Screening and Managing Diabetes in Pregnancy: “The Italian Model”

1. Screening and Managing Diabetes in Pregnancy: “The Italian Model” Battini L 1, Lacaria E 2, Trojano G 1, Bottone P 1, Fulceri M A 1, Carmignani A 1, Cattani R 1, Morini P 1, Salerno M G 1, Del Prato S 2, Di Cianni G 3, Bertolotto A 2. DepartmentObstretics-Gynaecology 2° Unit, University-Health Care System, Pisa, Italy 1; Universityof Pisa, DepartmentofEndocrinology and Metabolism, Pisa, Italy 2; Hospital of Livorno ASL6, DepartmentofDiabetes and MetabolicDiseases, Livorno, Italy 3.

2. Diabetes in Pregnancy Worldwide GDM Ww: 90% of DIP Up to 15% of all pregnancies GDM: 4 fold >risk of perinatal mortality Major cause of the 3 millions stillbirths ww A Leading Killer in the field of Obstetrics ! T1D Maternal mortality: 5-20 times higher vs normal pregnancy PPD without prec plan >highest risk maternal and neon mort/morbidity • Today as many as 60 million women of reproductive age have type 2 diabetes or GDM • In India alone, an estimated 4 million women have GDM. • These numbers are likely to increase as levels of maternal obesity continue to rise. International Diabetes Federation 2013

3. Diabetes in Pregnancy Pre-existing Diabetes (T1D, T2D, IGT) (2.5%) Gestational Diabetes (97.5%) Diabetes in Pregnancy Prevalence Italy/Europe: 6-7% 10% in Migrating Women ITALY: 1300/year ITALY: > 40.000/year DAWN Italy Survey

4. OptimizingOutcomes for Women withDiabetes in pregnancy Careful screening , diagnosis, metabolic management (Diabetologists/Dietists/Nurses) Appropriatelyappliedfetalsurveillancetechniques and maternal/obstetricmonitoring (Gynaecologists/Midwives) Thoughtfulselectionof the mostadvantageous timing and routeof delivery “ Multidisciplinary Expertise Team “ … Strategies Warning! Whenever possible, these clinical decisions should be based on the highest level of evidence available and should weigh the likelihood and seriousness of both maternal and fetal/neonatal morbidity

5. Diabetes causes life threatening complications in pregnancy To reduce maternal-fetalmorbidity/mortality Early Identification for Gestational Diabetes Careful pregnancy planning for pregestational diabetes

6. Diabetes causes life threatening complications in pregnancy EarlyIdentificationforGestationalDiabetes Carefulpregnancy planning forpregestationaldiabetes To reduce maternal-fetalmorbidity/mortality

7. RecommendationsforResearch MulticentricRandomizedControlledTrials are recommanded in ordertoassesefficacy and cost-effectivenessofdifferent Screening Procedures Italian Guidelines n.20, ISS CEVEAS SID AMD (sett 2011)

8. Background (1) Glucose load (g) Glucose tolerance test (mg/dl) Abnormal values for diagnosis Fasting 1 hour 2 hours 3 hours ADA 75 100 95 95 180180 155 155 140 2 or + 2 or + ADIPS 75 99 144 1 CDA 75 95 191 160 2 or + = GDM 1 = G-IGT WHO 75 126 200 1 Cheung NW: Vasc Health Risk Manag.2009 • Gestational diabetes mellitus (GDM) is one of the most common medical complications in pregnancy, affecting up to 15% of pregnant women (IDF) • Over the last 30 years, The GDM screening and diagnosis guidelines have not been uniform worldwide, with significant impact on maternal-fetal outcome ADA 2014 Guidelines

9. GestationalDiabetes: Screening and Diagnosis ADA 2014 Guidelines No uniform approach for GDM diagnosis Two options for women not previously diagnosed with overt diabetes: “One-Step” (IADPSG) • 75-g OGTT with PG measurement fasting and at 1h and 2h, At 24-28 weeks • Perform OGTT in am after overnight fast (≥8 h) • GDM diagnosis made if PG values equal or in excess of • Fasting: ≥92 mg/dl (5.1 mmol/L) • 1h: ≥180 mg/dl (10.0 mmol/L) • 2h: ≥153 mg/dl (8.5 mmol/L) “Two-Step” (NIH) • 50-g GLT (nonfasting) with PG measurement at 1h (Step 1), at 24-28 weeks • If PG at 1h after load is ≥140 mg/dl* (10.0 mmol/L), proceed to 100-g OGTT (Step 2), performed while patient is fasting • GDM diagnosis made when PG measured 3h post-test is ≥140 mg/dl* (7.8 mmol/L), *Threshold of 135 mg/dl in high-risk ethnic minorities with higher prevalence of GDM recommended by ACOG ACOG: American College of Obstetricians and Gynecologists; GLT: glucose load test; IADPSG: International Association of Diabetes and Pregnancy Study Group; NIH: National Institutes of Health; OGTT: oral gluose toloerance test; PG: plasma glucose American Diabetes Association, Diabetes Care. 2014;37 (suppl 1): S14-280

