1. Diabetes and Pregnancy
Dr Wong Pui Yee, Bonnie
MBChB, MRCOG
FHKAM(OG), FHKCOG
Subspecialist in Fetal Maternal Medicine

2. 2 parts:
Preexisting DM and pregnancy
Gestational diabetes

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 level Risk
normal not increased
<8% %
>10% %

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
Polyhydramnio
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 drug is 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 with h’stix
Insulin may be need to be adjusted as gestation advances
Hba1c monitoring
Fetal monitoring with USG
Refer 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. No consensus for 4 decades!
Gestational diabetes
No consensus for 4 decades!

25. 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 ?

26. Gestational diabetes Screening and diagnosis
In general, the test is performed btn wk because at this point in gestation the diabetogenic effect of pregnancy is manifest and there is sufficient time remaining in pregnancy for therapy to exert its effect

27. 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. polyhydramnio
7. large for date baby in current pregnancy
8. previous unexplained stillbirth

28. Gestational diabetes Screening
Fasting / random glucose/ glucose challenge test(50gm)
Diagnosis
Glucose challenge test
(75gm/100gm ?)

29. Gestational diabetes Diagnosis WHO criteria 1998, 75 gm glucose
fasting hr (mmol/L)
Impaired fasting glucose
IGT <or = and
DM >or = or > or=11.1

30. Gestational diabetes Incidence 2-9%
more common in Asian and Indian women
In developed countries, increasing trend because of epidemic of obesity

31. 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

32. 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

33. 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

34. 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.

35. Gestational diabetes Does treatment improves outcomes?
Conflicting results
1. Cochrane datebase systemic review 2005 (3 studies only)
no difference in outcomes except neonatal hypoglycemia
2. Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS study) 2005 ( 490/510 subjects)
treatment of diabetes reduces serious perinatal morbility and may
improve the woman’s health-related quality of life

36. Gestational diabetes Large randomized study on going HAPO trial in USA
(Hyperglycemia and Adverse Pregnancy Outcome study)

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

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

39. Diabetes and Pregnancy Conclusion
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 pregnancy conclusion
(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 very much!