Gestational Diabetes: An Update

GESTATIONAL DIABETES:
AN UPDATE

Iris Thiele Isip Tan MD, MSc, FPCP, FPSEM
Clinical Associate Professor, UP College of Medicine
Section of Endocrinology, Diabetes & Metabolism
Department of Medicine, Philippine General Hospital

Friday, November 18, 11

1964 1982 2008 2010
1972 1996 2003 2006 2011

MD
1st Son #1 Son #2
Here I am!
birthday
http://www.ﬂickr.com/photos/yogma/3961135108/ http://www.sxc.hu/photo/533027


“For at least a generation there has been
a divergence of opinions about GDM.”
Robert G. Moses, MD
New Consensus Criteria for GDM: Problem Solved or a Pandora’s Box
Diabetes Care 2010;33(3):690-1

1964 1982 2008 2010
1972 1996 2003 2006 2011

MD
1st Son #1 Son #2
Here I am!
birthday


“For at least a generation there has been
a divergence of opinions about GDM.”
Robert G. Moses, MD
New Consensus Criteria for GDM: Problem Solved or a Pandora’s Box
Diabetes Care 2010;33(3):690-1

IADPSG
O’Sullivan Carpenter Consensus
& Mahan & Coustan
criteria
HAPO
1964 1982 2008 2010
1972 1996 2003 2006 2011

MD
1st Son #1 Son #2
Here I am!
birthday


International Implications on
Association of Diabetes screening and
in Pregnancy Study diagnosis of GDM
Hyperglycemia Groups (IADPSG)
Adverse Pregnancy
Outcomes (HAPO)


Hyperglycemia Adverse Pregnancy Outcomes

HAPO
NEJM 2008; 358:1991-2002

large
diverse
population 25,505 pregnant
single protocol
15 centers
9 countries
Thailand, Hong Kong, Singapore


75-g OGTT
24-32 weeks

Results
unblinded if
FPG >105 mg/dL
2h PG >200 mg/dL
RPG >160 mg/dL
any PG <45 mg/dL

HAPO
NEJM 2008; 358:1991-2002


HAPO NEJM 2008; 358:1991-2002
Cord blood serum
BW>90th %ile C-peptide >90 %ile

Primary
OUTCOMES

Primary CS Neonatal hypoglycemia
http://www.flickr.com/photos/mikewade/3267336862/ http://www.flickr.com/photos/clairity/1385780317/
http://www.flickr.com/photos/j2dread/4501366303/ http://www.flickr.com/photos/tessawatson/379265818/


OR for adverse pregnancy outcomes

1 level SD
increase

FPG 6.9 mg/dL (0.4 mmol/L)
1 h PG 30.9 mg/dL (1.7 mmol/L)
2 h PG 23.5 mg/dL (1.3 mmol/L)

HAPO NEJM 2008; 358:1991-2002


HAPO NEJM 2008; 358:1991-2002
1h PG
1.46
Fasting (95%CI 2h PG
BW>90th %ile 1.39,1.53)
1.38 1.38
(95%CI (95%CI
1.32,1.44)
OR
1.32,1.44)

Fasting
1.55
(95%CI 1h PG
1.47,1.64)
1.46
(95%CI
1.38,1.54)
2h PG
1.37
Cord blood serum (95%CI
1.30,1.44)
C-peptide >90 %ile http://www.ﬂickr.com/photos/mikewade/3267336862/
http://www.ﬂickr.com/photos/clairity/1385780317/


HAPO NEJM 2008; 358:1991-2002
1h PG
1.10
Fasting (95%CI 2h PG
Primary CS 1.06,1.15)
1.11 1.08
(95%CI (95%CI
1.03,1.12)
OR
1.06,1.15)

Fasting
1.08
(95%CI 1h PG
0.98,1.19)
1.13
(95%CI
1.03,1.26) 2h PG
Neonatal 1.10
hypoglycemia (95%CI
1.00,1.12)
http://www.ﬂickr.com/photos/tessawatson/379265818/
http://www.ﬂickr.com/photos/j2dread/4501366303/


No obvious
threshold
at which risks increased

HAPO NEJM 2008; 358:1991-2002


No obvious
threshold FPG mg/dL
at which risks increased Category
1 <75
2 75-79
3 80-84
4 85-89
5 90-94
6 95-99
7 >100

