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?
- 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
- 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