2/13/2018€¦ · induction of labor 130 (27.3%) 122 (26.8%) 1.02 (0.81-1.29) 0.86 cesarean...
TRANSCRIPT
2/13/2018
1
Update on Gestational Diabetes
Lorie M. Harper, MD, MSCI
Department of Obstetrics & Gynecology
Division of Maternal-Fetal Medicine
2/18/2018
Disclosure
I have no financial conflicts of interest.
Objectives
Identify appropriate screening strategies for
gestational diabetes
Describe the risks associated with GDM and
benefits of treatment
Describe the management of GDM, during & after
pregnancy
2/13/2018
2
Outline
What is GDM?
What are the consequences of GDM?
Are there benefits to treating GDM?
How should I screen for GDM?
When should I screen for GDM?
How should I manage GDM?
What is GDM?
Carbohydrate intolerance of
variable severity with onset or
first recognition during pregnancy
GDM Complications
Maternal
Hypertensive disorders
of pregnancy
Increased risk of
cesarean
Neonatal
Stillbirth
Macrosomia
Shoulder dystocia
Birth trauma
Hypoglycemia
Hyperbilirubinemia
Obesity
Diabetes
2/13/2018
3
Harms of Diagnosing/Treating GDM
More clinic visits
Time away from work
“Loss of control”
“Medicalization” of pregnancy
Increased induction
Iatrogenic cesarean
Iatrogenic NICU admissions
Benefits of Treating GDM
Two randomized controlled trials:
ACHOIS – Crowther et al, NEJM 2005
MFMU – Landon et al, NEJM 2009
ACHOIS
Diagnosis of GDM:
Two-step screening (50g followed by 75g)
Normal fasting
2-hour <198 mg/dL
=MILD GDM
Randomized
Blinded
2/13/2018
4
ACHOIS
Treatment
(n=506)
Routine Care
(n=524)
Relative
Riskp
Any Serious
Perinatal
Complication
7 (1%) 23 (4%)0.32
(0.14-0.73)0.004
Death 0 5 (1%) -- 0.06
Shoulder Dystocia 7 (1%) 16 (3%)0.45
(0.19-1.09)0.07
Admission to
Nursery357 (71%) 321 (61%)
1.15
(1.05-1.26)0.002
LGA 68 (13%) 115 (22%)0.62
(0.47-0.81)<0.001
Macrosomia 49 (10%) 110 (21%)0.47
(0.34-0.64)<0.001
Hypoglycemia 35 (7%) 27 (5%)1.42
(0.87-2.32)0.16
ACHOIS
Treatment
(n=506)
Routine Care
(n=524)Relative Risk p
Induction of
Labor189 (39%) 150 (29%)
1.31
(1.10-1.56)0.002
Cesarean 152 (31%) 164 (32%)0.96
(0.80-1.16)0.70
Preeclampsia 58 (12%) 93 (18%)0.70
(0.51-0.95)0.02
MFMU
Diagnosis of GDM
Two step screening (50g followed by 100g)
Normal fasting (<95 mg/dL)
At least 2 abnormal: 1-hour >180, 2-hour >155, 3-
hour >140
=MILD GDM
Randomized
Blinded
2/13/2018
5
MFMU
Treatment
(n=485)
Control
(n=473)
Relative
Riskp
Gestational Age at
Birth39.0 ± 1.8 38.9 ± 1.8 0.87
Composite 149 (32.4%) 163 (37.0%)0.87
(0.72-1.07)0.14
Hypoglycemia 62 (16.3%) 55 (15.4%)1.06
(0.73-1.53)0.75
Hyperbilirubinemia 43 (9.6%) 54 (12.9%)0.74
(0.49-1.12)0.12
C-peptide 75 (17.7%) 92 (22.8%)0.78
(0.57-1.05)0.07
Death 0 0
Birth Trauma 3 (0.6%) 6 (1.3%)0.48
(0.10-2.20)0.33
MFMU
Treatment
(n=485)
Control
(n=473)
Relative
Riskp
Birth Weight 3302 ± 502 3408 ± 589<
0.001
Macrosomia 28 (5.9%) 65 (14.3%)0.41
(0.26-0.66)
<
0.001
LGA 34 (7.1%) 66 (14.5%)0.49
(0.32-0.76)
<
0.001
Fat Mass 427 ± 198 464 ± 222 0.003
Shoulder Dystocia 7 (1.5%) 18 (4.0%)0.37
(0.14-0.97)0.02
MFMU
Treatment
(n=485)
Control
(n=473)
Relative
Riskp
Induction of Labor 130 (27.3%) 122 (26.8%)1.02
(0.81-1.29)0.86
Cesarean Delivery 128 (26.9%) 154 (33.8%)0.79
(0.64-0.99)0.02
Preeclampsia or
Gestational
Hypertension
41 (8.6%) 62 (13.6%)0.63
(0.42-0.96)0.01
2/13/2018
6
Benefits of Treating GDM