HAPO NEJM 2008; 358:1991-2002


No obvious
threshold 1h PG mg/dL
1 <105
2 106-132
3 133-155
4 156-171
5 172-193
6 194-211
7 >212

HAPO NEJM 2008; 358:1991-2002


No obvious
threshold 2h PG mg/dL
1 <90
2 91-108
3 109-125
4 126-139
5 140-157
6 158-177
7 >178

HAPO NEJM 2008; 358:1991-2002


LGA
C-section

Hypoglycemia

C-peptide

HAPO NEJM 2008; 358:1991-2002


“Lack of clear thresholds and the fact that
the four primary outcomes are not necessarily
of equal clinical importance make direct
translation of our results into clinical practice
challenging.”

HAPO NEJM 2008; 358:1991-2002


“... the relationship between
maternal glucose levels and fetal
growth and outcome appear to be
a basic biologic phenomenon, and
not a clearly demarcated
disease state ...”

Coustan et al. AJOG 2010; 202(6):654.e1-654.e6


“What is a challenge is to decide how
much increase in risk is the point at which
treatment should be initiated and what is the
hope and expectation for the treatment to
reduce those risks ...”
Metzger B. Endocrine Today 2008


“Secondly, should the associations of glucose
be weighted equally with the primary
outcomes or are some more important than
others?

The third issue is whether all of the glucose
measures are needed to identify increased risk.”
Metzger B. Endocrine Today 2008


International
Association of Diabetes
in Pregnancy Study
Hyperglycemia Groups (IADPSG)
Adverse Pregnancy
Outcomes (HAPO)


IADPSG
encourage and facilitate
research and advance
education
facilitate an international
approach to enhancing the
quality of care for women
with diabetes in pregnancy

http://www.sxc.hu/photo/358002


IADPSG
workshop/conference
June 2008
(220 delegates
approx 40 countries)

consensus development
session (50 delegates)



OR for increased neonatal body
fat, LGA and cord serum C-peptide

Mean
glucose as
reference

Positive Predictive Value
% for >90th %ile
OR Subjects >
Birth
Threshold C-peptide % Body fat
weight
1.75 16.1 16.2 17.5 16.6
2.0 8.8 17.6 19.7 18.8



IADPSG recommendation for diagnosis of GDM
FBS 92 mg/dL
Diagnosis requires only one
1h 180 mg/dL threshold value exceeded

2h 153 mg/dL



FBS 92 mg/dL
Diagnosis requires only one
1h 180 mg/dL threshold value exceeded

2h 153 mg/dL

ADA
FBS 95 mg/dL
1h 180 mg/dL
2h 155 mg/dL



First prenatal visit
Measure FPG, A1c or random
plasma glucose in all or only in high-risk

Overt
Diabetes in
Gestational Order a 75-g
Pregnancy
Diabetes OGTT at 24-28
FPG > 7 mmol/L wks AOG
A1c > 6.5% FPG
Random PG > 5.1-6.9 mmol/L FPG
11.1 mmol/L (92-125 mg/dL) <5.1 mmol/L

IADPSG Consensus Panel. Diabetes Care Mar 2010;33(3):676-82


FBS 92 mg/dL
24-28 wks AOG
1h 180 mg/dL Diagnosis requires only one
threshold value exceeded
2h 153 mg/dL

Overt diabetes
FPG >7.0 mmol/L (126 mg/dL)



Implications on screening
and diagnosis of GDM


Use of IADPSG criteria
More women will be diagnosed with GDM
17.8% of pregnant women in HAPO

http://www.ﬂickr.com/photos/kkoshy/4334413228/

+ 1,702 women with GDM
from 2,448 to 4,150 of 23,316 pregnancies in HAPO
Ryan EA. Diabetologia 2011; 54:480-6


n = 1038

50-g GCT

Morikawa M. Diab Res Clin Pract 2010; 90:339-42.


