Outline / Objectives Pregnancy in the U.S. Epidemiology of GDM - PowerPoint PPT Presentation

6/9/2018 Disclosures Gestational Diabetes: Pill or Shot? An Evidence-Based Update No financial disclosures related to this topic Medical Advisor to Mindchild, Celmatix Bob’s Red Mill Aaron B. Caughey, MD, PhD Professor and Chair ACOG Department of Obstetrics & Gynecology Oregon Health & Science University Epidemiology of Diabetes during Outline / Objectives Pregnancy in the U.S.  Epidemiology of GDM  Management of GDM  154,000 (4%) of all pregnancies  Diet and exercise  Insulin  135,000 (88%) due to GDM  Oral hypoglycemic agents  12,000 (8%) due to Type 2 DM  Controversy 7,000 (4%) due to Type 1 DM  ACOG practice bulletin. Gestational Diabetes. Obstet Gynecol 2001;93:525-34 ADA position statement. Standards of Medical Care in Diabetes. Diabetes Care 2006;29:S4-42 1

6/9/2018 GDM: Obstetric Considerations GDM: Perinatal Considerations  GDM associated with  GDM associated with  Fetal macrosomia  Birth trauma  Gestational hypertension  Metabolic abnormalities  Preeclampsia  Hypoglycemia  Operative deliveries  Hyperbilirubinemia/polycythemia  Postpartum development of Type 2 DM  Hypocalcemia  Respiratory distress syndrome  Preterm delivery  Perinatal mortality Crowther CA et al. N Engl J Med 2005;352:2477-86. Casey BM et al. Obstet Gynecol 1997;90:867-73. Crowther CA et al. N Engl J Med 2005;352:2477-86 Yang X et al. Diabetes Care 2002;9:1619-24. Casey BM et al. Obstet Gynecol 1997;90:867-73 Yang X et al. Diabetes Care 2002;9:1619-24 GDM: Postnatal Considerations  Metabolic syndrome evaluated in a longitudinal cohort of 179 children (at age 6,7,9,11) Boney CM et al. Metabolic syndrome in childhood: Association with birthweight, maternal obesity and GDM. Pediatrics 2005;115:e290-6 2

6/9/2018 GDM: Universal Screening Management of GDM USPSTF - Recommendations and Evidence  Nutrition therapy  Home self glucose monitoring The USPSTF recommends screening for  Medical therapy if glycemic control not gestational diabetes mellitus (GDM) in achieved with diet/exercise asymptomatic pregnant women after 24 weeks of  Subcutaneous insulin gestation. (B recommendation)  Oral hypoglycemic agents  Glyburide The USPSTF concludes that the current evidence  Metformin  Antenatal monitoring is insufficient to assess the balance of benefits and harms of screening for GDM in asymptomatic pregnant women before 24 weeks of gestation. ACOG practice bulletin. Gestational Diabetes. Obstet Gynecol 2001 ACOG practice bulletin #190. Gestational Diabetes. Obstet Gynecol 20017, 2018 (I statement) Gabbe SG. Management of diabetes mellitus by ObGyn. Obstet Gynecol 2004;103:1229-34 Treatment of GDM Treatment of GDM Crowther et al. Effect of treatment of GDM on pregnancy outcomes. NEJM 2005;256:2277-86 Crowther et al. Effect of treatment of GDM on pregnancy outcomes. NEJM 2005;256:2277-86 3

6/9/2018 Treatment of GDM Goals of Glycemic Control  Blood glucose goals during pregnancy  Fasting < 95mg/dL  1-hr postprandial < 130-140mg/dL  2-hr postprandial am < 120mg/dL  2am < 120mg/dL Landon MB et al. NEJM 2009;361:1339-48 Question Question After one week of suboptimal blood sugars – 3/7 After three weeks of suboptimal blood sugars – 5/7 fasting values 95-110 and 4/7 post breakfast values post lunch values 140-150 and 3/7 post dinner values 140-150 what would you recommend? 140-150 what would you recommend? 44% 37% 36% A. Exercise and diet A. Exercise and diet 23% 23% B. Insulin B. Insulin 18% 15% C. Glyburide C. Glyburide 4% D. Metformin D. Metformin n n n n e t e e t e l i d m i l i d m i d i u r i d i u i s u r s u r r d n o d n o n I b f n I b f y t a y t a l e l e e G M e G M s s i i c c r r e e x x E E 4

6/9/2018 Treatment of GDM Treatment of GDM  Diet  Carbohydrate Controlled (not kcals)  Meals - 30-45 gms / 45-60 gms / 45-60 gms  Snacks – 15-30 gms  Exercise  Daily per routine  Also, 15 minute walks after each meal  Strategize – Behavioral Economics Adapted from ADA: Clinical Education Program “ Insulin Therapy for the 21 st Century ” Oral Agents Langer 2000: Insulin vs. Glyburide Langer et al. 2000  Glitazones - Decrease insulin resistance   Randomized controlled trial (n=404)  1st gen sulfonylureas - Augment insulin  Similar glycemic control  “ Similar ” neonatal outcomes release Neonatal Outcome Glyburide Insulin p-value  Concentrated in the neonate - hypoglycemia % (n) % (n)  Glyburide (2nd gen sulfonylurea) Birth weight > 4000 gms 7% (14) 4% (9) 0.26 Lung complications 8% (16) 6% (12) 0.43  Low transplacental transfer Hypoglycemia 9% (18) 6% (12) 0.25  Metformin – decreases insulin resistance Hyperbilirubinemia 6% (12) 4% (8) 0.36  Crosses placenta - Composite 30% 20% 0.05 Langer O et al. A comparison of glyburide and insulin in women with GDM. N Engl J Med 2000;242:1134-8 5