10. Background (2) • The HAPO study (Hyperglycemia and Adverse Pregnancy Outcome) in 1998, was designed to determine the association between non-diagnostic hyperglycemia and the risk of adverse pregnancy outcome. • Based on the HAPO study the “International Association of Diabetes and Pregnancy Study Groups" (IADPSG) Consensus Panel has formulated new criteria for the screening and diagnosis of GDM (Pasadena, June 2008) • The IADPSG criteria were (March 2010) adopted by the Italian Consensus Conference and applied in our Country IADPSG. Recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010.

11. GDM prevalence in Italy (Carpenter and Coustan Criteria) Universal Screening: 1h-CGT (50 g) ≥ 140 mg/dl  3h-OGTT (100 g) 5% – 8% Fasting≥95 mg/dl 1-hour ≥180 mg/dl 2-hours ≥155 mg/dl 3-hours ≥140 mg/dl Bonomo M et al. Diabet Med.2008 Lapolla A et al. Diabetes Nutr Metab. 2004

12. IADPSG Criteria Fasting plasma glucose at first prenatal visit: <92 mg/dl ≥ 92 mg/dl and < 126 mg/dl ≥126 mg/dl* 2h-OGTT (75 g) 24th-28th gestational weeks: Fasting <92 mg/dl ≥92 mg/dl 1-hour <180 mg/dl ≥180 mg/dl 2-hours <153 mg/dl ≥153 mg/dl Gestational Diabetes Overt Diabetes Normal glucose tolerance * Fasting plasma glucose ≥126 in at least 2 determinations or in 1 determination + 1 random plasma glucose ≥200

13. Aim of our study To evaluate the prevalence of GDM in a cohort of Italian pregnant women based on the IADPSG criteria. To compare these results with historical epidemiological data obtained in women living in the same area and with similar clinic characteristics

14. Subjects and methods (IADPSG Criteria) Screening pregnant women: Pisa – Leghorn University–Hospital , July 2010 – January 2011

15. Methods (IADPSG Criteria) Screening pregnant women: Pisa – Livorno, July 2010 – January 2011 Fasting plasma glucose at first prenatal visit: <92 mg/dl ≥ 92 mg/dl and < 126 mg/dl ≥126 mg/dl* 2h-OGTT (75 g) 24th-28th gestational weeks: Fasting <92 mg/dl ≥92 mg/dl 1-hour <180 mg/dl ≥180 mg/dl 2-hours <153 mg/dl ≥153 mg/dl Gestational Diabetes Overt Diabetes Normal glucose tolerance * Fasting plasma glucose ≥126 in at least 2 determinations or in 1 determination + 1 random plasma glucose ≥200

16. Methods (IADPSG Criteria) Screening pregnant women: Pisa – Livorno, July 2010 – January 2011 Fasting plasma glucose at first prenatal visit: <92 mg/dl ≥ 92 mg/dl and < 126 mg/dl ≥126 mg/dl* 2h-OGTT (75 g) 24th-28th gestational weeks: Fasting <92 mg/dl ≥92 mg/dl 1-hour <180 mg/dl ≥180 mg/dl 2-hours <153 mg/dl ≥153 mg/dl Gestational Diabetes Overt Diabetes Normal glucose tolerance * Fasting plasma glucose ≥126 in at least 2 determinations or in 1 determination + 1 random plasma glucose ≥200

17. Methods (IADPSG Criteria) Screening pregnant women: Pisa – Livorno, July 2010 – January 2011 Fasting plasma glucose at first prenatal visit: <92 mg/dl ≥ 92 mg/dl and < 126 mg/dl ≥126 mg/dl* 2h-OGTT (75 g) 24th-28th gestational weeks: Fasting <92 mg/dl ≥92 mg/dl 1-hour <180 mg/dl ≥180 mg/dl 2-hours <153 mg/dl ≥153 mg/dl Gestational Diabetes Overt Diabetes Normal glucose tolerance * Fasting plasma glucose ≥126 in at least 2 determinations or in 1 determination + 1 random plasma glucose ≥200