n = 1038

50-g GCT

+ GCT
>7.8 mmol/L

n = 228



n = 1038

GCT
-
50-g GCT <7.8 mmol/L
n = 810
+ GCT
>7.8 mmol/L

n = 228



n = 1038

GCT
-
n = 810
+ GCT
>7.8 mmol/L

n = 228

75-g OGTT
Japan SOG criteria
FPG>100 mg/dL
1h PG >180 mg/dL
2h PG >150 mg/dL


n = 1038

GCT
-
n = 810
+ GCT
>7.8 mmol/L

n = 228

75-g OGTT OGTT
+
Japan SOG criteria >7.8 mmol/L
FPG>100 mg/dL
n = 25
1h PG >180 mg/dL
2h PG >150 mg/dL


n = 1038

GCT
-
n = 810
+ GCT
OGTT
>7.8 mmol/L -
>7.8 mmol/L
n = 228
n = 203

75-g OGTT OGTT
+
FPG>100 mg/dL
n = 25
1h PG >180 mg/dL
2h PG >150 mg/dL


n = 1038

GCT
-
50-g GCT <7.8 mmol/L IADPSG
+ criteria
n = 810
+ GCT
OGTT
>7.8 mmol/L -
>7.8 mmol/L 43 GDM
n = 228
n = 203

75-g OGTT OGTT
+ 5 overt DM
20 GDM
FPG>100 mg/dL
n = 25
1h PG >180 mg/dL
2h PG >150 mg/dL


n = 1038 Total 68 GDM
172% increase
GCT
-
+ criteria
n = 810
+ GCT
OGTT
>7.8 mmol/L -
>7.8 mmol/L 43 GDM
n = 228
n = 203

75-g OGTT OGTT
+ 5 overt DM
20 GDM
FPG>100 mg/dL
n = 25
1h PG >180 mg/dL
2h PG >150 mg/dL


Impact on workload of changing GDM
diagnostic criteria by lowering fBGL alone
and with increasing 2h BGL (IADPSG)

29% increase
in workload

extra 366 women
diagnosed
ADIPS criteria
fBGL >5.5 mmol/L
2h BGL >8.0 mmol/L
Flack JR et al. Aus NZ J Obstet Gynecol 2010; 50:439-43.


“One approach will be to argue that we
cannot cope with the change in numbers and
that these new criteria should be ignored.”

will leave a signiﬁcant number at risk untreated...



Adjust thresholds for fasting, 1h & 2h BG
levels “to keep the number of women
diagnosed with GDM stable ... an example of
explicit rationing of medical care.”



Stratify risk.

“Those women diagnosed at the lower end
of the ‘new’ diagnostic range may be
expected to be at ‘lower risk’ and if so, their
management ‘may’ be ...‘less stringent’.”



OGTT n = 25
+ 20 GDM
>7.8 mmol/L 5 overt DM
needed insulin
n = 228
OGTT n = 203
75-g OGTT -
>7.8 mmol/L IADPSG criteria
Japan SOG criteria
FPG>100 mg/dL 43 GDM
1h PG >180 mg/dL of which 5
2h PG >150 mg/dL needed insulin

IADPSG “overt diabetes” diagnosis may help
differentiate women who need insulin from
women who do not need insulin.


IADPSG criteria X 140 cases of LGA
X 21 cases of shoulder dystocia
X 16 cases of birth injury
of 23,316 pregnancies
in HAPO cohort

Ryan EA. Diabetologia 2011; 54:480-6 http://www.sxc.hu/photo/249796


IADPSG criteria X 140 cases of LGA
X 21 cases of shoulder dystocia
X 16 cases of birth injury
of 23,316 pregnancies
in HAPO cohort

Modest
outcomes?

Ryan EA. Diabetologia 2011; 54:480-6 http://www.sxc.hu/photo/249796


n = 1038 Total 68 GDM
172% increase
GCT
-
+ criteria
n = 810
+ GCT
OGTT
>7.8 mmol/L -
>7.8 mmol/L 43 GDM
n = 228
n = 203

75-g OGTT OGTT
+ 5 overt DM
20 GDM
FPG>100 mg/dL
n = 25
1h PG >180 mg/dL
2h PG >150 mg/dL
Morikawa M. Diab Res Clin Pract 2010;90: 339-42.


OGTT n = 25
+ 5 overt DM
+ GCT >7.8 mmol/L 20 GDM
n = 228
OGTT n = 203
75-g OGTT -
>7.8 mmol/L 43 GDM
Japan SOG criteria
FPG>100 mg/dL IADPSG criteria
1h PG >180 mg/dL no speciﬁc treatment
2h PG >150 mg/dL for GDM

Morikawa M. Diab Res Clin Pract 2010;90 339-42.


