1. UPDATE ON GESTATIONAL DIABETES: CONTROVERSIES, CHANGES AND CHALLENGES JAMES R. SCOTT, MD I HAVE NO CONFLICT OF INTEREST TO DISCLOSE

2. OBJECTIVES TO DEFINE GESTATIONAL DIABETES, ITS PREVALENCE AND DIAGNOSIS TO RECOGNIZE THE COMPLICATIONS FOR MOTHER AND BABY TO APPLY THE FINDINGS OF THE NIH CONFERENCE TO YOUR PATIENTS

3. DEFINITIONS TYPE 1 DIABETES (JUVENILE, INSULIN DEPENDENT) COMPLETE FAILURE OF PANCREAS TO SECRETE INSULIN TYPE 2 DIABETES (ADULT ONSET) INSULIN SECRETORY DEFICIENCY & INSULIN RESISTANCE IN VARIOUS ORGANS GESTATIONAL DIABETES (GDM, PRE-DIABETES) FIRST RECOGNIZED DURING PREGNANCY PREGNANCY HORMONES  CARBOHYDRATE INTOLERANCE

4. THE PROBLEM DIABETES ASSOCIATED WITH OBESITY 1/3rd OF AMERICANS OBESE & INCREASING 11% OF ADULT AMERICANS HAVE DIABETES 35 % HAVE PREDIABETES Total = ALMOST HALF THE POPULATION PREVALENCE INCREASING & AT YOUNGER AGE GDM COMMON COMPLICATION - 6-7 % OF PREGNANCIES US COST - $635 MILLION ANNUALLY

5. BOISE 27.9% 22.2 – 34.2

7. SCREENING TEST FOR GDM DIAGNOSIS CRITERIA ESTABLISHED 30-40 YEARS AGO TO IDENTIFY WOMEN AT RISK OF DEVELOPING DIABETES LATER IN LIFE 50% DEVELOP DIABETES IN 22-28 YEARS BASED ON NON-PREGNANT WOMEN NOT TO IDENTIFY RISK OF ADVERSE PREGNANCY OUTCOME

8. Universal vs targeted screening debated US: Most screen all pregnant women US Preventive Health Service does not recommend screening (2008) “Current evidence is insufficient to assess the balance between the benefits and harms of screening women for GDM either before or after 24 wks. Harms of screening include short-term anxiety…and inconvenience to women and medical practices because most positive screening tests are likely false positives.” GDM SCREENING CONTROVERSIES

9. CURRENTLY, ALL PREGNANT WOMEN TESTED FOR GDM AT 24-28 WEEKS SOME TEST WOMEN AT HIGH RISK FOR GDM (AND ALL TYPE 1 DIABETICS SHOULD BE) AT FIRST PRENATAL VISIT 50 GM GLUCOSE SCREEN > 140 mg/dl HbA1C GDM > 6.5 (Has not been validated)

10. AT RISK FOR GDM OLDER THAN AGE 25 OVERWEIGHT HAD GDM BEFORE HAD VERY LARGE BABY CLOSE RELATIVE WITH DIABETES PREVIOUS STILLBIRTH AFRICAN AMERICAN, INDIAN, HISPANIC

11. U.S. GDM SCREENING/DIAGNOSIS TWO - STEP TESTING 1 hr 50 gm oral glucose load @ 24-28 wks If >140 mg/dl  3 hr 100 gm oral glucose load [> 2 values] Fasting 105 mg/dl 1 hr 190 mg/dl 2 hr165 mg/dl 3 hr145 mg/dl

12. Distribution of Blood Sugars in Pregnancy Blood glucose Overt DM Gestational DM

13. GDM COMPLICATIONS PREECLAMPSIA MACROSOMIA SHOULDER DYSTOCIA, BIRTH INJURY CESAREAN DELIVERY NEONATAL Hyperbilirubinemia Hypoglycemia Respiratory Distress Syndrome

