEVELOPING TYPE 2 DIABETES
(Catalano 2000, McElduff 2002)
GESTATIONAL DIABETES (GDM)
CARBOHYDRATE INTOLERANCE OF
VARIABLE SEVERITY WITH ONSET OR
FIRST RECOGNITION DURING PREGNANCY
Type 1
PRE-PREGNANCY DIABETES
Type 2
Incidence and Prevalence
Depends on population studied and diagnostic criteria
8% Melbourne, Vic
4.4% NSW
>2.5 Indigenous SA
Beisher 1996
Anna 2008
Ishak 2003
UK
n=11203 attending ante-natal clinic
4% Europid
1.5% African
7.3% Asian
4.4% Indian
1.4% Mixed race
Dornhurst 1992
Diagnostic Criteria
ADIPS
75gm OGTT
Fasting: ≥5.5 mmol/l
2 hour: ≥8.0 mmol/l
ADA
Fasting: ≥5.3 mmol/l
2 hour: ≥8.6 mmol/l
WHO
Fasting: ≥7.0 mmol/l
2 hour: ≥7.8 mmol/l
24-28 weeks
n=670
ADIPS 18.1%
ADA 6.1%
WHO 12.1%
Sharazian 2008
Complications
Fetal
•LGA
•Macrosomia
•Shoulder Dystocia
•RDS
•Cardiomyopathy
•Jaundice
•Polycythaemia
•↓Glucose/calcium
•Malformations
•Death
Future:
•Diabetes
•Obesity
Maternal
•PIH
•PET
•Polyhydramnios
•Nephropathy
•Hypertension
•Death
Future:
•T2DM (40% Diet, 70% Insulin)
Treatment
Diet/HBGM/exercise etc
Insulin
Oral agents......
Nicholson 2009:
Glibenclamide
Metformin
Meta analysis Oral agents (G/M) v Insulin
4 RCTs n=1229 and 5 Observational studies n=831
Birth weights/congenital malformation/Hypoglycemia
Treatment
Langer 2000
LGA
Macrosomia
Lung
Hypos
Fetal
anomalies
Mat Glucose
Glibenclamide v Insulin
Glibenclamide
12%
7%
8%
9%
2%
Insulin
13%
4%
6%
6%
2%
No difference
n=400
Treatment
Metformin in GDM (MiG Study) Rowan 2008
2002-6 Aust-NZ n=751 GDM (n=363 on Metformin)
GDM= F <5.3mmol/l and 2/3: 1hr >10,
2hr >8.6, 3hr >7.8mmol/l
Randomised, open treatment
Insulin v Metformin ± Insulin
Primary composite
endpoints
Secondary composite
endpoints
Neonatal hypoglycemia, RDS,
Phototherapy, Birth Trauma, Prematurity,
5 minute Apgar score <7
Maternal glycemic control, neonatal
anthropomorphic measurements,
maternal hypertensive complications,
post prandial glucose tolerance,
acceptability/tolerability of treatment
Treatment- MiG Study
Non inferiority study
Primary composite endpoint occurred in:
32% Metformin and 32.2% Insulin
RR 1.0 (95% CI 0.90-1.10)
Limitations:
•Open label design
•Lack of blinding
•Use of superiority design
•Use of composite endpoints of very different
clinical parameters
•Lack of follow up of offspring
Metformin v Insulin Case Control study Balani 2009
Meformin 500mg BD
n= 100 Metformin, n=27 Insulin
Weight gain
PIH
PET
IOL
C-section
Perinatal loss
Prematurity
Jaundice
NICU
Macrosomia
Insulin
2.72±0.4
7%
2%
24%
52%
0%
10%
30%
19%
25%
Metformin
0.94±0.3
6%
9%
26%
48%
0%
0%
8%
6%
14%
p value
<0.001
0.9
0.06
0.87
0.67
<0.01
<0.01
<0.01
0.07
Outcomes-Pre-gestational diabetes
Jenson 2009 Pre conceptual HbA1c and outcomes
T1DM n=933 Denmark
Outcomes-Pre-gestational diabetes
Dunne 2009 ATLANTIC DIP Study
Irish
n=104 T1DM/T2DM
Outcomes-Pre-gestational diabetes
•Women not well prepared for pregnancy
Only 28% get pre-pregnancy care
Only 43% get pre-pregnancy folic acid
•Women in country areas have worse outcomes
PET
CS
NELCS
Diabetes
14%
43%
25%
NGT
5%
27%
13%
Still brith
25/1000, x5 background rate
Perinatal mortality
25/1000, x3.5 background rate
Malformation
24/1000, x2 background rate
HbA1c during pregnancy
(no difference between city/country)
Mean HbA1c
Overall HbA1c ≤7% in
51% at booking
Booking visit
7.8%
End 1st Trimester
7.4%
End 2nd Trimester
6.2%
End 3rd Trimester
6.6%
Pre-delivery
7.2%
Outcomes-GDM
RCT n=958, mild GDM; EASD/NEJM Landon 2009
24-31 gest
Mild GDM= GCT ≥7.5-11.1mmol/l
+ fasting <5.3mmol/l and 2/3 after 100gm OGTT:
1HR >10.0mmol/l, 2 hr >8.6mmol/l, 3hr >7.8mmol/l
Usual care n=473, treatment grp n=485
Excluded: Prev GDM/steroids/SB/BP/fetal anomaly
N0 difference in primary outcome:
Composite of Still Birth, perinatal death and neonatal
complications (hyperbilirubinemia, hypoglycemia, hyperinsulinemia or birth trauma)
Usual care
Treatment
Birth wt
3408gm
3302gm
Neonatal mass
464gm
427gm
LGA
14.5%
7.1%
Macrosomia
14.3%
5.9%
Shoulder dystocia
4.0%
1.5%
C-Section
33.8%
26.9%
PET/PIH
13.6%
8.6%
All
p=0.01
Continuous relationship between maternal glucose: Birth wt/cord c-peptide levels
Borderline GDM (BGDM) and outcomes
GDM v NGT
South Australia Ju 2008
