Diabetes in Pregnancy

1. Diabetes in Pregnancy Max Brinsmead PhD FRANZCOG February 2013

2. Types and Incidence • KNOWN DIABETIC (Before pregnancy) • Insulin dependent – Type 1 or Juvenile Onset Diabetes • NIDM – Type 2 or Maturity Onset Diabetic • Together account for <1% of pregnancies • GESTATIONAL DIABETES • Diagnosed during a pregnancy • May or may not resolve after pregnancy • Comprise 2 – 9% of pregnancies depending on the population

3. Glucose Metabolism in Pregnancy • Pregnancy is a diabetogenic stress • Results from antagonism of insulin by placental hormones • HPL, Sex steroids and corticosteroids • The diabetogenic stress increases as pregnancy advances • But reverses quickly after placenta delivers • BUT… • Facilitated transfer of glucose to the parasitic fetus  fasting hypoglycaemia

4. The Effect of Diabetes on Pregnancy •  Maternal blood sugar will •  Fetal blood sugar and… •  Fetal insulin • This causes… •  Fetal growth which  • Dystocia  Caesarean or shoulder difficulties  • Brachial plexus palsy • BUT • Fetal brain growth is reduced • Lung maturation is delayed • And the neonate is at risk of hypoglycaemia & hypocalcaemia

5. Effect of Diabetes on Pregnancy (2) •  Fetal blood sugar will cause •  Fetal glycosuria • Polyhydramnios • There is risk of intrauterine death • ?due to hypoxia • ?due to ketoacidosis • There is Rate of maternal Pre eclampsia • ?due to placental bed vasculopathy • There are Risks of Prematurity • Some of which is due to intervention on behalf of the mother

6. Extra Risks for Type 1 Diabetics • First trimester hyperglycaemia causes… • Rates of congenital malformation (CNS & Heart) • If there is diabetic vasculopathy then the inevitable kidney damages causes… • Rates of pre eclampsia • Risk of fetal growth retardation

7. The Effect of Pregnancy on Diabetes • Insulin antagonism  Insulin requirements • Pregnancy is a state of lipidolysis so IDDM patients are at risk of ketoacidosis • Especially during labour • Will be complicated by nausea, vomiting & slow gastric emptying • And altering energy expenditure • A desire for tight glucose control and a parasitic fetus puts the mother at risk of serious hypoglycaemia • Retinopathy and nephropathy may deteriorate rapidly • Insulin requirements change rapidly after delivery

8. Principles of Management • Family Planning • Preconception care • Stringent blood glucose control before pregnancy • Monitor HBA1c • Meticulous blood glucose control throughout pregnancy • Multidisciplinary care from Physician, Dietition, Nurse Educator and Obstetrician • Watch for known complications • Timely delivery • Appropriate mode of delivery • Family Planning

9. Controversies in Gestational Diabetes • Selective or universal testing • At least 50% missed unless all screened • Can obstetric outcomes be changed? • These questions answered by the 2005 ACHOIS study • Glucose challenge or GTT • 75G one hour test is best for screening • IADPSP recommends universal 1-step testing with 75g 2 hr test • Criteria for diagnosis • Criteria for the use of insulin • Role of oral hypoglycaemic drugs

10. The Effect of Treatment of Gestational Diabetes on Pregnancy OutcomesCrowther et al NEJM June 2005 • The ACHOIS study • RCT of approx. 1,000 pregnant women with gestational diabetes; standard care vs blood glucose control by diet +/- insulin • Risk of Perinatal Risk (i.e. death, shoulder dystocia, fracture and N palsy) reduced from 4% to 1%; RR=0.33 (CI 0.14 – 0.75) • Rate of Induction Labour; RR1.36 (CI 1.15 – 1.62) • Rate of NICU admissions; RR 1.13 (CI 1.03 – 1.23) • No difference in rate of Caesareans • Rates of depression and stress in mothers in the puerperium

11. Cost Effectiveness of Treatment for Gestational Diabetes Moss et al BMC Preg & Childbirth Oct 2007 • From the ACHOIS study • For every 100 women with abnormal GTT in pregnancy (mild gestational diabetes) offered treatment there was $60,000 additional costs • From pregnancy multidisciplinary care • Induction of labour (10 additional women) • Neonatal care admission (9 additional babies) • However saved 1 baby from perinatal death and 2 from neonatal complications • Estimated saving $80,000