18. Methods (IADPSG Criteria) Screening pregnant women: Pisa – Livorno, July 2010 – January 2011 Fasting plasma glucose at first prenatal visit: <92 mg/dl ≥ 92 mg/dl and < 126 mg/dl ≥126 mg/dl* 2h-OGTT (75 g) 24th-28th gestational weeks: Fasting: <92 mg/dl ≥92 mg/dl 1-hour: <180 mg/dl ≥180 mg/dl 2-hours: <153 mg/dl ≥153 mg/dl Gestational Diabetes Overt Diabetes Normal glucose tolerance * Fasting plasma glucose ≥126 in at least 2 determinations or in 1 determination + 1 random plasma glucose ≥200

19. Clinical Characteristics

20. 642 18 < 92 mg/dl ≥ 92 mg/dl 2h-OGTT (75 g) 24th-28th week Results 660 pregnant women screened for GDM Fasting plasma glucose at first prenatal visit NGT 524 GDM 118 GDM 18 NGT: Normal glucose tolerance GDM: Gestational diabetes

21. Total GDM 136 (20.6%) GDM 118 (17.9%) GDM 18 (2.7%) GDM prevalence in the population studied Screening on 660 pregnant women Pisa – Livorno, July 2010 – January 2011 GDM diagnosed by 2h-OGTT (75 g) GDM diagnosed by FPG ≥ 92 mg/dl NGT: Normal glucose tolerance GDM: Gestational diabetes

22. Population of women with GDM Women with GDM (n. 136) 86,8 %

23. Risk Factors

24. Differences in RiskFactorsbetween GDM diagnosed in earlypregnancy and GDM diagnosedafter OGTT

25. Aim To evaluate GDM prevalence in a sample of Italian women a few months after the application of new guidelines. To compare these results with historical epidemiological data, obtained with old screening tests, in women living in the same area and with similar clinical characteristics

26. NGT 84.6% GDM 8.7% IGT 6.7% Historical GDM prevalence data based on Carpenter and Coustan Criteria G. Di Cianni et al., Prevalence and risk factors for gestational diabetes assessed by universal screening, Diabetes Research and Clinical Practice 62 (2003) 131-137 Screening 3950 pregnant women: Pisa, June 1995 – December 2001 NGT: Normal glucose tolerance IGT: Impaired glucose tolerance GDM: Gestational diabetes

27. OLD Criteria NEW Criteria Change in GDM prevalence INCREASE OF PREVALENCE + 136.8 % 20.6 % 8.7 % July 2010 – January 2011 June 1995 – December 2001 NGT: Normal glucose tolerance IGT: Impaired glucose tolerance GDM: Gestational diabetes

28. Change in the prevalence of all glucose tolerance abnormalities (GDM+IGT) OLD Criteria NEW Criteria INCREASE OF PREVALENCE + 33.8 % 15.4 % 20.6 % 8.7 % 6.7 % June 1995 – December 2001 July 2010 – January 2011 NGT: Normal glucose tolerance IGT: Impaired glucose tolerance GDM: Gestational diabetes

29. Italian Health Ministry Criteria (September 2011) … the evolution of screening

30. GDM Screening in Pregnant Women withriskfactors: New ItalianHealthMinistryGuidelinesApplication • Toevaluate National Guidelines (NGL )application • To estimate GDM incidence in the differentrisklevelpregnancies … the evolution of our study… Aim of the study

31. Study population • A 2552 cohort of caucasian pregnant women (Tab.2) screened by OGTT ( FPG, 2hs curve, 75g. ) at 2 Univ-Hosp. Diabetes Centers Tuscany Pisa, Leghorn-Italy)

32. Study population: risk factors stratification

33. Results

34. Results: GDM n. 279 (10.9%) NTG GDM Low Risk Medium Risk High Risk

35. Screening Conclusions • Our data, although preliminary, shows that adoption of the IADPSG diagnostic criteria, as compared to our historical data, is associated with a greater prevalence of gestational diabetes ( +136.8 %) • However, if all abnormalities of glucose tolerance are considered, the performance of the old and new criteria are less apparent and more similar. ( +33.8%) • The impact of diagnosis determined by fasting plasma glucose detected in early pregnancy was significant ( 13.2%) • The INGL are not yet correctly applied, particularly in HR women who undergo late to OGTT and delay diagnosis with risk of impaired maternal fetal outcome • Further studies are needed to assess whether this increasing diagnostic accuracy is more effective in terms of cost-benefit analysis.