BGDM: GDM= GCT ≥7.8mmol/l + NGT= F <5.5, 2hr <7.8mmol/l
Estimate ~6.6% (16,500) have borderline GDM in Aust
BGDM
NGT
RR
95% CI
Mean age
Older 1.3
yrs
Obese
27.1%
14.4%
1.92
1.41-2.03
Adverse
maternal
outcome
12.9%
8.1%
1.59
1.0-2.52
0.05
PIH
17.9%
11.8%
1.51
1.03-2.20
0.03
C-section
FDIU
17.1%
10.5%
1.63
1.1-2.41
0.03
0.1-0.7
0.01
Postnatal
stay
0.3-2.2
p value
Mean difference 0.4 days
0.01
0.0001
Borderline GDM (BGDM) and outcomes
For infants:
BGDM
NGT
RR
95% CI
P value
Pre term
10.7%
6.4%
1.68
1.0-2.8
0.05
Macroso
mia
4.3%
1.7%
2.53
1.066.03
0.04
NICU
6.5%
3.0%
2.18
0.94.36
0.03
ACHOIS
Australian carbohydrate
intolerance study in pregnant women
Crowther 2005
n= 1000 GDM routine v intervention
Mean age 26, European background, BMI 26
ACHOIS GDM= GCT ≥7.8mmol/l
75gm OGTT 24-34 gest
F >7.8mmol/l
2hr ≥7.8-11.0 mmol/l
ADIPS GDM= 75gm OGTT 24-28 gest
F >5.5mmol/l
2hr >7.8mmol/l
HAPO
Hyperglycemia (short of diabetes) and adverse
pregnancy outcomes (perinatal)
Metzger 2008
Multinational/cultural/ethnic study over 7 years,
n= 25,505 Prospective, observational, blinded
75gm OGTT at 24-32 gest
Blinded IF F <5.8mmol/l
2hr <11.1 mmol/l
Primary outcomes
•Birth wt >90th centile for GA
•Primary c-section
•Neonatal hypoglycemia
•Cord blood c-peptide >90th centile
Secondary outcomes
•Delivery <37 weeks gest
•Shoulder dystocia/injury
•NICU admission
•Hyperbilirubinemia
•PET
Adjusted for: field centre, maternal BMI, BP, Ht, parity, baby gender,
ethnic grp
HAPO
Calculated OR for adverse pregnancy outcomes associated with an
increase in:
Increase Fasting glucose of 1 SD (0.4mmol/l)
Increase 1 Hour glucose of 1 SD (1.7mmol/l)
Increase 2 hour glucose of 1 SD (1.3mmol/l)
Glucose categoreis defined from 1-7:
Glucose
categories
Fasting Glucose 1 Hour glucose
(mmol/l)
(mmol/l)
2 Hour glucose
(mmol/l)
1
<4.2
<5.8
<5.0
2
4.2-4.4
5.9-7.3
5.1-6.0
3
4.5-4.9
7.4-8.6
6.1-6.9
4
4.8-4.9
8.7-9.5
7.0-7.7
5
5.0-5.2
9.6-10.7
7.8-8.7
6
5.3-5.5
10.8-11.7
8.8-9.8
7
>5.6
>11.8
>9.9
Frequency of primary outcomes across the glucose categories
(adjusted)
Hyperglycemia and Adverse Pregnancy
Outcome (HAPO) Study: Associations
with Neonatal Anthropometrics 2009
Abstract
Objective: To examine associations of neonatal adiposity with maternal glucose levels
and cord serum C-peptide in a multicenter multinational study, the Hyperglycemia and
Adverse Pregnancy Outcome (HAPO) Study, thereby assessing the Pederson
hypothesis linking maternal glycemia and fetal hyperinsulinemia to neonatal adiposity.
Research Design and Methods: Eligible pregnant women underwent a standard 75 gm
OGTT between 24 and 32 weeks gestation (as close to 28 weeks as possible). Neonatal
anthropometrics and cord serum C-peptide were measured. Associations of maternal
glucose and cord serum C-peptide with neonatal adiposity (sum of skinfolds > 90th
percentile or percent body fat > 90th percentile) were assessed using multiple logistic
regression analyses, with adjustment for potential confounders, including maternal age,
parity, BMI, mean arterial pressure, height, gestational age at delivery, and the baby's
gender.
Results: Among 23,316 HAPO study participants with glucose levels blinded to
caregivers, cord serum C-peptide results were available for 19,885 babies and skin fold
measurements for 19,389. For measures of neonatal adiposity there were strong
statistically significant gradients across increasing levels of maternal glucose and cord
serum C-peptide, which persisted after adjustment for potential confounders. In fully
adjusted continuous variable models, odds ratios ranged from 1.35 to 1.44 for the two
measures of adiposity for fasting, 1-hour, and 2-hour plasma glucose higher by one
standard deviation.
Conclusions: These findings confirm the link between maternal glucose and neonatal
adiposity, and suggest that the relationship is mediated by fetal insulin production and
that the Pedersen hypothesis describes a basic biologic relationship influencing fetal
growth.
Conclusion
•GDM is important
•Treatment does make a difference
•Oral agents can be considered
•Shortly to find out:
•Universal screening method
• Time to test
• Threshold values
•Pre-pregnancy and Post partum management needed