When Hyperglycemia Strikes Pregnancy: Criteria for Diagnosis

WHEN HYPERGLYCEMIA
STRIKES PREGNANCY:
CRITERIA FOR DIAGNOSIS

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

Tuesday, November 8, 11

UNITE for Diabetes
CPG on screening &
International diagnosis of GDM
Association of Diabetes
Hyperglycemia in Pregnancy Study
Adverse Pregnancy Groups (IADPSG)
Outcomes (HAPO)


Hyperglycemia Adverse
Pregnancy Outcomes
HAPO


HAPO NEJM 2008; 358:1991-2002
Cord blood serum
BW>90th %ile C-peptide >90 %ile
75-g OGTT
24-32 wks
AOG

23,316
pregnant
15 centers
9 countries

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

BW>90th %ile

1h PG
1.46
(95%CI 1.39,1.53)

Fasting
1.38
OR for (95%CI 1.32,1.44)
2h PG
adverse 1.38
pregnancy (95%CI 1.32,1.44)

outcomes

http://www.ﬂickr.com/photos/mikewade/3267336862/


HAPO NEJM 2008; 358:1991-2002

Cord blood serum
C-peptide >90 %ile

1h PG
1.46
(95%CI 1.38,1.54)

Fasting
1.55
OR for (95%CI 1.47,1.64)
2h PG
adverse 1.37

outcomes

http://www.ﬂickr.com/photos/clairity/1385780317/


HAPO NEJM 2008; 358:1991-2002

Primary CS

1h PG
1.10
(95%CI 1.06,1.15)

Fasting
1.11
OR for (95%CI 1.06,1.15)
2h PG
adverse 1.08

outcomes

http://www.ﬂickr.com/photos/j2dread/4501366303/


HAPO NEJM 2008; 358:1991-2002

Neonatal hypoglycemia

1h PG
1.13
(95%CI 1.03,1.26)

Fasting
1.08
OR for (95%CI 0.98,1.19)
2h PG
adverse 1.10

outcomes

http://www.ﬂickr.com/photos/tessawatson/379265818/


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


Macrosomia
C-section

Hypoglycemia

C-peptide

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


International Association
of Diabetes in Pregnancy
Study Groups
IADPSG


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)



Use of IADPSG criteria

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

More women will be diagnosed with GDM
17.8% of pregnant women
Ryan EA. Diabetologia 2011; 54:480-6


Using HAPO data
+ 1,702 women with GDM
of 23,316 pregnancies

Nurses, dietitians &
physicians
Glucose monitoring
Therapy of diabetes



Diagnosis of GDM identiﬁes
women at risk of type 2 diabetes

IADPSG criteria may
overestimate
high rates of
diabetes in women
with GDM history


X 140 cases of LGA
X 21 cases of shoulder dystocia
X 16 cases of birth injury

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


X 140 cases of LGA
X 21 cases of shoulder dystocia
X 16 cases of birth injury

Modest
outcomes?

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


78% of LGA born to
FBS undiagnosed women
92 mg/dL
1h
180 mg/dL

2h
X
153 mg/dL
BW>90th %ile



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;

icular glucose category; the category incorporating the mean glucose level. This is
r the glucose range. also true for the 1 and 2 h post-load challenge (ESM
roup examined the role Fig. 3). It is also noteworthy that at category 5 (equivalent
Majority of women IADPSG cut-off criteria, accepting that some cases in
mary outcomes [4]. This to the had Most cases of LGA occur
l 1) for many oflevels category 5 will lie abovenormal maternal
glucose the < Cat. 3 in these cut-offs within category 5)
smoking, sex etc.), and women below these cut-offs who had LGA represented
(mean glucose level) glycemia
sted for fasting plasma 78% of all women giving birth to LGA.

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

☐ Participants
infant of birthweight >90th (see text for details). The relationship for maternal fasting glucose
■ Participants with LGA infants
nce group BMI <22.6 kg/m2
ies from HAPO (diamonds;
categories is also shown (black diamonds). b Number of participants
in each category of glucose in HAPO (white bars), with number of
HAPO
lucose [2]). a The BMI c Number of participants in
mothers with LGA infants (black bars).Ryan EA. Diabetologia 2011; 54:480-6
cles) or model 2 (triangles) each category of glucose who had LGA infants

Proposed IADPSG diagnostic criteria are based
on LGA, cord-C peptide and fetal adiposity.

Treatment
reduces
perinatal
ACHOIS morbidity
Landon et al
Crowther et al.
NEJM 2009;
NEJM 2005;
361:1339-48.
352:2477-86.


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.


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


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/


HAPO data collected
at 24-28 wks AOG

Fasting glucose
5.1 mmol/L
at 7 wks AOG
= GDM



IADPSG
ACOG recommends
against IADPSG consensus
1. All pregnant women should be
screened for GDM by patient
history, clinical risk factors or a
50-g, 1-hour loading test to
determine blood glucose levels.

ACOG Committee on Obstetric Practice. Screening & Diagnosis of
http://www.sxc.hu/photo/358002 Gestational Diabetes Mellitus. Obstetrics & Gynecology 2011; 118(3):751-3


IADPSG
ACOG recommends
against IADPSG consensus
2. The diagnosis of GDM can be
made based on the result of the
100-g, 3h OGTT.
Carpenter & Coustan or NDDG criteria



ACOG recommends
IADPSG against IADPSG
consensus
3. Diagnosis of GDM based on
the 1-step screening and
diagnosis test outlined in the
IADPSG guidelines is not
recommended at this time
because there is no evidence that
diagnosis using these criteria leads to
clinically signiﬁcant improvement in
maternal or newborn outcomes, and it
would lead to a signiﬁcant increase in
healthcare costs.