OGTT n = 25
+ 5 overt DM
+ GCT >7.8 mmol/L 20 GDM
n = 228
OGTT n = 203
75-g OGTT -
>7.8 mmol/L 43 GDM
Japan SOG criteria
FPG>100 mg/dL IADPSG criteria
1h PG >180 mg/dL no speciﬁc treatment
2h PG >150 mg/dL for GDM
6 infants >3600 g (14%)
p=0.021 vs non-GDM 3.8% (n=160)
Number Needed to Treat (NNT)
1/(0.14-0.038) = 9.8
Morikawa M. Diab Res Clin Pract 2010;90 339-42.


Nurses, dietitians &
physicians
Glucose monitoring
Therapy of diabetes


Cost-effective strategy based on risk
GDM risk <1%: no screening/treatment strategy
1-4.2%: FPG followed by OGTT
>4.2%: OGTT alone
Round JA et al. Diabetologia 2011; 54:256-63

Nurses, dietitians &
physicians
Glucose monitoring
Therapy of diabetes


RR for developing
gestational diabetes by
ethnicity (adjusted for age, BMI and
parity; white as reference)

UK Data (1992) RR (95%CI)
Black 3.1 (1.8 to 5.5)
South East Asian 7.6 (4.1 to 14.1)
Indian 11.3 (6.8 to 18.8)

Dornhorst A, Paterson CM, Nicholls JSD, et al. High prevalence of gestational
diabetes in women from ethnic minority groups. Diabetic Medicine 1992; 9:820–5.


AFES Study Group on Diabetes
in Pregnancy (ASGODIP)

ASGODIP protocol
1-step (high-risk)
Prevalence (%) 75-g OGTT
Indonesia 16 2h cut-off 140 mg/dL
Malaysia 13 Philippines n/N
Philippines 14 Low risk 35/853
Singapore 10 High risk 136/350
Thailand 13 171/1203
Overall
ASEAN 13 14.2%

Litonjua AD et al. AFES Study Group on Diabetes in Pregnancy:
Preliminary Data on Prevalence. PJIM 1996:34:67-68.


Increased prevalence of GDM using the
IADPSG criteria “can only be justiﬁed if it is
shown convincingly that pregnancy
outcomes are improved.”

Holt RIG et al. Diabete Med 2011; 28:382-5.


Landon et al
NEJM 2009; M
361:1339-48.
O Randomized
Composite of controlled
I stillbirth/ trial
perinatal
P Intervention death and
(n=485)
neonatal
diet CBG insulin
complications
vs hyperbilirubinemia
routine care hypoglycemia
(n=473) hyperinsulinemia
birth trauma

“mild” GDM
24-31 wks AOG
Landon MB et al. A multicenter, randomized trial of treatment
for mild gestational diabetes. NEJM 2009; 361:1339-48.


Composite endpoint
RR 0.87 (95% CI 0.72-1.07), p=0.14
Landon et al
NEJM 2009; M
361:1339-48.
O Randomized
Composite of controlled
I stillbirth/ trial
perinatal
P Intervention death and
(n=485)
neonatal
diet CBG insulin
complications
vs hyperbilirubinemia
routine care hypoglycemia
(n=473) hyperinsulinemia
birth trauma

“mild” GDM
24-31 wks AOG


Composite endpoint
RR 0.87 (95% CI 0.72-1.07), p=0.14
Landon et al
NEJM 2009; M
361:1339-48.
O Randomized
controlled
I trial
P Intervention
(n=485)
diet CBG insulin
vs
routine care
(n=473)

“mild” GDM
24-31 wks AOG


Composite endpoint
RR 0.87 (95% CI 0.72-1.07), p=0.14
Landon et al
NEJM 2009; M
361:1339-48.
O Randomized
LGA infants controlled
I RR 0.49 trial
P Intervention (95%CI 0.32-0.76)
p<0.001
(n=485)
diet CBG insulin BW >4000 g
vs RR 0.41
routine care (95%CI 0.26-0.66)
(n=473) p<0.001

“mild” GDM
24-31 wks AOG


ACHOIS
Crowther et al.
NEJM 2005; M
352:2477-86.
O Randomized
controlled
I Serious trial
perinatal
P Intervention complications
(n=490)
death
diet CBG insulin shoulder dystocia
vs bone fracture
nerve palsy
routine care
(n=510)

GDM
24-28 wks AOG
Crowther CA et al. Effect of Treatment of Gestational Diabetes
Mellitus on Pregnancy Outcomes. NEJM 2005; 352:2477-86.


