Gestational Diabetes

1. Gestational Diabetes Bashir Taha Salih MD Germany,FRCOG UK Consultant & ChiefObstetric Medicine Corniche Hospital Abu Dhabi Kuwait April 27th 2014

2. Contents • Introduction • Physiology What’s new in GDM ? • In Screening • In Management • Conclusion

3. Introduction GDM increases the risk of complications for both mother and fetus during pregnancy, childbirth and beyond – increased risk of Type 2 diabetes International Association of Diabetes and Pregnancy Study Groups, Diabetes Care March 2010 vol. 33 no. 3 676-682

4. Introduction Current evidence suggests early detection and management of gestational diabetes: • Improves outcomes for both mother and baby • More cost effective by preventing the complications International Association of Diabetes and Pregnancy Study Groups, Diabetes Care March 2010 vol. 33 no. 3 676-682 National Collaborating Centre for Women's and Children's Health. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the Postnatal Period. London, U.K., RCOG Press, 2008

5. Definition Gestational Diabetes Mellitus (GDM) is one of the most common medical disorders in pregnancy and is defined as “any degree of glucose intolerance with onset or first recognition during pregnancy” American Diabetes Association. Diagnosis and classification of diabetes mellitus (Position Statement). Diabetes Care 2009;32(Suppl. 1):S62–S67

6. Diabetes in pregnancy and risk of complications Dunne et al. Diabetes Care 2009;32:1205–6 • Pre-existing diabetes in pregnancy is associated with high rates of complications: • Fetal/neonatal • Congenital malformations • Perinatal mortality • Excess fetal growth • Traumatic delivery • Neonatal hypoglycaemia • Hyperbilirubinaemia • Diabetic fetopathy • Maternal • Pregnancy-induced hypertension/pre-eclampsia • Polyhydramnios/large for gestational age • Operative delivery

7. Diabetes in pregnancy and risk of complications Confidential Enquiry into Maternal and Child Health (CEMACH): Pregnancy in Women with Type 1 and Type 2 Diabetes in 2002–03, England, Wales and Northern Ireland. London: CEMACH; 2005

8. Blood glucose control is linked with outcomes in diabetic pregnancy Diabetes Control and Complications Trial. Am J Obstet Gynecol 1996;174(4):1343–53

9. Glycaemic thresholds for prevention of diabetic fetopathy complications? LGA, large for gestational age Langer. Diabetes Reviews 1996;4:2–10

10. Diabetes in Pregnancy Pre-existing diabetes Gestational diabetes Pre-existing (overt Diabetes) DM type 1 True GDM DM type 2 Classification of Diabetes in Pregnancy

11. Physiology of  Insulin resistance during pregnancy Increased insulin resistance is : the decreased biological response to given concentration of insulin at the target tissues, such as liver, muscle, or adipose tissue. Insulin resistance is implicated in (T2D) & (GDM) pathophysiology Strongly linked with metabolic syndrome and associated with increased risk of developing cardiovascular diseases (CVD) Over the course of normal pregnancy, insulin sensitivity decreases by 50 %–60 % . Level of insulin resistance achieved in late pregnancy comparable to the level observed in patients with impaired glucose tolerance (IGT) or newly diagnosed with T2D .

12. Physiology of  Insulin resistance during pregnancy GDM results from an imbalance between increased insulin resistance and the capacity of pancreatic β-cells to face the demand increasing through pregnancy. Some of the mechanisms raising insulin resistance are likely the same during and outside of pregnancy, while other pathways are probably specific to gestational physiologic adaptations and hormonal regulation

13. Physiology of  Insulin resistance during pregnancy Cytokines and Adipokines The adipose tissue is now recognized as an endocrine organ that is capable of producing a significant amount of cytokines and hormones, often called adipokines. In non-pregnant populations, many cytokines and Adipokines, including TNFα, Leptin, and Adiponectin, have been suspected to contribute to insulin resistance pathways . Interestingly, the placenta seems also to be a significant source of ‘classic’ Adipokines such as Leptin and of proinflammatory cytokines (TNFα, Interleukins, etc).