ACHOIS MFMU
Reduced Serious
Perinatal Morbidity?YES
MAYBE
(shoulder dystocia)
Reduced Macrosomia,
LGA, Birth Weight?YES YES
Reduced Neonatal
Hypoglycemia?NO NO
Reduced Neonatal Fat
Mass?-- YES
Induction of Labor INCREASED No Difference
Reduced Cesarean? NO YES
Reduced Preeclampsia? YES YES
Screening for GDM
Old versus “New”
Screening for GDM
Two Step
50-g load, 1-hour
100-g load, 3-hour
Carpenter-Coustan
National Diabetes Data
Group
One Step (IADPSG)
75-g load, 2-hour
2/13/2018
7
Diagnostic Thresholds
Carpenter
CoustanNDDG
Fasting 95 105
One Hour 180 190
Two Hour 155 165
Three Hour 140 145
Requires: 2 abnormal values
Diagnostic Thresholds
Carpenter
CoustanNDDG IADPSG
Fasting 95 105 92
One Hour 180 190 180
Two Hour 155 165 153
Three Hour 140 145 --
Requires: 2 abnormal values 1 abnormal value
Where did the new IADPSG criteria
come from?
Hyperglycemia & Adverse Pregnancy
Outcomes
Prospective observational study
75-g glucose test between 24-32 weeks
Primary outcomes:
Birth weight >90th percentile
Primary cesarean
Neonatal hypoglycemia
Cord blood C-peptide >90th percentile
2/13/2018
8
HAPO: What we hoped to find
HAPO: What we did find
The HAPO Study Cooperative
Research Group. N Engl J Med
2008;358:1991-2002.
IADPSG
Odds Ratio for Primary Outcome Prevalence of GDM
1.5 25%
1.75 16.1%
2.0 8.8%
Glucose Measure
Glucose
Concentration
(mg/dL)
Cumulative
% Above Threshold
Fasting 92 8.3%
1-Hour 180 14.0%
2-Hour 153 16.1%
IADPSG, Diabetes Care
2010; 33(3): 676-682
2/13/2018
9
Two Step versus One Step
Two Step
Not based on perinatal
outcomes
One Step
Based on perinatal
outcomes
Two Step versus One Step
Two Step
Not based on perinatal
outcomes
4-8% prevalence of
GDM
One Step
Based on perinatal
outcomes
16% prevalence of
GDM
Implications of Increased Prevalence
Increased prenatal visits - >1 million
Increased patient education visits – 450,000
Increased antenatal testing – 1 million
2/13/2018
10
Two Step versus One Step
Two Step
Not based on perinatal
outcomes
4-8% prevalence of
GDM
Evidence of treatment
benefit
One Step
Based on perinatal
outcomes
16% prevalence of
GDM
Treatment benefit not
examined
Two Step versus One Step
Two Step
Not based on perinatal
outcomes
4-8% prevalence of
GDM
Evidence of treatment
benefit
Screening step without
fasting
One Step
Based on perinatal
outcomes
16% prevalence of
GDM
Treatment benefit not
examined
All women must do
fasting test
Benefits of One Step Testing
36% reduction in lab workload
Scheduling issues for all women to come in fasting
Overall increase in cost (42%)
2/13/2018
11
Two Step versus One Step
Two Step
Not based on perinatal
outcomes
4-8% prevalence of
GDM
Evidence of treatment
benefit
Screening step without
fasting
Two visits
One Step
Based on perinatal
outcomes
16% prevalence of
GDM
Treatment benefit not
examined
All women must do
fasting test
One visit
Benefits of One Step Testing
No loss to follow up after an elevated one hour
No delay in diagnosis
Delay in Diagnosis Created by 2-Step
≤7 Days
n=306
8-14 Days
n=143
>14 Days
n=100p
Primary
Cesarean23.5% 25.4% 13.0% 0.12
Preeclampsia 10.8% 8.4% 7.0% 0.22
Preterm Birth 16.3% 14.7% 15.0% 0.68
Birth Weight 3328 ± 649 3283 ± 575 3375 ± 647 0.53
Macrosomia 12.4% 9.1% 12.0% 0.68
Birth Injury 2.0% 1.4% 4.1% 0.63
Siegel et al, Am J Perinatol.
