Gestational diabetes

1. Gestational Diabetes (GDM)
Gill Spyer

2. Summary
• What is it?
• Who gets it
• How is it identified?
• What are the implications?
• What is the treatment
• Identifying other forms of diabetes presenting
in pregnancy

3. What is GDM?
“Gestational diabetes mellitus is defined as glucose
intolerance that first occurs or is first identified during
pregnancy.”
BUT …
What is a normal blood glucose
in pregnancy?

4. A: Patterns of glycemia in normal pregnancy (gestational week 33.8 ± 2.3) across 11 studies
published between 1975 and 2008.
Teri L. Hernandez et al. Dia Care 2011;34:1660-1668

5. Who is at risk?
• BMI above 30 kg/m2
• previous macrosomic baby weighing 4.5 kg or
above
• previous gestational diabetes
• family history of diabetes (first-degree relative
with diabetes)
• minority ethnic family origin with a high
prevalence of diabetes.
Offer women with any one of these risk factors
testing for gestational diabetes

6. What are the implications of raised bg
in pregnancy?
• Fetal outcomes
- LGA/macrosomic baby (>90th centile/ bwt>4Kg)
- Shoulder dystocia
- Hypoglycaemia
- Hyperbilirubinaemia
- Stillbirth/perinatal death
• Maternal outcomes
- Preeclampsia
- Preterm delivery
- Caesarian section
- Postnatal glucose intolerance/diabetes

7. Birth weight
Insulin mediated growth of
fetus
Pedersen 1977
Glucose sensing by fetal
pancreas
Insulin secretion by fetal
pancreas
Maternal Glucose

8. At what level of glycaemia does risk
increase?
• Difficult to define due to …
• Different methods of assessing eg 50g/100g
OGTT vs 75g OGTT
• Different thresholds and targets in pregnancy
eg ADA/WHO/NICE etc
• Lack of outcome data from big RCTs until
relatively recently.
• Likely no cut off but a continuum

9. • Aim to clarify the risks of adverse outcomes associated with various degrees of
maternal glucose intolerance less severe than that in overt diabetes mellitus.
• 25505 women 24-32 weeks gestation.
• 15 centers in 9 countries
• All underwent 75g OGTT. Blinded if fpg<5.8 and 2h bg<11.1
• Primary outcomes bwt above 90th centile, Caesarian section, fetal
hypoglycaemia, cord blood c-peptide level >90th centile
• Secondary outcomes delivery before 37 weeks, shoulder dystocia or birth
injury, need for neonatal care, hyperbilirubinaemia and preeclampsia
CONCLUSIONS
Strong, continuous associations of maternal blood glucose below those of
diabetes with increased birth weight and increased cord blood c-peptide levels

10. What level of glycaemia is associated
with risk?

11. Effect of treatment

12. ACHOIS Study
1000 women
Intervention
490
QDS BM testing
FPG 3.5-5.5
2h glucose<7.0
20% required insulin
Routine care
510
Unaware of diagnosis*
Standard care
3% required insulin
Women with at least 1 risk factor for GDM or positive 50g OGTT (1h
glucose >7.7) offered 75g OGTT at 24 to 34 weeks. Randomised if fpg<7.8
and 2h glucose 7.8 -11 mmol/l. Previous GDM excluded
*If indications arose suggestive of
diabetes further assessment for
GDM was permitted with
Treatment as appropriate

13. Primary endpoints

14. Secondary endpoints

15. Headlines
Treatment of GDM…
• reduced serious perinatal outcomes and
• Lowered fetal birthweight but
• Increased rate of IOL and earlier delivery but
did not increase Caesarian section rates
• Increased admission to NNU

16. Together HAPO and ACHOIS tell us that maternal
hyperglycaemia LESS severe than that used to define
diabetes is related to clinically important perinatal
Disorders. The effects can be reduced by treatment,
although a threshold for the need for treatment is not
established
Summary

17. What is the best treatment?
• Insulin is the “gold standard” and has been
shown to be both safe and benficial in
improving outcomes
• Only 2 other classes of drug have safety and
outcome data in pregnancy
- metformin
- sulphonylureas (glibenclamide)

18. Use of oral agents in GDM

19. MiG Study
751 women with
GDM
20-33 weeks
gestation
363 Metformin
titrated to max
2500mg
+/_ Insulin (46%)
378 Insulin

20. Results
• No increase in perinatal complications based
on a composite of neonatal hypoglycamia,
respiratory distress, need for phototherapy,
birth trauma, premature birth, 5 min apgar<7
• Higher frequency of preterm birth in
metformin group not associated with higher
rates of complications
• No difference in birthweight or LGA babies
• Women preferred treatment with metformin

21. Fig 1 Forest plots of birth weight in the meta-analyses comparing glibenclamide and
metformin with insulin or with each other in women with gestational diabetes.
Montserrat Balsells et al. BMJ 2015;350:bmj.h102
©2015 by British Medical Journal Publishing Group

