6/17/2017 The Ever-Changing Approaches to Diabetes in Pregnancy I have nothing to disclose. Kirsten E. Salmeen, MD Assistant Professor Obstetrics, Gynecology & Reproductive Sciences Maternal-Fetal Medicine Approaches are “Ever-Changing” Due To: GDMA1 • Relative lack of very high-quality data Type 1 Diabetes GDMA2 • Disagreement about definitions of “disease” • Wide variability in resources Pre-Diabetes Type 2 1
6/17/2017 What is the average fasting glucose for healthy pregnant woman who do not have diabetes? 35% The Data We Have A. 90 – 95 mg/dL 31% B. 85 – 90 mg/dL 23% C. 80 – 85 mg/dL 11% D. 75 – 80 mg/dL L L L L d d d d / / / / g g g g m m m m 5 0 5 0 9 9 8 8 – – – – 0 5 0 5 9 8 8 7 What is the average 1-hour postprandial Normal Glucose In Pregnancy: Non Diabetics glucose for healthy pregnant woman who do not have diabetes? A. 130 – 140 mg/dL 48% 37% B. 120 – 130 mg/dL C. 110 – 120 mg/dL D. 100 – 110 mg/dL 12% 2% L L L L d d d d / / / / g g g g m m m m 0 0 0 0 4 3 2 1 1 1 1 1 – – – – 0 0 0 0 3 2 1 0 1 1 1 1 Hernandez et al. Diabetes Care. 2011;34(7):1660-8. 2
6/17/2017 HAPO Results Increasing maternal glycemia is associated with increased risk of maternal and fetal complications. Blinded study of ~25,000 women at 15 centers, 9 countries Primary predictor: Levels of hyperglycemia Primary outcomes: Birth weight > 90%ile, primary CD, neonatal hypoglycemia, cord-blood C-peptide level HAPO Study Cooperative Research Group. N Engl J Med. 2008;358(19):1991-2002. HAPO Study Cooperative Research Group. N Engl J Med. 2008;358(19):1991-2002. Hyperglycemia & Pregnancy Hyperglycemia & Pregnancy Outcomes Outcomes 2 hour 2 hour 2 hour 2 hour ≥ Odds Outcome (%) 95% CI Fasting < Fasting Fasting Fasting ≥ Odds < 102 102-114 115-128 130 Ratio Outcome (%) 95% CI 74 74-77 79-81 83 Ratio Birthweight ≥ 22.9 27.4 28.8 32.3 1.16 1.01-1.34 Birth weight ≥ 4000 g 23.4 27.9 28.5 31.7 1.14 1.06-1.22 4000 g Birthweight > 5.2 5.3 5.6 8.6 1.16 1.01-1.34 Birth weight ≥ 4500 g 4.3 6.3 6.8 8.1 1.23 1.08-1.40 4500 g LGA 16.0 20.7 21.1 27.2 1.23 1.13-1.33 LGA 17.2 18.9 22.7 25.6 1.19 1.10-1.29 PIH/PreE 4.8 6.9 8.4 7.2 1.16 1.02-1.31 PIH/PreE 5.8 6.6 7.1 7.9 1.12 0.99-1.26 Shoulder 0.4 1.2 1.8 2.9 1.78 1.32-2.40 Shoulder Dystocia 1.4 0.8 1.7 2.2 1.21 0.92-1.62 Dystocia Jensen AJOG 2001 Jensen AJOG 2001 3
6/17/2017 Crowther – Trial of Treatment for GDM Landon – Trial of Treatment for GDM Intervention Routine Care Adjusted RR or Adjusted Intervention Control Group Group N= 490 N= 510 Treatment Effect p-value Group N = 485 N = 473 Relative Risk p-value (%) (%) (%) (%) *Any serious perinatal 1 4 0.33 (0.14 – 0.75) 0.01 NICU Admission 9 11.6 0.77 (0.51 – 1.18) 0.19 complication Admission to NICU 71 61 1.13 (1.03 – 1.23) 0.04 Macrosomia 5.9 14.3 0.41 (0.26 – 0.66) < 0.001 Neonatal Macrosomia 10 21 0.47 (0.34 – 0.64) < 0.001 5.3 6.8 0.77 (0.44 – 1.36) 0.32 Hypoglycemia Neonatal hypoglycemia 7 5 1.42 (0.87 – 2.32) 0.16 Shoulder Dystocia 1.5 4.0 0.37 (0.14 – 0.97) 0.02 Cesarean Delivery 26.9 33.8 0.79 (0.64 – 0.99) 0.02 Preeclampsia 12 18 0.7 (0.51 – 0.95) 0.02 Preeclampsia or Cesarean Delivery 31 32 0.97 (0.81 – 1.16) 0.73 8.6 13.6 0.63 (0.42 – 0.96) 0.01 GHTN * One or more of: death, shoulder dystocia, bone fracture, nerve palsy Landon et al. N Eng J Med. 2009;361:1339-48. Crowther et al. N Engl J Med. 2005;352:2477-86. Rowan - Metformin versus Insulin Moore – Metformin versus Glyburide Metformin* Insulin Group N Group N = 363 = 370 Relative Risk p-value • 150 women randomized to Metformin or Glyburide (%) (%) • Outcomes: EGA at delivery, NICU admission, neonatal & Composite 116 (32.0) 119 (32.2) 0.99 (0.80 – 1.23) 0.95 Outcome** maternal hypoglycemia were the same Any neonatal blood glucose < 28.8 12 (3.3) 30 (8.1) 0.41 (0.21 – 0.78) 0.008 • Birthweight was ~ 200g larger in the Glyburide group mg/dL • Cesarean delivery was higher in the Metformin group Birth weight - g 3372 +/- 572 3413 +/- 569 0.33 • 34.7% of women in the Metformin group versus 16.2% of Birth weight > 70 (19.3) 69 (18.6) 0.83 90%ile women in the Glyburide group did not achieve adequate glycemic control * 168 patients received metformin PLUS insulin ** Composite: neonatal hypoglycemia, respiratory distress, need for phototherapy, birth trauma, 5 min Apgar < 7, birth < 37 weeks Rowan et al. N Engl J Med. 2008;358:2003-15 Moore et al. Obstet Gynecol. 2010;115:55-9. 4