2017; 34(6): 557-562
2/13/2018
12
Two Step versus One Step
Two Step
Not based on perinatal
outcomes
4-8% prevalence of
GDM
Evidence of treatment
benefit
Screening step without
fasting
Two visits
One Step
Based on perinatal
outcomes
16% prevalence of
GDM
Treatment benefit not
examined
All women must do
fasting test
One visit
Two Step Testing:
Which cutoffs should we use?
One Hour Glucose Challenge Test
50-gram glucose load
Blood draw at 1-hour
No need to fast
Cut off options:
130
135
140
Higher false positive rate, lower positive predictive
value, more 3-hour GTTs performed
Lower false positive rate, improved positive
predictive value, fewer 3-hour GTTs performed
2/13/2018
13
Carpenter-Coustan vs NDDG
Carpenter-Coustan criteria diagnoses 50% more
women with GDM
Carpenter Coustan used in the MFMU trial
Carpenter Coustan NDDG
Fasting 95 105
One Hour 180 190
Two Hour 155 165
Three Hour 140 145
Requires: 2 abnormal values
Carpenter-Coustan vs NDDG
Carpenter Coustan
(n=389)
NDDG
(n=542)P
Treated
(n=196)
Usual Care
(n=193)
Treated
(n=280)
Usual Care
(n=262)Interaction
PIH 8.2% 14.0% 8.9% 13.4% 0.73
Shoulder
Dystocia1.8% 5.7% 1.0% 1.6% 0.43
Cesarean
Delivery27.9% 30.2% 25.5% 38.9% 0.08
LGA 6.1% 15.7% 8.7% 13.0% 0.17
• Direction of effect favors treatment regardless of
which diagnostic criteria used used
Harper et al for MFMU,
Obstet Gynecol, 2016; 127(5)
Diagnostic Criteria Summary
NICHD, ACOG endorse two step screening
(although one step is acceptable)
No specific two step screening cutoffs endorsed
although there is evidence of treatment effect using
Carpenter Coustan criteria
2/13/2018
14
Timing of Screening
When to Screen
Routine Screening:
24-28 weeks
Balance between:
Increasing insulin resistance
Time for treatment
Early Screening
Goals:
Detect undiagnosed pre-gestational diabetes
Detect early onset GDM
Improve perinatal outcomes associated with
DM/GDM:
PIH, shoulder dystocia, LGA, cesarean
2/13/2018
15
Early Screening
Consequences of early screening:
Additional visits
Additional costs of treating GDM – longer time
diagnosed
Potential automatic “pregestational DM” diagnosis
More likely to get insulin
Early Screening - Benefits
No proven benefits
No published RCTs
Retrospective studies have largely focused on
diagnostic criteria – not perinatal outcomes
Few studies that examine perinatal outcomes do not
demonstrate a benefit
Early Screening
When:
At first prenatal visit
2/13/2018
16
Early Screening – Who?
Who?
ACOG adapted from ADA
Early Screening – Who?
“Consider testing all women who are overweight or
obese and have one of the following additional risk
factors”:
Physical inactivity
First degree relative
High-risk race (African American, Latino, Native
American, Asian American, Pacific Islander)
Previous infant >4000g
Previous GDM
Early Screening – Who?