22. Summary of results
• Glibenclamide is associated with higher birth weight
and greater neonatal hypoglycaemia than insulin.
Some studies report higher rates pre-eclampsia and
neonatal jaundice
• Metformin equivalent neonatal outcomes to insulin
but less maternal weight gain, better post prandial bg
and lower hypertension in pregnancy but earlier
delivery and greater treatment failure compared with
insulin
• Metformin lower birthweight and macrosomia, lower
maternal weight gain compared with glibenclamide
• Treatment failure 26.8 vs 23.5 (MF v Glibenclamide)

23. Current NICE targets for GDM
• Diagnose gestational diabetes on 75g OGTT if
a fasting plasma glucose level>5.5 mmol/litre or
a 2-hour plasma glucose level of 7.8 mmol/litre or above.
• Advise pregnant women with any form of diabetes to maintain their
capillary plasma glucose below the following target levels, if these are
achievable without causing problematic hypoglycaemia:
fasting: 5.3 mmol/litre
and
1 hour after meals: 7.8 mmol/litre or
2 hours after meals: 6.4 mmol/litre
• Offer advice about diet and exercise first
• Offer metformin if not achieving targets within 1 to 2 weeks
• Offer insulin instead of metformin if metformin is contraindicated or
unacceptable to the woman or offer addition of insulin to metformin if
blood glucose targets are not met.

24. • Offer immediate treatment with insulin, with or without
metformin to women with gestational diabetes who have a
fasting plasma glucose level of 7.0 mmol/litre or above at
diagnosis.
• Consider immediate treatment with insulin, with or without
metformin for women who have a fasting plasma glucose
level of between 6.0 and 6.9 mmol/litre if there are
complications such as macrosomia or hydramnios.
• Consider glibenclamide in women whose blood glucose
targets are not achieved with metformin but who decline
insulin therapy or who cannot tolerate metformin

25. Case report 1
• 34 yo slim women presents in second
pregnancy, commences prandial insulin at 22
weeks gestation.
• Previous GDM
• Fpg 4.9 Hba1c 49
• Mother and brother have T2 diabetes
DIAGNOSIS? HNF 1a

26. Case 2
• 18 yo female presented to GP 6 weeks pregnant
• No symptoms
• Routine bloods. Random BS 6.2 Hba1c 68
• BMI 29
• No family history of diabetes
DIAGNOSIS?
GAD antibodies>2000
IAA2 >526 (0-14.9U/ml)
Type 1 diabetes
• Started on basal bolus insulin

27. Case 3
• 33 yo recently relocated from Manchester
currently 15 weeks 4th pregnancy on basal
bolus insulin. BMI around 30
• Diagnosed with diabetes age 7
• GAD negative but ?previous admission with
DKA
• Adopted but in touch with mother (now
deceased, maternal aunt and cousin (no
known diabetes)

28. Case 3 cont…
• Knew of very strong FH on fathers side and
“many affected half siblings”.
• 4 children 11yo boy, 8 yo twins and 5 yo girl.
Tests BMs occasionally with own meter.
Reports 1 of twins cbs 7 - 8
GAD negative
Urinary cpeptide > 1.8
Genetic analysis: m3243 ???
• Maternal aunt and cousin tested for mutation and
diabetes both negative.

29. Case 4
• 27 yo slim presents at 28 weeks
• OGTT 6.2 & 7.4 @ 2h
• Previous LGA baby
• No Fhx
• Current scan fetal AC > 90th centile
• Bms in range 6 -11
DIAGNOSIS? GCK

30. Case 4 cont…
• What is the management?

31. Case 5
• 21yo slim
• Half brother has type 1 diabetes
• Measuring “large for dates”
• OGTT 6.7 & 14.4 @ 2h Hba1c 44
DIAGNOSIS? GAD 13.6 (0-11)
IAA2 637.1 (0-14.9)
ZnT8 939 (0-64.99)
TYPE1 diabetes
• Successful outcome on diet and metformin only.
Currently normal bm’s post partum

32. Identifying other forms of diabetes
presenting in pregnancy
• Family History ie affected 1st degree relative,
young age at diagnosis
• Hba1c ie diabetic range?
• OGTT pattern of bg ie flat as in GCK
• Post pregnancy glucose tolerance – increased
suspicion if diabetes doesn’t resolve

33. GDM summary
• Mild maternal glucose intolerance is associated
with adverse maternal and fetal outcomes.
• Risk increases incrementally with maternal bg at
0,1 and 2h after 75g OGTT. There is no “cut off”
level at which risk increases
• Treatment to lower bg reduces adverse perinatal
outcomes. Metformin and insulin equivalent but
higher risk of treatment failure with MF
• Glibenclamide reduces maternal bg and is well
tolerated but less effective than MF and insulin

34. Cont…
• GDM is a heterogenous group of conditions.
Be vigilant for other forms of diabetes that
present in pregnancy.

35. HAPO glucose categories
fbg 1 hour 2 hour
Cat 1 < 4.2 <5.9 < 5.1
Cat 2 4.2 – 4.4 5.9 – 7.3 5.1 - 6
Cat 3 4.5 – 4.7 7.4 -8.6 6.1 – 6.9
Cat 4 4.8 - 4.9 8.7 – 9.5 7 – 7.7
Cat 5 5 – 5.2 9.6 – 10.7 7.8 – 8.7
Cat 6 5.3 – 5.5 10.8 – 11.7 8.8 – 9.8
Cat 7 > 5.5 > 11.7 >9.9