2/13/2018. Update on Gestational Diabetes. Disclosure. Objectives. I have no financial conflicts of interest.

Transcription

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 1

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

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 3

4 ACHOIS Any Serious Perinatal Complication Treatment (n=506) Routine Care (n=524) 7 (1%) 23 (4%) Relative Risk 0.32 ( ) p Death 0 5 (1%) Shoulder Dystocia 7 (1%) 16 (3%) Admission to Nursery 357 (71%) 321 (61%) LGA 68 (13%) 115 (22%) Macrosomia 49 (10%) 110 (21%) Hypoglycemia 35 (7%) 27 (5%) 0.45 ( ) 1.15 ( ) 0.62 ( ) 0.47 ( ) 1.42 ( ) <0.001 < ACHOIS Induction of Labor Treatment (n=506) Routine Care (n=524) 189 (39%) 150 (29%) Cesarean 152 (31%) 164 (32%) Preeclampsia 58 (12%) 93 (18%) Relative Risk 1.31 ( ) 0.96 ( ) 0.70 ( ) p Diagnosis of GDM MFMU 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 4

5 MFMU Gestational Age at Birth Treatment (n=485) Control (n=473) Relative Risk 39.0 ± ± Composite 149 (32.4%) 163 (37.0%) Hypoglycemia 62 (16.3%) 55 (15.4%) Hyperbilirubinemia 43 (9.6%) 54 (12.9%) C-peptide 75 (17.7%) 92 (22.8%) Death 0 0 Birth Trauma 3 (0.6%) 6 (1.3%) 0.87 ( ) 1.06 ( ) 0.74 ( ) 0.78 ( ) 0.48 ( ) p MFMU Treatment (n=485) Control (n=473) Birth Weight 3302 ± ± 589 Macrosomia 28 (5.9%) 65 (14.3%) LGA 34 (7.1%) 66 (14.5%) Relative Risk 0.41 ( ) 0.49 ( ) p < < < Fat Mass 427 ± ± Shoulder Dystocia 7 (1.5%) 18 (4.0%) 0.37 ( ) 0.02 MFMU Treatment (n=485) Control (n=473) Induction of Labor 130 (27.3%) 122 (26.8%) Cesarean Delivery 128 (26.9%) 154 (33.8%) Preeclampsia or Gestational Hypertension 41 (8.6%) 62 (13.6%) Relative Risk 1.02 ( ) 0.79 ( ) 0.63 ( ) p

6 Benefits of Treating GDM Reduced Serious Perinatal Morbidity? Reduced Macrosomia, LGA, Birth Weight? Reduced Neonatal Hypoglycemia? Reduced Neonatal Fat Mass? ACHOIS YES YES NO MFMU MAYBE (shoulder dystocia) YES NO -- 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 6

7 Diagnostic Thresholds Carpenter Coustan NDDG Fasting One Hour Two Hour Three Hour Requires: 2 abnormal values Diagnostic Thresholds Carpenter Coustan NDDG IADPSG Fasting One Hour Two Hour Three Hour 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 weeks Primary : Birth weight >90 th percentile Primary cesarean Neonatal hypoglycemia Cord blood C-peptide >90 th percentile 7

8 HAPO: What we hoped to find HAPO: What we did find The HAPO Study Cooperative Research Group. N Engl J Med 2008;358: IADPSG Odds Ratio for Primary Outcome Prevalence of GDM % % % Glucose Measure Glucose Concentration (mg/dl) Cumulative % Above Threshold Fasting % 1-Hour % 2-Hour % IADPSG, Diabetes Care 2010; 33(3):

9 Two Step versus One Step Two Step Not based on perinatal One Step Based on perinatal Two Step versus One Step Two Step Not based on perinatal 4-8% prevalence of GDM One Step Based on perinatal 16% prevalence of GDM Implications of Increased Prevalence Increased prenatal visits - >1 million Increased patient education visits 450,000 Increased antenatal testing 1 million 9

10 Two Step versus One Step Two Step Not based on perinatal 4-8% prevalence of GDM Evidence of treatment benefit One Step Based on perinatal 16% prevalence of GDM Treatment benefit not examined Two Step versus One Step Two Step Not based on perinatal 4-8% prevalence of GDM Evidence of treatment benefit Screening step without fasting One Step Based on perinatal 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%) 10

11 Two Step versus One Step Two Step Not based on perinatal 4-8% prevalence of GDM Evidence of treatment benefit Screening step without fasting Two visits One Step Based on perinatal 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= 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 ± ± ± 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):

12 Two Step versus One Step Two Step Not based on perinatal 4-8% prevalence of GDM Evidence of treatment benefit Screening step without fasting Two visits One Step Based on perinatal 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: 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 12

13 Carpenter-Coustan vs NDDG Carpenter Coustan Carpenter-Coustan criteria diagnoses 50% more women with GDM Carpenter Coustan used in the MFMU trial NDDG Fasting One Hour Two Hour Three Hour Requires: 2 abnormal values Carpenter-Coustan vs NDDG Carpenter Coustan (n=389) Treated (n=196) Usual Care (n=193) Treated (n=280) NDDG (n=542) Usual Care (n=262) P Interaction PIH 8.2% 14.0% 8.9% 13.4% 0.73 Shoulder Dystocia Cesarean Delivery 1.8% 5.7% 1.0% 1.6% % 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 13

14 Timing of Screening When to Screen Routine Screening: weeks Balance between: Increasing insulin resistance Time for treatment Goals: Early Screening Detect undiagnosed pre-gestational diabetes Detect early onset GDM Improve perinatal associated with DM/GDM: PIH, shoulder dystocia, LGA, cesarean 14

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 Few studies that examine perinatal do not demonstrate a benefit When: At first prenatal visit Early Screening 15

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 16

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 weeks? Early Screening How? I passed my first one hour Recommend repeat screen at weeks I failed my first one hour but passed my three hour Recommend repeat screen at 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 weeks if passed 17

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 18

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 19

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: minutes onset Less expensive than Aspart/Lispro Can be given prior to meals for PP control Biguanide Metformin 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 But data that we have suggests no adverse neurodevelopmental or cardiometabolic Questionable increase in preterm birth not consistent across studies 20

21 Glyburide Sulfonylurea: Increases insulin secretion Can cause hypoglycemia Crosses placenta May cause neonatal hypoglycemia at higher doses May have worse neonatal 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 21

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 Timing: A1DM: By 41 weeks Delivery A2DM well controlled: Between 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 22

23 Post-Partum 15-20% of GDM will have glucose intolerance postpartum Test at postpartum visit (75g, two hour) Need annual testing for Type 2 DM Thank you Questions? 23