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Updates in Gestational Diabetes
1. Updates in Gestational Diabetes
Iris Thiele Isip Tan MD, MSc, FPCP, FPSEM
Associate Professor 4, UP College of Medicine
Chief, UP Medical Informatics Unit
9 July 2014
Thursday, July 10, 14
3. Implications of
using IADPSG criteria
women serie 2 by asterisco
http://www.freeimages.com/photo/313127
Outline
Tablets
vs insulin
white round pills by dimshilk
http://www.freeimages.com/photo/755944
Lactation
after GDM
Lactation2 by carin
http://www.freeimages.com/photo/161052
Thursday, July 10, 14
4. Implications of
using IADPSG criteria
women serie 2 by asterisco
http://www.freeimages.com/photo/313127
Thursday, July 10, 14
5. Philippine Diabetes CPG has partially
adopted the IADPSG consensus by
endorsing the HAPO-derived thresholds for
the 75-g OGTT.
Thursday, July 10, 14
6. Hyperglycemia Adverse Pregnancy Outcomes
HAPO
25,505 pregnant
15 centers
9 countries
Thailand, Hong Kong, Singapore
NEJM 2008; 358:1991-2002
large
diverse
population
single protocol
Thursday, July 10, 14
7. OR for increased neonatal body
fat, LGA and cord serum C-peptide
Mean
glucose as
reference
Coustan et al. AJOG 2010; 202(6):654.e1-654.e6
OR
%
Subjects >
Threshold
Positive Predictive Value
for >90th %ile
Positive Predictive Value
for >90th %ile
Positive Predictive Value
for >90th %ile
OR
%
Subjects >
Threshold Birth
weight
C-peptide % Body fat
1.75 16.1 16.2 17.5 16.6
2.0 8.8 17.6 19.7 18.8
Thursday, July 10, 14
8. Coustan et al. AJOG 2010; 202(6):654.e1-654.e6
IADPSG recommendation for diagnosis of GDM
FBS 92 mg/dL
1h 180 mg/dL
2h 153 mg/dL
Diagnosis requires only one
threshold value exceeded
Overt diabetes
FPG >7.0 mmol/L (126 mg/dL)
24-28 wks AOG
Thursday, July 10, 14
9. http://www.sxc.hu/photo/358002
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
Gestational Diabetes Mellitus. Obstetrics & Gynecology 2011; 118(3):751-3
Thursday, July 10, 14
10. http://www.sxc.hu/photo/358002
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 Committee on Obstetric Practice. Screening & Diagnosis of
Gestational Diabetes Mellitus. Obstetrics & Gynecology 2011; 118(3):751-3
Thursday, July 10, 14
11. http://www.sxc.hu/photo/358002
IADPSG
ACOG recommends
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.
ACOG Committee on Obstetric Practice. Screening & Diagnosis of
Gestational Diabetes Mellitus. Obstetrics & Gynecology 2011; 118(3):751-3
Thursday, July 10, 14
12. The ACOG... recommends that before
the testing approach and diagnostic criteria
are changed, implications of such
changes should be studied.
“
Thursday, July 10, 14
14. Diabetes Care
35:526-528, 2012
Although the new diagnostic criteria for GDM apply globally,
center-to-center differences occur in GDM frequency
and relative diagnostic importance of
fasting, 1-h and 2-h glucose levels.
“Thursday, July 10, 14
15. Bellflower, CA
Singapore, Singapore
Cleveland, OH
Manchester, UK
Bangkok, Thailand
Chicago, IL
Belfast, UK
Toronto, Canada
Providence, RI
Newcastle, Australia
Hongkong, PRC
Brisbane, Australia
Bridgetown, Barbados
Petah-Tiqva, Israel
Beersheba, Israel
0 750 1500 2250 3000
Normal
GDM
Frequency of GDM by HAPO Center using IADPSG criteria
Sacks DA et al Diabetes Care 2012;35:526-8
25.1%
23%
14.4%
Thursday, July 10, 14
16. HAPO
Bellflower, CA
Singapore, Singapore
Cleveland, OH
Manchester, UK
Bangkok, Thailand
Chicago, IL
Belfast, UK
Toronto, Canada
Providence, RI
Newcastle, Australia
Hongkong, PRC
Brisbane, Australia
Bridgetown, Barbados
Petah-Tiqva, Israel
Beersheba, Israel
0 50 100 150 200
FPG
1h
2h
Percent of GDM women: values above OGTT threshold
Sacks DA et al Diabetes Care 2012;35:526-8
47 65 47
24 76 43
26 62 65
55 33 12
Thursday, July 10, 14
17. HAPO
Bellflower, CA
Singapore, Singapore
Cleveland, OH
Manchester, UK
Bangkok, Thailand
Chicago, IL
Belfast, UK
Toronto, Canada
Providence, RI
Newcastle, Australia
Hongkong, PRC
Brisbane, Australia
Bridgetown, Barbados
Petah-Tiqva, Israel
Beersheba, Israel
0 24 48 72 96 120
FPG
1h
2h
Percent of GDM diagnosed by each glucose measure
Sacks DA et al Diabetes Care 2012;35:526-8
47 39 14
24 64 12
26 45 29
55 33 12
Thursday, July 10, 14
18. Given that there is a continuum of risk,
no criteria will ever be comprehensive.