14. PRIOR TO 2005, NO EVIDENCE THAT TREATMENT OF GDM IMPROVED MATERNAL OR INFANT OUTCOME Macrosomia/LGA Shoulder Dystocia

15. NEW DATA DEMONSTRATED HYPERGLYCEMIA IS A CONTINUUM 2008 HAPO Study: 25,505 women Continuous association between glucose levels and adverse pregnancy outcomes Increasing fasting, 1 and 2 hr glucose  glucose Birth weight >90%tile No clear cut-point

16. Criteria based on pregnancy outcomes Cut-offs defined from adverse outcomes Most of world uses 2hr 75 gm OGTT Endorsed by American Diabetes Association NEW CRITERIA FOR DIAGNOSING GDM PROPOSED

17. LOWER THRESHOLDS Recommended IADPS thresholds correspond to 1.75-fold risk for large and/or “hyperinsulinemic” infants 70 – 80% of overgrown infants born to women without diabetes Metzger et al NEJM 2008

18. SINGLE STEP 75 g 2 hr OGTT - One abnormal value for GDM diagnosis: Fasting 92 mg/dl 1 hr180 mg/dl 2hr153 mg/dl Lowers thresholds  more women diagnosed as GDM

19. Blood glucose Increased Prevalence ~ 18% Overt DM Gestational DM New Gestational DM

20. MAY BE EVEN HIGHER GDM tripled from 10.3% to 30.1% using IADPSG thresholds. Reyes-Munoz et al Endocrine Practice 2012 GDM rate increased to 27.5 % Bodmer-Roy et al Obstet Gynecol 2012

22. Rationale for Consensus Conference To Address this complicated issue To clarify diagnostic thresholds Rigorous evaluation of existing evidence Implications of new proposed thresholds Develop Recommendations

24. Produce consensus statements on important, controversial topics in medicine Began in 1977 Goal: evaluate available scientific information and develop a statement that advances understanding of the issue useful to health professionals and the public at large http://prevention.nih.gov/cdp/about.aspx

25. Process: Independent systematic review by AHRQ Evidence-based Practice Center Provided to panel 6 wks prior to conference Conference 2.5 days of expert presentations and open public discussion Panel drafts statement for presentation on 3 rd day

26. Consensus Conference Panelists: Knowledgeable about topic but have no published or known opinion on subject No financial or career interest in topic Represent a variety of perspectives “independent assessment of available knowledge”

27. CHARGE – EVALUATE EVIDENCE AND IMPLICATIONS IF NEW GDM SCREENING PROPOSAL INSTITUTED 1.Evidence that additional patients identified have increased frequency of maternal/ perinatal morbidities 2.Evidence that these morbidities can be prevented or decreased by intervention 3.Evidence that benefits outweigh harms incurred

28. Potential Benefits

29. ACCEPTED WOULD HAVE UNIFORM WORLDWIDE SCREENING SYSTEM BASED ON PREGNANCY OUTCOMES CUT-OFFS BASED ON ADVERSE EVENTS ABLE TO COMPARE RESEARCH & CLINICAL OUTCOMES

30. HAPO STUDY Showed increased maternal and perinatal risks at thresholds lower than currently used, but….. Maternal BMI and weight gain major confounders Metzger et al NEJM 2008

31. ACHOIS RCT ON Rx vs No Rx Reduced preeclampsia from 18% to 12% Reduced LGA from 22% to 13% Reduced birth wt > 4000 gm from 21% to 13% Crowther et al. NEJM 2005

32. MFM NETWORK RCT ON Rx vs NO Rx Reduced LGA from 14.5% to 7.1% Reduced shoulder dystocia from 18% to 7% Reduced birth trauma from 1.3% to 0.6% Reduced neonatal composite score (37 to 32) No stillbirths in either group Rate of cesarean same in both groups Landon et al NEJM 2009

33. CAUTION IN INTERPRETATION 1.Trial participants highly motivated - ? Generalizable to practice 2.Not all treatments were same (not studied) 3.Different thresholds for criteria to diagnose GDM