Any serious perinatal complication
ACHOIS Adj RR 0.33 (95% CI 0.14-0.75), p=0.01
Crowther et al.
NEJM 2005; M
352:2477-86.
O Randomized
controlled
I Serious trial
perinatal
P Intervention complications
(n=490)
death
diet CBG insulin shoulder dystocia
vs bone fracture
nerve palsy
routine care
(n=510)

GDM
24-28 wks AOG
Crowther CA et al. Effect of Treatment of Gestational Diabetes
Mellitus on Pregnancy Outcomes. NEJM 2005; 352:2477-86.


OGTT is poorly reproducible
Diagnosis based on a single
test, on a single abnormal value

Ryan EA. Diabetologia 2011; 54:480-6 http://www.ﬂickr.com/photos/craigoneal/4084388198/


report used an adjustment (Model 1) for many of the
expected confounders (age, alcohol, smoking, sex etc.), and
Greater impact of maternal BMI on
also a model (Model 2) that adjusted for fasting plasma
OR for LGA than maternal glucose
except highest glucose category
a b
8,000

5
● 6,000 Model 1
BMI

Women (n)
4
▲ 4,000 Model 2
BMI
OR

3
2 ◆ Maternal FG
2,000
1
0 0
1 2 3 4 5 6 7 1 2 3
Glucose category
Glucos
<22.6 22.6− 28.5− 33.0− 37.5− 42.0
28.4 32.9 37.4 41.9
BMI category (Kg/m2)

Fig. 1 a Relationship of the OR for an infant of birthweight >90th
Model 1: Adjusted for age, alcohol, smoking, sex, etc. HAPO
Model 2: Adjusted for mean FG and MAP 2
percentile vs the BMI in categories (reference group BMI <22.6 kg/m

[4]) or maternal fasting glucose in categories from HAPO (diamonds;

roup examined the role Fig. 3). It is also noteworthy that at category 5 (equivalent
mary outcomes [4]. This to the IADPSG cut-off criteria, accepting that some cases in
l 1) for many of of women hadwill lie above these cut-offs within category 5)
Majority the category 5 Most cases of LGA occur
smoking, sex etc.),levels women below these in normal maternalrepresented
glucose and < Cat. 3 cut-offs who had LGA
sted for fasting glucose78% of all women giving birth to LGA.
(mean plasma level) glycemia
b c
8,000 700
600
6,000 500
Women (n)

Women (n)
400
4,000
300

2,000 200
100
0 0
1 2 3 4 5 6 7 1 2 3 4 5 6 7
Glucose category Glucose category

78% of LGA born to women
☐ Participants categories is also shown (black diamonds). IADPSG participants
not fulﬁlling b Number of criteria
infant of birthweight >90th (see text for details). The relationship for maternal fasting glucose
2
nce group BMI <22.6 kg/m
ies from HAPO (diamonds; in each category of glucose in HAPO (white bars), with number of
■ Participants with LGA infants
lucose [2]). a The BMI
cles) or model 2 (triangles)
mothers with LGA infants (black bars). c Number of participants in
each category of glucose who had LGA infants
HAPO


Diagnosis of GDM identiﬁes
women at risk of type 2 diabetes

GDM
independent risk
factor for diabetes in
Filipino-Americans
RR 21.65
(95%CI 6.73-69.67)

IADPSG criteria
may overestimate
risk of diabetes
Cuasay et al. Diabetes Care 2001;24(12):2054-8


IADPSG Consensus

Approved by ADA
ACOG did not approve

ACOG Committee on Obstetric Practice. Screening & Diagnosis of
Gestational Diabetes Mellitus. Obstetrics & Gynecology 2011; 118(3):751-3


Philippine Diabetes CPG has partially
adopted the IADPSG consensus by
endorsing the HAPO-derived thresholds for
the 75-g OGTT.


THANK YOU
http://www.endocrine-witch.net
isiptan@gmail.com


Gestational Diabetes: An Update

Recommended

Recommended

More Related Content

More from Iris Thiele Isip-Tan

More from Iris Thiele Isip-Tan (20)

Recently uploaded

Recently uploaded (20)

Gestational Diabetes: An Update