2/13/2018 Update on Gestational Diabetes Lorie M. Harper, MD, MSCI - - PDF document

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

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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

• f 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 Risk p Any Serious Perinatal Complication 7 (1%) 23 (4%) 0.32 (0.14-0.73) 0.004 Death 5 (1%)

• 0.06

Shoulder Dystocia 7 (1%) 16 (3%) 0.45 (0.19-1.09) 0.07 Admission to Nursery 357 (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 Labor 189 (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 Risk p Gestational Age at Birth 39.0 ± 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 Birth Trauma 3 (0.6%) 6 (1.3%) 0.48 (0.10-2.20) 0.33

MFMU

Treatment (n=485) Control (n=473) Relative Risk p 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 Risk p 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 Coustan NDDG Fasting 95 105 One Hour 180 190 Two Hour 155 165 Three Hour 140 145 Requires: 2 abnormal values

Diagnostic Thresholds

Carpenter Coustan NDDG 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 PO St Study Cooperative Research Group. N En 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

• utcomes
• One Step

Based on perinatal

• utcomes

Two Step versus One Step

• Two Step

Not based on perinatal

• utcomes

4-8% prevalence of GDM

• One Step

Based on perinatal

• utcomes

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

• utcomes

4-8% prevalence of GDM Evidence of treatment benefit

• One Step

Based on perinatal

• utcomes

16% prevalence of GDM Treatment benefit not examined

Two Step versus One Step

• Two Step

Not based on perinatal

• utcomes

4-8% prevalence of GDM Evidence of treatment benefit Screening step without fasting

• One Step

Based on perinatal

• utcomes

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

• utcomes

4-8% prevalence of GDM Evidence of treatment benefit Screening step without fasting Two visits

• One Step

Based on perinatal

• utcomes

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=100 p Primary Cesarean 23.5% 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

• utcomes

4-8% prevalence of GDM Evidence of treatment benefit Screening step without fasting Two visits

• One Step

Based on perinatal

• utcomes

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 Dystocia 1.8% 5.7% 1.0% 1.6% 0.43 Cesarean Delivery 27.9% 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

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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
• bese 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
• bese 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

• utcomes

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?