“Consider testing all women who are overweight or
obese and have one of the following additional risk
factors”:
Hypertension
HDL<35 mg/dL or triglyceride >250 mg/dL
PCOS
A1c >5.7% or impaired glucose tolerance
Cardiovasular disease
“Other conditions associated with insulin
resistance”
2/13/2018
17
Early Screening – How?
Options:
HbA1c
75-g GTT (fasting, two hour)
IADSPG
Two step testing
Are the cutoffs the same at the first prenatal visit
compared to 24-28 weeks?
Early Screening – How?
I passed my first one hour…
Recommend repeat screen at 24-28 weeks
I failed my first one hour but passed my three hour
Recommend repeat screen at 24-28 weeks
Can go straight to 3-hour or repeat 1-hour
Early Screening Summary
No evidence to support it
ACOG & ADA recommend for “high risk” groups
No specific recommendations on best method of
screening
Repeat screening at 24-28 weeks if passed
2/13/2018
18
Pharmacologic Therapy
Management of GDM
Diet counseling
30-40% complex carbohydrates
20-30% fat
20-30% protein
Exercise
Blood glucose monitoring
Fasting & post-prandial (1 or 2 hours)
Management of GDM
Blood sugar goals:
Fasting: <95 mg/dL
1-Hour Post Prandial: <140 mg/dL
2-Hour Post Prandial: <120 mg/dL
Start medications when >50% of blood sugars >goal
2/13/2018
19
Medication Options
ACOG:
Insulin
Metformin
Glyburide
SMFM
Metformin
“reasonable and safe
first-line”
More data needed
Insulin
Advantages
Does not cross the
placenta
Essentially never fails
Recommended by
ADA
Disadvantages
Expensive
Hurts
Risk of hypoglycemia
Requires teaching
Insulin
Lantus/Levemir: Long acting, Qday dosing
Good for patients who have high fasting values
but not too high postprandial values
Aspart/Lispro: Short acting, give immediately before
meals
Good for high postprandial values
NPH: Intermediate acting, BID-TID dosing
2/13/2018
20
Insulin
NPH: Intermediate acting, BID-TID dosing
Less expensive
Can be given at night to control fasting
Can be given in AM for all-day control
Regular: 30-60 minutes onset
Less expensive than Aspart/Lispro
Can be given prior to meals for PP control
Metformin
Biguanide
Increases insulin sensitivity
No hypoglycemia
Start at lower dose (500 mg BID) & increase slowly
to avoid GI side effects
Crosses the placenta
Higher failure rate than insulin
Metformin
ACOG’s concerns:
Minimal data on long-term outcomes
But data that we have suggests no adverse
neurodevelopmental or cardiometabolic
outcomes
Questionable increase in preterm birth – not
consistent across studies
2/13/2018
21
Glyburide
Sulfonylurea: Increases insulin secretion
Can cause hypoglycemia
Crosses placenta
May cause neonatal hypoglycemia at higher doses
May have worse neonatal outcomes compared to
insulin
Limited data on long-term safety
Pharmacologic Management
Summary
ACOG: First line insulin
SMFM: Oral medications probably reasonable
Practical:
Some patients are simply not candidates for oral
therapy – very high fastings (>100), very high
postprandial values (>200), risk factors for
pregestational DM (prior GDM, early diagnosis)
Other Antepartum Management Issues
2/13/2018
22
Fetal Monitoring
Antenatal Testing:
A1DM: >40 weeks
A2DM: 1-2/weekly antenatal testing after 32
weeks or at diagnosis, whichever is first
Growth:
Ultrasound within 3 weeks of delivery
Delivery
Timing:
A1DM: By 41 weeks
A2DM well controlled: Between 39-40 weeks
A2DM, poorly controlled: Early term may be
reasonable (37-39 weeks)
Mode of Delivery:
“Counsel regarding risks and benefits of
cesarean” if >4500g
Intrapartum Management
Goal is for <120 mg/dL at time of delivery
May require insulin drip
Do not withhold D5 to control blood sugars –
creates ketosis
2/13/2018
23
Post-Partum
15-20% of GDM will have glucose intolerance post-
partum
Test at postpartum visit (75g, two hour)
Need annual testing for Type 2 DM
Thank you
Questions?