2/13/2018

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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%)

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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

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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

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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

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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

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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

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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”

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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

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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

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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

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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

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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

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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

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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?