14. Physiology of  Insulin resistance during pregnancy They found that TNFα showed the strongest correlation with insulin sensitivity, both in early and late pregnancy and that most of the placental production of TNFα was released on the maternal side towards the maternal circulation. None of the pregnancy-related hormones were significantly associated with insulin sensitivity, but Leptin was the second best predictor among the circulating protein assessed in this specific sample of women

15. Physiology of  Insulin resistance during pregnancy • Maternal/Fetal Determinants of Insulin Resistance in Women During Pregnancy and in Offspring Over Life by Marilyn Lacroix & Eralda Kina & Marie-France Hivert Published online: 11 January 2013 LEPTIN: Initially described as an adipokine responsible for energy balance Leptin level increases early in pregnancy, reaches a peak in the second trimester, remains stable in late pregnancy, and falls within hours after delivery .Suggesting that the placenta contributes to a significant portion of circulating levels during pregnancy. In GDM women, expression of LEP has been shown to be higher in adipose tissue and in the placenta .

16. Maternal and Early Determinants of Insulin Resistance in Offspring • Maternal/Fetal Determinants of Insulin Resistance in Women During Pregnancy and in Offspring Over Life by Marilyn Lacroix & Eralda Kina & Marie-France Hivert Published online: 11 January 2013 Maternal Obesity was associated with insulin resistance in young adults . At birth, higher maternal (BMI) is associated with higher cord blood insulinemia, even in women with normal glucose tolerance or independently of maternal glycemia It is also possible that obese women that are ‘normoglycemic’ have ‘relative’ hyperglycemia leading to some degree of fetal hyperinsulinemia and its consequences.

17. Maternal and Early Determinants of Insulin Resistance in Offspring • Maternal/Fetal Determinants of Insulin Resistance in Women During Pregnancy and in Offspring Over Life by Marilyn Lacroix & Eralda Kina & Marie-France HivertPublished online: 11 January 2013 Birth Weight associated with increased risk of insulin resistance at both ends of the spectrum: being small for gestational age (SGA) or large for gestational age (LGA) was associated with higher HOMA-IR compared with children who were appropriate for gestational age (AGA) at birth Correlation between SGA and increase insulin resistance was confirmed in numerous studies, including young adults that were assessed by the intravenous minimal model method or the euglycemic hyperinsulinemic clamps suggested that abnormal adipose tissue metabolism is part of the pathophysiological processes linking low birth weight to insulin resistance.

18. In Summary : • Maternal/Fetal Determinants of Insulin Resistance in Women During Pregnancy and in Offspring Over Life by Marilyn Lacroix & Eralda Kina & Marie-France Hivert Published online: 11 January 2013 One of the determinants of insulin resistance in normal pregnancy and GDM is placenta which is capable of secreting many cytokines and hormones, classically considered as adipocytes. More specifically, it appears that leptin and TNFα could be implicated in gestational insulin resistance and GDM pathophysiology. Overall, pregnancy-related increase in insulin resistance helps to reveal a defect in insulin action and/or insulin secretion compensatory capacity. For this reason, pregnancy is often considered ‘a window’ to identify women at risk of developing T2D in the future and an opportunity for prevention. In addition, the maternal metabolic milieu was also identified as a key determinant of later insulin resistance in offspring, a phenomenon often described as ‘fetal programming’

19. Screening of Gestational Diabetes Who to Screen? Screen all pregnant women!

20. Universal VS Selective Screening • At present, both methods are employed in reputable centers • In UAE as the prevalence of diabetes is high, universal screening is recommended • Selective screening has a sensitivity of 63% and a specificity of 56% • In other words, 37%–50% of women with GDM may go undiagnosed using this approach

21. Prevalence of DiabetesTop Ten Countries/Territories http://www.idf.org/sites/default/files/da5/prevalence IDF Diabetes Atlas 2011

22. When to Screen ? • At booking • Earlier the screen the better the outcome • First prenatal visit: Test for overt diabetes • At 24-28 weeks IADSPG

23. GUIDELINES

24. GDM Diagnosis Controversy Difference in 6 major criteria for GDM diagnosis? • WHO (World) • EASD (European) • ADA (American) • CDA (Canadian) • ADIPS (Australasian) • NZSSD (New Zealand) Agarwal et al. Diabetic Medicine 2005

25. Guidelines

26. Hyperglycemia and Adverse Pregnancy Outcome Study

27. HAPO Trial • Hyperglycemia & adverse pregnancy outcome • Randomized Clinical Trial • 15 world centers • 25,000 women • Six years • Aims to correlate various levels of glucose to outcome

28. The HAPO Study The HAPO Study was designed to clarify unanswered questions on associations of maternal glycaemia, less severe than overt diabetes mellitus, with risks of adverse pregnancy outcome.