UNITE for Diabetes CPG
on screening &
diagnosis of GDM


6.1 Should universal screening for diabetes
be done among pregnant women?

Recommendation:
All pregnant women should be screened for
gestational diabetes (Level 2, Grade B).


6.2 For pregnant women, when should
screening be done?

Recommendations:
1. All pregnant women should be evaluated at the
ﬁrst prenatal visit for risk factors for diabetes
(Level 4, Grade C).


Risk Factors for
Gestational Diabetes
Prior history of GDM (OR 23.6 [95%CI 11.6, 48.0])3
Glucosuria (OR 9.04 [95%CI 2.6, 63.7]2; PPV 50% 4)
Family history of diabetes (OR 7.1 [95%CI 5.6, 8.9]1; OR 2.74
[95%CI 1.47, 5.11]3)
First-degree relative with type 2 diabetes (PPV 6.7%)4
First-degree relative with type 1 diabetes (PPV 15%)4
Prior macrosomic baby (OR 5.59 [95%CI 2.68, 11.7])3
Age >25 years old (OR 1.9 [95%CI 1.3, 2.7]1; OR 3.37 [95%CI
1.45, 7.85]3)
1 Davey RX, Hamblin PS. Selective versus universal screening for gestational diabetes mellitus:
an evaluation of predictive risk factors. Medical Journal of Australia 2001;174(3):118–21.

! ! 2 Schytte T, Jorgensen LG, Brandslund I, et al. The clinical impact of screening for gestational
diabetes. Clinical Chemistry and Laboratory Medicine 2004;42(9):1036–42.
3 Ostlund I, Hanson U. Occurrence of gestational diabetes mellitus and the value of different screening indicators
for the oral glucose tolerance test. Acta Obstetricia et Gynecologica Scandinavica 2003;82(2):103–8.
4 Grifﬁn ME, Coffey M, Johnson H, et al. Universal vs. risk factor-based screening for gestational diabetes
mellitus: detection rates, gestation at diagnosis and outcome. Diabetic Medicine 2000;17(1):26–32.


Risk Factors for
Gestational Diabetes
Diagnosis of polycystic ovary syndrome
(OR 2.89 [95%CI 1.68, 4.98])5
Overweight or obese before pregnancy
(BMI >27 kg/m2 OR 2.3 [95%CI 1.6, 3.3]1; BMI>30 kg/m2
OR 2.65 [95%CI 1.36, 5.14]3
Macrosomia in current pregnancy (PPV 40% 4)
Polyhydramnios in current pregancy (PPV 40% 4)
Intake of drugs affecting carbohydrate metabolism

1 Davey RX, Hamblin PS. Selective versus universal screening for gestational diabetes mellitus:
an evaluation of predictive risk factors. Medical Journal of Australia 2001;174(3):118–21.
3 Ostlund I, Hanson U. Occurrence of gestational diabetes mellitus and the value of different screening indicators
for the oral glucose tolerance test. Acta Obstetricia et Gynecologica Scandinavica 2003;82(2):103–8.

4 Grifﬁn ME, Coffey M, Johnson H, et al. Universal vs. risk factor-based screening for gestational diabetes
mellitus: detection rates, gestation at diagnosis and outcome. Diabetic Medicine 2000;17(1):26–32.
5 Toulis KA, Goulis DG, Kolibiankis EM, Venetis CA, et al. Risk of gestational diabetes mellitus in women with
polycystic ovary syndrome: a systematic review and a meta-analysis. Fertil Steril 2009;92(2):667–77.


screening be done?

Recommendations:
2. High-risk women should be tested at the
soonest possible time (Level 3, Grade B).


screening be done?

Recommendations:
3. Routine testing for gestational diabetes is
recommended at 24-28 weeks age of gestation
for women with no risk factors (Level 3, Grade B).


screening be done?

Recommendations:
4. Testing for gestational diabetes should still be
carried out in women at risk, even beyond 24 to
28 weeks age of gestation (Level 3, Grade C).


6.3 Which tests should be used to screen pregnant
women for gestational diabetes?

Recommendation:
An oral glucose tolerance test (OGTT), preferably
the 75-g OGTT, should be used to screen for
gestational diabetes (Level 3, Grade B).


6.4 What criteria will be used to interpret
the 75-g OGTT?

Recommendation:

The criteria put forth by the International
Association of Diabetes & Pregnancy Study Groups
(IADPSG) will be used to interpret the 75-g OGTT
(Level 3, Grade B).

International Association of Diabetes and Pregnancy Study Groups Consensus Panel. IADPSG Recommendations on
the Diagnosis and Classiﬁcation of Hyperglycemia in Pregnancy. Diabetes Care 2010; 33(3):676-82.


UNITE for Diabetes
CPG on screening &
International
diagnosis of GDM
Association of Diabetes
in Pregnancy Study
Hyperglycemia
Groups (IADPSG)
Adverse Pregnancy
Outcomes (HAPO)


Thank You!
http://www.endocrine-witch.net

You are all invited to the
19th UPCM Grand Scientiﬁc Symposium
Training the Clinical Eye:
Making the Essential Visible
Hyatt Hotel Manila
Jan 27-28, 2012
19thgss@gmail.com


When Hyperglycemia Strikes Pregnancy: Criteria for Diagnosis

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When Hyperglycemia Strikes Pregnancy: Criteria for Diagnosis