36. 1750 PW screened by CC (from Apr 2011 to March 2012)vs 1526 PW screened by IADPSG ( from Apr 2012 to March 2013) • The use of the new IADPSG Criteria for diagnosis of GDM results in an incresed prevalence of GDM (35,5% vs 10,6%) • An improvement in pregnancy outcomes: gestational hipertension (4,1 vs 3,5%: -14,6%. P<0,021) Prematurity (6,4 vs 5,7%: -10,9%. P<0,039) Cesarian section (25,4 vs 19,7%: -23,9%. P<0,002) SGA (7,7 vs 7,1%: -6,5%. P<0,042) LGA (4,6 vs 3,7%: -20 %. P<0,004) Apgar 1-min score <7 (3,8 vs 3,5%: -9 %. P<0,015) Admission to NICU (8,2 vs 6,2%: -24,4%. P<0,001) • Estimated cost savings (IADPSG vs CC: €14358,06 per 100 women

37. GestationalDiabetesRecommendations ADA 2014 Guidelines American Diabetes Association, Diabetes Care. 2014;37 (suppl 1): S14-280

38. Educational Therapy: what we do ! Women coming for OGTT Screening are collected for ET chair in which informations regarding GDM and its prevention are given 2 Steps EDUCATIONAL THERAPY : • collective (to all screened women) • personalized (only for GDM screen positive women)

39. Informations recommended for women affected by Gestational Diabetes (GDM) (1) • In most of women GDM is controlled by diet and physical activity modification and checked by SMBG, medically revised every 7-15 days till authonomy • If these modifications are insufficient to maintain glycemia in the expected target: < 92 ( <95, ADA 2014) at fasting and < 130 ( <140, ADA 2014), 1 hour after eating, insulin therapy is recommended; This condition occurs in about 10-20% of GDM complicated pregnancies • If GDM is not controlled, a significant increase of pregnacy complications, like preeclampsia and shoulder dystocia, may occur . • Gestational Diabetes diagnosis is often associated to a potential increase in monitoring and caring procedures during pregnancy and delivery IGL n.20, sept.2011, ADA GL 2014

40. Informations recommended for women affected by Gestational Diabetes (GDM) (2) • Women affected by GDM are at increased risk of developing Tipe 2 Diabetes, particularly in the 5 years following delivery • Women diagnosed with GDM, need to be checked by follow up OGTT ( 2 determinations : basal and 120’ after 75 g oral glucose loading), at least 6 weeks after delivery. Normal values : Fasting glycemia <110 mg/dl 120’ after oral glucose load < 140 mg/dl TEST NEGATIVE WOMEN continue to screen at least every 3 years TEST POSITIVE WOMEN: lifestyle interventions and/or Metformin for diabetes prevention IGT Women : screeneveryyear IGL n.20, sept.2011, ADA GL 2014

41. OptimizingOutcomes for Women withDiabetes in pregnancy Careful screening , diagnosis, metabolic management (Diabetologists/Dietists/Nurses) Appropriatelyappliedfetalsurveillancetechniques and maternalobstetricmonitoring (Gynaecologists/Midwives) Thoughtfulselectionof the mostadvantageous timing and routeof delivery “Multidisciplinary Expertise Team”… Strategies Warning! Whenever possible, these clinical decisions should be based on the highest level of evidence available and should weigh the likelihood and seriousness of both maternal and fetal/neonatal morbidity

42. (IGL n.20, sept.2011) GDM Obstetric Prenatal Monitoring

43. Fetal Surveillance All women with Diabetes in Pregnancy should monitor fetal movements during the last 8–10 weeks of pregnancy and report immediately any reduction in the perception of fetal movements WARNING !!! ACOG Practice Bulletin 2001

44. GDM Fetal Surveillance Conway D.L.,Obstetric Management in Gestational Diabetes, Diabetes Care 30:S175-S179, 2007, by ADA

45. Pre-existingDiabetes IGL 2011 - CDA, Clinical Practice Guidelines, 2013 (Further incresad monitoring rate, only if necessary)

46. Timing and Mode of Delivery (1) (IGL n.20, sept.2011)

47. Time and Route of Delivery (2) IGL 2011, ADA 2004, NICE 2008, CDA 2013

48. Diabetes causes life threatening complications in pregnancy EarlyIdentificationforGestationalDiabetes Carefulpregnancy planning forpregestationaldiabetes To reduce maternal-fetalmorbidity/mortality IGL n.20, 2011 IDF, 2013

49. Preconception Family Planning! Preexisting Diabetes Mellitus Type 1 DM Impaired Glucose Tolerance (IFG,IGT) Type 2 DM Worldwide, only 10% of diabetes in pregnancy is pregestational

50. Preconception Family Planning to reduce risk in PrePregnancyDiabetic Women To offer the Baby and the Mother the best chance for Life and Health Promotion by significantly decreasing • abortion • malformations • macrosomia and its complications • preeclampsia • perinatal death …and to shift From Eugenetics ... to the Ethic of Prevention ADA, Official Position, 2003