34. CONCLUSIONS GDM Risks present but mild and relatively low even without Rx Maternal Rx reduces some maternal and infant adverse outcomes Overall reduction in adverse events relatively small

35. Potential Harms

36. PROBLEMS IN REAL WORLD PATIENTS MEDICALIZATION OF PREGNANCY INCONVENIENCE – MUST SCHEDULE OGTT (REQUIRES FASTING) FOR ALL OB PATIENTS MONITORING OF GLUCOSE MORE VISITS, TRAVEL, TIME, BABYSITTERS EMOTIONAL IMPACT

37. IMPLICATIONS FOR PROVIDERS MANPOWER – MORE PERSONNEL NEEDED FOR 30% INCREASED WORKLOAD MORE EDUCATION VISITS, CLINIC VISITS, TESTING VISITS MORE ULTRASOUNDS, NSTs AND OTHER MONITORING MORE INDUCTONS PROBABLY MORE CESEAREAN DELIVERIES HIGHER RATES OF NBICU ADMISSIONS

38. IMPLICATIONS FOR U.S. HEALTH CARE SYSTEM INSTITUTING CHANGE SIGNIFICANT IMPACT ON CAPACITY DRAMATIC INCREASE IN WOMEN WITH MILDER GDM DIAGNOSIS WILL LEAD TO SIGNIFICANT HEALTH CARE COSTS

39. Annual Cost of Gestational Diabetes Status Quo $2 Billion $636 Million IADPSG Chen et al, Population Health Management, 2009

40. No evidence that identification and treatment of this new large group of “Borderline GDM” women is beneficial Improvement in short-term outcomes in women with mild GDM less likely MOST IMPORTANT

41. CONCLUSION Not sufficient evidence to adopt one-step approach Would increase prevalence of GDM, costs, and interventions without improvements in most clinically important patient outcomes Given potential benefits of one-step approach, further research and reconsideration warranted

42. Panel supports maintaining current U.S. diagnostic approach for gestational diabetes mellitus http://www.nih.gov/news/health/mar2013/o d-06.htm

43. BOTTOM LINE: Disadvantages outweigh advantages Keep present two-step approach Screen with 1 hr OGTT followed by 3 hr OGTT prn

44. MY PERSPECTIVE NIH CONFERENCE GOT IT RIGHT DON’T OVERDIAGNOSE OR OVERTREAT GESTATIONAL DIABETES OBESITY BIGGER PROBLEM AND DIFFICULT TO MANAGE TYPE 1 DIABETES MUCH MORE SERIOUS FOR MOTHER AND BABY – NEED EXPERT CARE AND “WATCH HER LIKE A HAWK”

45. REFERENCES 1.VanDorsten JP, DODSON W, Espeland MA et al. Diagnosing gestational diabetes mellitus. NIH Consensus Development Conference Statement. NIH Consens State Sci Statements 2013;29(1):1-30. Available at: http://prevention.nih.gov/cdp/conference/2013/gdm/files/Gestional_ Diabetes_Mellitus.508.pdf http://prevention.nih.gov/cdp/conference/2013/gdm/files/Gestional_ Diabetes_Mellitus.508.pdf 2.Gestational Diabetes Mellitus. ACOG Practice Bulletin 2013;137:1-11. 3.Crowther CA, Hiller JE, Moss JR et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. Australian Carbohydrate Intolerance study (ACHOIS) Trial Group. N Engl J Med 2005;352:2477-86 4.Metzger BE, Lowe LP, Dyer AR et al. Hyperglycemia and adverse pregnancy outcomes. HAPO Study Cooperative Research Group. N Engl J Med 2008;358:1991-2002. 5.Landon MB, Spong CY, Thom E et al. A multicenter, randomized trial of treatment for mild gestational diabetes. Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network. N Engl J Med 2009;361;1339-48 6.Metzger BE, Gabbe SG, Person B et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. International Association of Diabetes and Pregnancy Study Groups Consensus Panel. Diabetes Care 2010;33;676-82.