Diabetes and Pregnancy

1. Diabetes and Pregnancy Dr Khalid Akkour MD. FRCSC Asst. Professor & Consultant Gynecologic Oncologist

2. Two Types: • Preexisting DM and pregnancy • Gestational diabetes

3. Diabetes in pregnancy Pre-existing diabetes Gestational diabetes IDDM (Type1) NIDDM (Type2) Pre-existing diabetes True GDM

4. Preexisting diabetes in pregnancy • Type 1 DM ( IDDM) • Type 2 DM (NIDDM)

5. Preexisting DM in pregnancy Effect of pregnancy on pre-existing DM • Increase requirement for insulin doses • Nephropathy , autonomic neuropathy may deteriorate • Progress in diabetic retinopathy (2X) • Hypoglycemia • Diabetic ketoacidosis

6. Preexisting DM In Pregnancy Effect of preexisting DM on pregnancy • Maternal 1. increase risk of miscarriage 2. increase risk of preclampsia 3. increase risk of infection eg vaginal candidiasis, UTI, endometrial or wound infection 4. increase LSCS rate

7. Preexisting DM in Pregnancy (2) Fetal 1. increase risk of congenital abnormalities sacral agenesis, congenital heart disease, neural tube defects Hba1c levelRisk normal not increased <8% 5% >10% 25 %

8. Preexisting DM in Pregnancy 2. Perinatal mortality (excluding congenital abnormality ) 2 fold increased 3. Increase risk of sudden unexplained intrauterine fetal death.

9. Complications of pregnancy in pre-existing DM Maternal: Increase insulin requirment’ Hypoglycemia Infection Ketoacidosis Deterioration in retinopathy’ Increased proteinuria+edema Miscarriage Polyhydramnios Shoulder dystocia Preeclampsia Increased caesarean rate Fetal: Congenital abnormalities Increased neonatal and perinatal mortality Macrosomia Late stillbirth Neonatal hypoglycemia Polycythemia jaundice

10. Maternal hyperglycemia | Fetal hyperglycemia | Fetal pancreatic beta-cell hyperplasia | Fetal hyperinsulinaemia | Macrosomia,organomegaly, polycythaemia, hypoglycemia, RDS

11. Management Aim Achieve maternal near normoglycemic level to prevent adverse perinatal outcomes

12. Diet • Low-carbohydrate diet , high fibre with caloric restriction • Frequent small snacks may be needed between meals • Avoid starvation

13. Insulin • 3 pre-meal short acting insulin (actrapid) +/- intermediate-acting insulin (protophane) as it allows maximum flexibility • Target blood glucose: fasting < 5mmol/L 2 hr <7 mmol/L

14. Oral Hypoglycemic agents • Implicated as teratogeneic in animal studies esp first generation sulfonyureas • In humans, scattered case reports of congenital abnormality • Risk of congenital abnormality related to maternal glycemic control rather than mode of the anti-DM agents

15. Oral hypoglycemic agents • For Type 2 DM patients, to stop oral hypoglycemic agents and change to insulin Reassure that the risk of congenital abnormality due to oral hypoglycemic agents is very small

16. Oral hypoglycemic agents • Biguanides ( metformin) • Cat B drug • Commonly used in Polycystic Ovarian Disease (PCOD) to treat insulin resistance and normalize reproductive function • Not teratogeneic • Reduce first trimester miscarriage • 10X reduce gestational diabetes Glueck, Fertil Steril 2002 Reece, Curr Opin Endocrinol Diabetes, 2006 Hague, BMJ, 2003 Glueck, Human Reprod, 2004

17. Oral hypoglycemic agents Sulfonylureas • 1st generation drug increase risk of neonatal hypoglycemia • 2nd generation drug (Glyburide) no such effect and other morbidities . • Cat C drug • 4%-20% patients failed to achieve glucose control with maximum dose of drug • Increase risk of preeclampsia and need for phototherapy Langer, N Eng Med J , 2000 Kremer, Am J Obst Gynaecol, 2004 Chmait, J Perinatol ,2004 Langer, Am J Obst Gynaecol, 2005

18. Insulin Analogues • 1. rapid-acting insulin analogs (lispro) Cat B concerns about teratogenesis, antibodies formation, growth-promoting properties majority of evidence showed that it does not cross placenta, and has no adverse maternal or fetal effects

19. Insulin Analogues 2. Long acting analogs glargine Cat C drug Not well studied systemically

20. Monitoring • Regular home glucose monitoring • Insulin may be need to be adjusted as gestation advances • Hba1c monitoring • Fetal monitoring with USG • Refer to an ophthamologist

21. Delivery • Timing and mode of delivery individualised • Intrapartum insulin infusion with glucose monitoring • no contraindication for Breast feeding either with insulin or oral hypoglycemic agents