Given that the criteria are based on a
consensus, there will always be
an opportunity for divergent opinions.
Moses RG. Diabetes Care 2012;35:461-2
“
Thursday, July 10, 14
19. Diabetes Care
35:1894-6, 2012
Israeli HAPO participants n=3,345
1
3
2
Adverse outcomes compared
IADPSG criteria
IADPSG criteria with risk stratification
Screening with BMI or fasting plasma glucose
Thursday, July 10, 14
20. Adopting IADPSG increases GDM diagnosis by ~50%
1/3 of IADPSG(+) women at low risk for adverse outcomes
Kalter-Leibovici et al. Diabetes Care 2012;35:1894-6.
Thursday, July 10, 14
21. Association of GDM diagnosed using IADPSG & POGS
75-g OGTT cut-off values with adverse perinatal outcomes in PGH
Urbanozo H & Isip Tan, IT
In press, JAFES
Sept-Dec 2013
PGH OB Charity ward report
885 deliveries
GDM
n=104
not GDM
n=132
EXCLUDED
100g OGTT done n=88
only FBS done n=52
No OGTT done n=365
OGTT results not available n=48
Chart not available n=52
Multiple gestation n=16
Maternal age <18 y.o. n=20
Pregestational DM n=8
Chart review
75-g OGTT
Thursday, July 10, 14
22. Association of GDM diagnosed using IADPSG & POGS
75-g OGTT cut-off values with adverse perinatal outcomes in PGH
Urbanozo H & Isip Tan, IT
In press, JAFES
GDM: increased risk of primary CS (OR 1.79 [1.02–3.16], p=0.041) and
NICU admission (OR 2.66 [1.3–5.44], p=0.007)
FBS >92 mg/dL: increased risk of LGA infant (OR 20.97 [2.27–192.97])
1h OGTT >180 mg/dL: increased risk primary CS (OR 1.97 [1.08–3.55])
Elevated FBS, 1h and 2h OGTT: increase risk of NICU
admission (OR 2.18, 2.39 and 2.34 respectively)
No difference in adverse outcomes in women diagnosed using
IADPSG vs POGS criteria
1
3
2
Thursday, July 10, 14
23. Diabetes Care
35:529-535, 2012
Decision Analysis Model
No screening
50-g GCT then 100-g OGTT at 24-28 wks when indicated
IADPSG screening
1
3
2
Thursday, July 10, 14
24. No history of
DM or GDM
Strategy 1
No Screening
Strategy 2
Current Screening
Strategy 3
IADPSG Recommendations
50-g 1 h GCT at
24-28 weeks
>7.2 mmol/L
(130 mg/dL)
All others
insulin sensitive
100-g
3 hour OGTT
Two of the following:
Fasting >5.2 mmol/L (95 mg/dL), 1h
>10 mmol/L (180 mg/dL), 2h >8.6
mmol or 3h >7.8 mmol/L (140 mg/dL)
Overt DM or GDM
All others
insulin
sensitive
Fasting plasma
glucose
at first prenatal visit
>7.0 mmol/L
(126 mg/dL)
Overt DM
>5.1mmol/L
(92 mg/dL)
GDM
<5.1mmol/L
(92 mg/dL)
75-g 2h-OGTT
at 24-28 weeks
Fasting
>7.0 mmol/L
(126 mg/dL)
Overt DM
Fasting >5.1 mmol/L
(92 mg/dL)
1h >10.0 mmol/L
(180 mg/dL)
2h >8.5 mmol/L
(153 mg/dL)
GDM
All others
insulin
sensitive
Werner EF et al
Diabetes Care 2012;35:529-35
Thursday, July 10, 14
25. Assumptions
Additional prenatal monitoring, mitigating risks of
preeclampsia, shoulder dystocia and birth injury
1
2
Werner EF et al
Diabetes Care 2012;35:529-35
money matters by sufinawaz
http://www.freeimages.com/photo/865433
Intensive post delivery counseling and behavior
modification to reduce future diabetes risks
ICER = cost A - cost B
efficacy A - efficacy B
Thursday, July 10, 14
26. Figure from Nelson AL et al. Ann Intern Med 2009;151(9):662-7
$20,336 per
QALY gained
for IADPSG
screening
Cost-effective
only when post
delivery care
reduces
diabetes
incidence.