6/9/2018 Oral Agents vs. Insulin - CA Insulin vs. Oral Agents  Jacobson et al 2005 OR=1.35 Bwt >4kg  Retrospective cohort study (n=504) OR=0.51 OR=1.24 LGA >90% Neonatal Outcome Glyburide Insulin p-value OR=1.40 NICU % (n) % (n) Preeclampsia 12 % (28) 6 % (16) <0.05 OR=1.08 PTD <37w Birth wt > 4000 gms 24 % (63) 25 % (60) NS OR=1.52 PTD <34w Mean birth weight 3661 gms 3599 gms NS Birth injury 3 % (8) 1 % (3) 0.08 OR=2.19 IUFD Phototherapy 9 % (21) 5 % (12) <0.05 Adjusted Odds Ratio 0 0.5 1 1.5 2 2.5 3 Adjusted Odds Ratio Jacobson GF et al. Comparison of glyburide and insulin for the management of GDM. AJOG 2005;193:118-24 Multivariable logistic regression adjusting for maternal age, ethnicity, parity, education level, GA at delivery, GA at GDM diagnosis, BMI, and gestational weight gain – Cheng et al. AJOG, 2007 abs Oral Agents v. Insulin : Education < 9yrs Oral Agents v. Insulin : Spanish Language OR=1.48 Bwt >4kg OR=1.23 Bwt >4kg OR=0.51 OR=0.51 OR=1.47 LGA >90% OR=1.10 LGA >90% OR=2.06 OR=2.63 NICU NICU OR=1.19 OR=1.52 PTD <37w PTD <37w OR=1.66 OR=2.30 PTD <34w PTD <34w OR=0.49 OR=0.69 IUFD IUFD Adjusted Odds Ratio Adjusted Odds Ratio 0 0.5 1 1.5 2 2.5 3 0 1 2 3 4 5 Adjusted Odds Ratio Adjusted Odds Ratio Multivariable logistic regression adjusting for maternal age, ethnicity, parity, education level, GA at Multivariable logistic regression adjusting for maternal age, ethnicity, parity, education level, GA at delivery, GA at GDM diagnosis, BMI, and gestational weight gain - Cheng et al. AJOG, 2007 abs delivery, GA at GDM diagnosis, BMI, and gestational weight gain - Cheng et al. AJOG, 2007 abs 6

6/9/2018 Insulin v. Glyburide - Meta Insulin vs. Metformin  Rowan et al. NEJM, 2008  Prospective RCT – New Zealand / Australia  363 metformin vs. 370 insulin  46.3% of metformin pts required insulin  8.8% of pts had GI side effects – 1.9% stopped Balsells, BMJ, 2015 Insulin v. Metformin - Meta Insulin vs. Metformin Balsells, BMJ, 2015 Rowan et al. NEJM, 2008 7

6/9/2018 Insulin v. Metformin – Long Term Potential Management of GDM  Begin with diet / walk after each meal  If borderline/mild elevations, consider metformin (start 500 qd), or insulin  Counsel about increased PTD rates  Pt diagnosed in third trimester 26-32 wks  Unlikely pre-existing DM  Otherwise, or if metformin fails, insulin  Insulin NPH and humalog/novalog Rowan, BMJ Open, 2018 Medical Management of GDM - GDM ACOG PB - 2013 2010  ACOG Practice Bulletin:  No oral agents other than glyburide have been shown to be safe and effective in GDM  Further study recommended before use of newer oral hypoglycemic agents can be supported for use in pregnancy  Needs to be updated ACOG practice bulletin. Gestational Diabetes. Obstet Gynecol 2001;93:525-34 ACOG practice bulletin. Gestational Diabetes. Obstet Gynecol 2013 8

6/9/2018 Insulin v. Metformin - Meta Insulin v. Glyburide - Meta Balsells, BMJ, 2015 Balsells, BMJ, 2015 GDM SMFM - 2017 GDM ACOG PB - 2017 ACOG practice bulletin. Gestational Diabetes. Obstet Gynecol 2001;93:525-34 SMFM Am J Obstet Gynecol. 2018 9

6/9/2018 GDM ACOG PB - 2018 GDM ACOG PB - 2018 ACOG practice bulletin. Gestational Diabetes. Obstet Gynecol 2018 ACOG practice bulletin. Gestational Diabetes. Obstet Gynecol 2018 GDM ACOG PB - 2018 Diabetes and Pregnancy: Summary  Gestational Diabetes  Screening and Diagnosis  Universal screening  Management  Diet/exercise, nutritional consult  Self-monitoring of blood glucose  Insulin  Oral hypoglycemic agents controversial ACOG practice bulletin. Gestational Diabetes. Obstet Gynecol 2018 10

6/9/2018 Thank You Gestational Diabetes Mellitus  Insulin resistance first recognized during pregnancy Questions?  Prevalence: 1-14% of all pregnancies ACOG practice bulletin. Gestational Diabetes. Obstet Gynecol 2001;93:525-34 ADA position statement. Standards of Medical Care in Diabetes. Diabetes Care 2006;29:S4-42 GDM: Diabetogenic hormones GDM: β cell dysfunction? Human Placental Increased Insulin Lactogen β cell hypertrophy in first Response trimester Progesterone Insulin Resistance Inadequate Growth Hormone Block β cell hypertrophy Insulin Response Corticotropin- Releasing Hormone 11