12. Hyperglycaemia and Adverse Pregnancy Outcome Study Metzger et al NEJM May 2008 • The HAPO study • A prospective study of 25,505 women in 19 centres • All had a 2-hour 75-g GTT at 24 – 34 weeks • Those with Fasting GLUC > 5.7 or 2 hr >11.0 were identified and removed • Remainder followed without knowledge of the GTT result (a blinded prospective study) • Found significant positive associations between fasting, 1-HR and 2-HR GLUC and • LGA babies • Primary CS rates • Risk of neonatal hypoglycaemia

13. An RCT of Treatment for Mild Gestational Diabetes Landon et al NEJM October 2009 • The MFMU trial • 958 women in a number of US centres • All had an abnormal 3 Hr GTT but the fasting GLUC was <5.3 • Randomly assigned to treatment or observation • Treatment • Reduced mean fetal birthweight by 106g • Fewer babies <4 Kg (7.1% vs 14.5% • Less shoulder dystocia (1.5% vs 4.0%) • Fewer Cesareans (26.9% vs 33.8%) • Reduced risk of preeclampsia and gestational hypertension (8.6% vs 13.6%) • All these were significant differences

14. Criteria for Selective Testing • First degree affected relative • Age >35 years • Ethnic origin • Obesity BMI >30 • Poor obstetric history esp. “unexplained stillbirth” • Previous fetal macrosomia (>4.5Kg) • Clinical suspicion • Polyhydramnios • Macrosomia • Previous Gestational Diabetes

15. Criteria for the Diagnosis • May begin with Fasting and 2 hr Postprandial GLUC • If Fasting >7.8 or • 2 hr PP >11.0 then… • This patient requires insulin ASAP • Best test is the WHO 75G GTT • Diabetes is Fasting GLUC >5.4 or… • 2 hr PP >7.8 • IADPSP criteria • Fasting ≥ 5.1 • 1 hr ≥ 10.0 • 2 hr ≥ 8.5

16. Management of Gestational Diabetes • Diet • Abstinence from all simple sugars • Reduce fats and oils • Regular meals with complex CHO (low glycaemic index) • Exercise • Self-tested blood glucose 4x  once daily • Aim for Fasting GLUC <5.0 • And 2 hr PP 5.9 – 6.4 • Metformin or Insulin if targets not met • Cease any insulin at delivery • Repeat 75g GTT after 8 – 12 weeks

17. Role for Oral Hypoglycaemics • Use Metformin or Glibenclamide • Achieves the same outcomes as insulin if target GLUC are met • Better than insulin at controlling maternal weight • 7 – 46% will go on to require insulin

18. Management of Insulin Dependent Diabetes • Before Pregnancy • Normalise HBa1c • Folic acid 5 mg daily • Check kidney and retina • Multidisciplinay care • Self-tested blood glucose 4x daily • Aim for Fasting GLUC <5.0 • And 2 hr PP 5.9 – 6.4 • Prenatal diagnosis • 1st trimester screening by serum biochemistry + ultrasound • Routine morphology at 18w • Cardiac ultrasound at 22w • Scan for growth and umbilical Dopplers • 28 & 36w

19. An RCT of Metformin vs Insulin for Gestational Diabetes Rowan et al NEJM May 2008 • Neonatal hypoglycaemiaFrom Auckland New Zealand • 751 women randomised to Metformin or Insulin • 46% of those assigned to Metformin required supplemental insulin • Outcomes the same (Composite RR 0.99 CI 0.80-1.23) but women preferred Metformin • Respiratory distress • Prematurity • Jaundice • Birth Trauma • Low Apgar • Birthweight • Maternal outcomes

20. Delivery of the Pregnant Diabetic • Timing for Type 1 diabetics is often a juggle between difficult sugar control and fetal maturity • ?role for Betamethasone for the fetal lungs • Low threshold for Caesarean especially if fetal macrosomia is suspect • Most gestational diabetics induced at term i.e. >37 completed weeks • but wait for spontaneous or induced Cx ripening • Monitor GLUC in labour • May require dextrose and insulin by infusion for those who are insulin-dependant • Monitor the fetus in labour