Werner EF et al
Diabetes Care 2012;35:529-35
Thursday, July 10, 14
27. Diabetes Care
35:529-535, 2012
... neither the current screening strategies
nor the IASDPG are cost-effective strategies
unless long-term maternal benefits are achieved.
“
Thursday, July 10, 14
28. Tablets vs insulin
white round pills by dimshilk
http://www.freeimages.com/photo/755944
Thursday, July 10, 14
29. Treatment of GDM: Glyburide compared to SC insulin therapy
and associated perinatal outcomes
Cheng YW et al. J Matern Fetal Neonatal Med 2012 Apr;25(4):379–384
I
M
O
P
Retrospective cohort study
GDM women (n=10,682) who required pharmaceutical
therapy and enrolled in Sweet Success California
Diabetes & Pregnancy Program 2001–2004
Glyburide (n=2073, 19.4%) vs
subcutaneous insulin (n=8609, 80.6%)
Neonates born to mothers on glyburide more likely to
be macrosomic and to be admitted to NICU
Thursday, July 10, 14
30. I
M
O
P 5 RCTs using “gestational diabetes” and “Metformin”
Effects of metformin vs insulin on glycemic control, maternal
and neonatal outcomes in GDM
Maternal: glycemic control, CS incidence, weight gain after enrollment,
pregnancy-induced hypertension, preeclampsia, preterm delivery, gestational age
at delivery, shoulder dystocia etc
Fetal: hypoglycemia, birth weight, NICU admission, LGA, SGA, respiratory
distress syndrome, hyperbilirubinemia etc
Meta-analysis using random effects model
PLoS One 8(5):e64585
Thursday, July 10, 14
33. PLoS One 8(5):e64585
Incidence of
preeclampsia
Lower in Metformin: average weight gain
& gestational age at delivery, rate of PIH
Higher in Metformin: preterm birth rate
No significant difference in preeclampsia
MATERNAL
Thursday, July 10, 14
36. Metformin is comparable to insulin in glycemic control and
neonatal outcomes. May be more suitable for mild GDM.
Weigh ?risk of preterm birth
PLoS One 8(5):e64585
Thursday, July 10, 14
38. Diabetes Care
35:50-56, 2012
I
M
OP 522 GDM women diagnosed
by 100-g OGTT enrolled in
Study of Women, Infant
Feeding & Type 2 Diabetes
(SWIFT)
Exclusive or mostly
breastfeeding vs formula feeding
Fasting plasma glucose,
fasting and 2h insulin
Prospective observational
cohort study
Thursday, July 10, 14
39. Gunderson EP et al. Diabetes Care 2012;35:50–56
Glucose tolerance categories among infant-feeding groups
at 6-9 weeks’ postpartum
Entire cohort n=522
Normal
PreDM
DM
Thursday, July 10, 14
40. Gunderson EP et al. Diabetes Care 2012;35:50–56
Obese women only n=241
Normal
PreDM
DM
Glucose tolerance categories among infant-feeding groups
at 6-9 weeks’ postpartum
Thursday, July 10, 14
41. Lactation may have favorable effects on glucose
metabolism and insulin sensitivity that may
reduce diabetes risk after GDM pregnancy.
“
Thursday, July 10, 14
42. I
M
O
P
Diabetes 2012;61:3167–3171
GDM women (n=304) participating in prospective German GDM
study recruited 1989–1999 & followed for up to 19 y postpartum
OGTT postpartum at 2 and 9 months; 2, 5, 8, 11, 15 and 19 y
or until diagnosis of diabetes
Development of diabetes
Prospective, observational
Thursday, July 10, 14
43. Ziegler et al.
Diabetes 2012;61:3167–3171
Cumulative life-table risk of postpartum diabetes in islet
autoantibody-negative GDM who breastfed
No breastfeeding
Breastfeeding <3 mos.
Breastfeeding >3 mos.
Thursday, July 10, 14
44. Diabetes 2012;61:3167–3171
Median time to diabetes in autoantibody-negative breastfeeding
women is 12.3 y vs 2.3 y in women who did not breastfeed.
Breastfeeding should be encouraged among these
women because it offers a safe and feasible
low-cost intervention to reduce the risk of
subsequent diabetes in this high-risk population.
“
Thursday, July 10, 14
45. Implications of
using IADPSG criteria
women serie 2 by asterisco
http://www.freeimages.com/photo/313127
www.slideshare.net/isiptan
Tablets
vs insulin
white round pills by dimshilk
http://www.freeimages.com/photo/755944
Lactation
after GDM
Lactation2 by carin
http://www.freeimages.com/photo/161052
Thursday, July 10, 14