6/17/2017 Nachum – Glyburide vs Metformin and Their Combination Wouldes: • Randomized trial of ~ 100 women Neurodevelopmental Outcomes for • 53 started with Glyburide: Metformin & Insulin • 6 (11%) failed due to hypoglycemia • 12 (23%) failed due to inadequate control • 2-yr follow-up of 211 children whose • 51 started with Metformin • 1 (2%) failed due to GI side-effects mothers were treated with insulin or • 14 (28%) failed due to inadequate control metformin • Treatment success after 2 nd therapy was higher in the metformin • No differences in neurodevelopmental group (87%) vs the Glyburide group (50%) scores examined using Bayley Scales • The combination of the drugs reduced the need for insulin from 33% to 11% Nachum et al. Diabetes Care 2017 Wouldes et al. Arch Dis Child Fetal Neonatal Ed 2016 Induction of Labor Wang – RCT of Exercise • Rosenstein: Infant mortality rates at 39 weeks are lower than overall • 300 overweight/obese Chinese women, mortality risk of expectant management. randomized to exercise (3 times per week of 30 min cycling or control (usual daily activities) • Primary outcome was incidence of GDM • Women in the exercise group were diagnosed with GDM 22% versus 41% in the control group Wang et al. AJOG 2017 Rosenstein et al. Am J Obstet Gynecol. 2012;206:309.e1-7. 5
6/17/2017 Things we really don’t know Approaches are “Ever-Changing” Due To: • The best diets for women with GDM • Relative lack of very high-quality data • The best treatment options • Risks associated with mild, isolated fasting hyperglycemia • Disagreement about definitions of “disease” • Risk of poor outcomes by overall sugar control • Wide variability in resources • Attributable long-term risks for mothers and infants What constitutes disease ? What primary cesarean section rate defines a bad outcome from disease ? Dichotomization of a continuous process is bound to result in disagreement HAPO Study Cooperative Research Group. N Engl J Med. 2008;358(19):1991-2002. 6
6/17/2017 What birth weight defines a bad outcome from disease ? Who Decides? HAPO Study Cooperative Research Group. N Engl J Med. 2008;358(19):1991-2002. Lack of unambiguous evidence that aggressive diagnosis improves clinically important pregnancy outcomes • The Landon study included women with 2 abnormal values on a 3-hour “All pregnant patients should be screened for GDM, • Studies of treatment are within the confines of strict clinical trials whether by the patient’s medical history, clinical risk factors, or laboratory screening test results to • No study has compared outcomes between determine blood glucose levels.” women who rule-in by 1-step approach but rule out by 2-step approach 7
6/17/2017 You Decide! Patient population: • Risk • Health literacy • Willingness & ability to make changes “Parachutes reduce the risk of injury after gravitational • Relative degree of concern about GDM challenge, but their Resources: effectiveness has not been • Nutrition proved with randomised controlled trials.” • Education • Provider capacity One-Step vs. Two-Step Testing The Nature of Screening Tests Two-Step • Screening is the identification of an asymptomatic disease, One-Step Step 1: harmful condition or risk factor. Non-Fasting, 50 g, 1 hr serum • When deciding how to screen, the following must be Fasting, 75 g, 1 & 2 hr serum glucose glucose measurement measurement considered: ≥ 130/140 mg/dL � Step 2 - Burden of suffering caused by the condition 1+ abnormal value � GDM Step 2: Fasting, 100 g, 3 hr glucose test - Therapeutic interventions available GDM prevalence ~ 20% 2+ abnormal values � GDM - Performance of available screening tests GDM prevalence ~ 5-10% Fletcher et al. Clinical Epidemiology: The Essentials, 5 th Ed, Lippincott Williams & Wilkins 2013 8
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