29. The HAPO Study • Primary outcomes in the blinded HAPO cohort • Birth weight >90th percentile • Primary cesarean section delivery • Clinically defined neonatal hypoglycemia • Cord C-peptide >90th percentile

30. The HAPO Study • Secondary outcomes • Pre-eclampsia • Preterm delivery • Shoulder dystocia/birth injury • Hyperbilirubinemia • Intensive neonatal care

31. The HAPO Study Frequency of primary outcomes across the Glucose categories The HAPO Study Cooperative Research Group. N Engl J Med

32. The HAPO Study • Results indicate strong associations of maternal glucose levels below those diagnostic of diabetes with adverse pregnancy outcomes.

33. International Association of Diabetes and Pregnancy Study Groups (IADPSG) Formed in 1998 as an umbrella organization to facilitate collaboration between the various regional and national groups that have a primary or significant focus on diabetes and pregnancy.

34. Objectives of IADPSG • Foster an international approach to enhancing the quality of care • Facilitating research • Advancing education in the field of diabetes in pregnancy.

35. International Council Diabetes in Pregnancy Groups • European • Japanese • Australasian • Canadian • USA • India • ADA Diabetes Care March 2010

36. IADPSG CRITERIA

37. UNIVERSAL SCREENING FOR DIABETES MELLITUS IN PREGNANCY At booking:- FBS+ HbA1C + RBS FBS >7.0 mmol/l Or HbA1c > 6.5% or RBS >11.1mmol/l If :FBS < 5.1 mmol/l HbA1c < 6.5% RBS < 11.1mmol/l If FBS >5.1mmol/l And < 7.0mmol/l GDM , no further test Overt diabetes No further test 75 gm OGTT at 24-28 wks Threshold : FBS: 5.1mmol/l 1 Hr : 10.0 mmol/l 2 Hrs : 8.5 mmol/l Dietician (medical nutrition Therapy) CDC/ DE (Insulin+Met) Normal diet + BSS HbA1c 4 wkly GDM: 1or more values ≥ threshold Normal Low risk Abnormal

38. IADPSG • If results indicate overt diabetes Treatment and follow-up as for pre-existing diabetes

39. IADPSG If results not diagnostic of overt diabetes and Fasting plasma glucose ≥ 5.1 mmol/L (92 mg/dl) but < 7.0mmol/l(126 mg/dl) “Treat as Gestational Diabetes (IADPSG)”

40. What to do? If FPG is < 5.1 mmol/L (92 mg/dL)

41. The Glucose Tolerance Test

42. Timing of OGTT • At 24-28 weeks of pregnancy as per IADPSG criteria. • Insufficient data to recommend OGTT to diagnose Overt diabetes prior to 24-28 weeks.

43. IADPSG- Detection & Diagnosis of Hyperglycemia Disorders in Pregnancy • First Antenatal Visit: Test for overt DM • FBS,HbA1C or RBS in all women • Results indicate overt DM • Treatment & follow up as for pre-existing DM • Results not diagnostic of overt DM • FBS 5.1-6.9mmol/l = GDM • Others: test for GDM 24-28 weeks gestation with 75g OGTT

44. IADPSG - Adoption Of Criteria

45. UPSTF All women should be screened for gestational diabetes at 24 weeks of pregnancy, even if they have no symptoms, according to new federal recommendations. The B-level recommendation from the U.S. Preventive Services Task Force (USPSTF), published in the Annals of Internal Medicine, aligns with that of several other medical organizations, including the American Association of Clinical Endocrinologists, American Diabetes Association (ADA), and the American College of Obstetricians and Gynecologists (ACOG).

46. Audit of Universal Screening of Diabetes in Pregnancy using IADSP in Corniche Hospital

47. Obstetric Medicine in Corniche Hospital • Corniche Hospital is a 235 bedded largest maternity tertiary hospital in the UAE with 8,000 to 10,000 deliveries per annum. • The Obstetric medicine department was established in 1994. • Provides daily inpatient and out patient consultation for women with medical problems predating, during or after pregnancy. • The only unit outside UK accredited to train Obstetrians in Maternal medicine by the RCOG • Provides 24/7 on call service.

48. Results

49. Conclusion • Higher incidence of GDM - 36% • 21% had no risk factors • This is a higher detection rate than that reported in countries where IADPSG Criteria where applied

50. Why is it important to treat Diabetes in Pregnancy?