22. Pre-conception Counselling • Allows for optimisation of diabetic control prior to conception, and assessment of the presence of complications like hypertension, nephropathy, and retinopathy • Should counsel that good control and lower hba1c lower the risk of congenital abnormalities and improve outcome • If necessary, proliferative retinopathy may be treated with photocoagulation prior to conception • Contraindications to pregnancy only :ischemic heart dx, untreated proliferative retinopathy, severe renal impairment(creatinine>250 mmol/L)

23. Gestational diabetes Definition Carbohydate intolerance of variable severity first recognised during the present pregnancy. This includes women with preexisting but previously unrecognised diabetes

24. Pathophysiology • Significant hormonal changes affects carbohydrate metabolism during pregnancy . • This happens because of the increase of human placental lactogen HPL and cortisol, both of them are insulin antagonist. • These changes are most marked during the 3rd trimester . • To balance these changes maternal pancreas secretes increased amounts of insulin to maintain carbohydrate metabolism. • It affects 2-4% of pregnancies

25. Gestational diabetes No consensus for 4 decades!

26. Gestational diabetes • Should all pregnant women be screened or only those with risk factors? • Is it safe to screen all? • Which screening test and which diagnostic test are the most reliable? • Which cut-off values should we use? • What are the risk for mothers and babies and can treatment improve outcome? • What are the connection between gestational diabetes and type 2 DM? • Is it physiological or pathological ?

27. Gestational diabetes • Screening of diabetes in pregnancy 24-28 weeks • No single test proved to be perfect. • Urinary glucose is completely unreliable. • A full glucose tolerance test is would be ideal but is expensive and time consuming . • Random blood sugar of 5.8 mmol, has only 60% sensitivity . • Glucose challenge test GCT is using 50 gm glucose without fasting and measure the blood glucose after one hour and should not be greater than 7.8 mmol , the sensitivity is improved by 80%

28. Definition of diabetes . • WHO has defined diabetes as either fasting blood glucose of 7.8 mmol/l or more than 11mmol/l 1-2 hours following 75 grams of oral glucose load. • A good glycemic control during pregnancy or even before is needed because of the direct relationship between the blood glucose level and the fetal and maternal complications. • Any diabetic woman who plan to get pregnant should insure that their diabetes is optimally controlled to reduce the risk of obstetrical complications.

29. Gestational diabetes • Screening and diagnosis In general, risk factor includes: 1. age>25y 2. BMI > 25 3. previous GDM 4. Family hx of DM in 1st degree relative 5. previous macrosomic baby (>4 kg) 6. polyhydramnios 7. large for date baby in current pregnancy 8. previous unexplained stillbirth

30. Gestational diabetes Screening Fasting / random glucose/ glucose challenge test(50gm) Diagnosis Glucose tolerance test

31. Gestational diabetes

32. Gestational diabetes • Incidence 2-4% more common in Asian and Indian women In developed countries, increasing trend because of epidemic of obesity

33. Gestational diabetes Clinical significance of GDM • High incidence of macrosomia, and adverse pregnancy outcomes, • A significant proportion(30%) identified as GDM in fact have DM before pregnancy

34. Gestational diabetes • Women with glucose intolerance just above normal range are at low risk for pregnancy complications, those with more severe glucose intolerance approaching the criteria of diabetes are at risk of neonatal complications

35. Fetal complications • Macrosomia (>4 kg) risk is 16-29% as compared to 10% in control • Increase in caesarean delivery, intrumental deliveries ( forceps/vacuum), birth trauma, such as brachial plexus injuries , clavicular fractures • Increase in neonatal hypoglycemia (24% ), hyperbilirubinemia, hypocalcemia, polycythemia • Children are at risk of type 2 DM and obesity in life

36. Maternal complications • Increase risk of hypertensive disorders • Increase risk of caesarean and intrumental deliveries • Increased Risk (40-60%) of developing type 2 DM within10-15 yr.

37. Gestational diabetes • Management is similar as preexisting DM • Need for glucose monitoring • Start with Diet control • Commence insulin for poor control • Delivery plan should be individualised

38. Gestational diabetes • In view of risk of developing type 2 DM 30%, the woman should be screened annually for DM on yearly basis.

39. Diabetes and PregnancyConclusion • Preexisting DM in pregnancy • Good glucose control is important for decreasing morbidities • Insulin is still the gold standard of tx in pregnancy • Increasing evidence for clincial effectiveness for treatment with oral hypoglycemic agents

40. Diabetes and pregnancyconclusion (2) Gestational diabetes • no consensus • The morbidities increases as glucose level approaching the diagnosis as DM • Possible that treatment improves outcomes • Overlap with preexisting DM, esp type2 • Long term implication for health of the mother and baby

41. Thank You