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Diabetes & Pregnancy

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A review of evidence based practice

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Diabetes & Pregnancy

  1. 1. Dhammike Silva
  2. 2.  Introduction
  3. 3.   A metabolic condition characterized by chronic hyperglycaemia as a result of defective insulin secretion, insulin action or both What is DM?
  4. 4.   Type 1(IDDM)  Type 2(NIDDM)  Gestational diabetes  Others  Genetic defects in insulin processing or action  Endocrinopathies  Drugs  Exocrine pancreatic defects  Genetic syndromes associated with DM Types
  5. 5.   Placental Diabetogenic hormones  Increased Plasma Cortisol levels  State of insulin resistance  Increased body weight and caloric intake  Pregestational diabetes becomes worse during Pregnancy & GDM develops when the pancreas cannot overcome the effect of these hormones Is Pregnancy Diabetogenic ?
  6. 6.  Diabetes & Pregnancy Diabetes in Pregnancy GDM 90% Chronic DM 10% Incidence rising
  7. 7.   Maternal Fetal Miscarriages FGR Preeclampsia Preterm labour Birth trauma IUD / Still births IOL Macrosomia Increased maternal morbidity Congenital malformations Future risk for Type 2 DM Postnatal hypoglycemia Worsening of Retinopathy / Shoulder dystocia Nephropathy RDS LSCS / Operative vaginal delivery Polycythemia & Jaundice Sepsis Complications
  8. 8.   Obesity  Diabetes mellitus  Reproductive problems  Metabolic syndrome The child - later on….
  9. 9.  History
  10. 10.   Greek physician in 80 to 138 C.E.  Described diabetes mellitus “melting of flesh and limbs into urine” “ One cannot stop them from making or drinking water” Aretaeus of Cappadocia
  11. 11.   Started the first Diabetic pregnancy Clinic in 1924  Achieved from 50% to 90% survival rate among babies born Her studies showed about strict diet control and early delivery improved outcome Priscilla White, MD
  12. 12.  Screening
  13. 13.  Screening
  14. 14.   Importance 1. Intervention in pregnancy will improve out come 2. Greater risk in developing Type 2 DM in later life Diabetes in pregnancy , NICE guideline 3, 2015 ACHOIS – Australian Carbohydrate intolerance study in preg women 2005 Screening
  15. 15.  Screening Screening 1st Trimester 2nd Trimester
  16. 16.   On selected population with 75 g 2 hour OGTT  Fasting Plasma Glucose can be used as a screening test in high risk population  50 g GCT has inconclusive data to support as a screening test  Evidence does not support HbA1c as a screening test Diabetes in pregnancy , NICE guideline 3, , 2015 Screening
  17. 17.   Gold standard to diagnose GDM is 75 g 2 Hour OGTT  Between 24 to 28 weeks  Can be performed or repeated up to 32 weeks Diagnosis
  18. 18.   Previous pregnancy - GDM  Early self monitoring of blood glucose  75 g OGTT at booking visit  Repeat OGTT between 24 to 28 weeks if booking OGTT normal  OGTT at 24 / 52 for other risk factors for GDM Diabetes in pregnancy , NICE guideline 3,, 2015 Diagnosis of GDM
  19. 19.   Obesity ( BMI > 30 Kg / m2 )  Ethnicity ( South Asians, Chinese )  Previous GDM  Family History of DM  Previous Macrosomia ( > 4.5 kg )  PCOS  Advanced maternal age  Previous unexplained perinatal death  Polyhydramnios  Smoking Diabetes in pregnancy , NICE guideline 3, Wednesday February 25th, 2015 Risk Factors for GDM
  20. 20.   Developed prior to HAPO  75 g 2 hour OGTT FPG 126 mg / dL 2nd Hour Plasma Glucose 140 mg / dL  Limitation HAPO detect more Macrosomic babies than from WHO criteria HAPO study. NEJM 2008 WHO Criteria
  21. 21.  Overt Diabetes
  22. 22.   Strong Continuous associations between glycaemic levels below those diagnostic of diabetes and adverse pregnancy outcome ( increase in birthweight and increased cord blood C- Peptide levels ) Hyperglycaemia α Adverse Pregnancy Outcomes HAPO study. NEJM 2008 HAPO
  23. 23.   25,505 pregnant women, 15 centres, 9 countries  Primary Outcomes BW > 90th % Cord blood serum C-peptide >90 % Primary CS Neonatal hypoglycaemia  Secondary Outcomes Premature delivery Shoulder Dytocia Intensive neonatal care Hyperbilirubinaemia Pre eclampsia HAPO NEJM 2008; 358:1991-2002 HAPO
  24. 24.  HAPO  Need to reconsider current diagnostic criteria ……
  25. 25.   Adopted from HAPO and other studies  From 24 to 28 weeks  FBS 92 mg/dL  1h 180 mg/dL  2h 153 mg/dL  Diagnosis requires only one threshold value exceeded International Ass of Diabetes and Pregnancy Study Groups . Diabetes Care 2010 IADPSG Criteria – 2008
  26. 26.  Diagnosis of GDM
  27. 27.  Preconception
  28. 28.   Diabetes carries increased risk for NTD  High dose Folic acid ( 5 mg / day ) From pre-conception to 12 / 52 of gestation significantly reduces the incidence of NTD Diabetes in pregnancy , NICE guideline 3, 2015 Folic Acid
  29. 29.   Pregestational DM associated with Adverse Pregnancy Outcomes ( APO )  Presence of complications of DM increase risk for APO  Sub optimal glycaemic control is associated with APO Diabetes in pregnancy , NICE guideline 3, 2015 Glycaemic Control
  30. 30.   BMI > 30 Kg / m2 associated with Increased incidence for IGT, HT, PPH, Caesarean sections, Macrosomia, Congenital malformations, Preterm births, Perinatal morbidity & mortality Diabetes in pregnancy , NICE guideline 3,, 2015 Obesity
  31. 31.   ACE Inhibitors / Angiotensin 2 Receptor Antagonist Associated APO Pre term births FGR Major Congenital malformations  Statins Associated APO Major Congenital malformations Thus all the drugs should be discontinued prior to conception or as soon as pregnancy is confirmed Diabetes in pregnancy , NICE guideline 3,, 2015 Drugs
  32. 32.   Degree of glycaemic control at conception is associated with congenital malformations and miscarriages  Good pregnancy out come is associated with HbA1c < 6.5 %  Advise against pregnancy if HbA1c > 10 % Diabetes in pregnancy , NICE guideline 3, Wednesday February 25th, 2015 HbA1c
  33. 33.   Measure in all pregestational DM at booking visit  Measure in T2 / T3 to asses level of risk in pre gestational diabetes  No use as a indicator for blood sugar control in T2 /T3 Diabetes in pregnancy , NICE guideline 3,, 2015 HbA1c
  34. 34.  Diabetes in Pregnancy
  35. 35.   GDM DM + Pregnancy Early pregnancy BS normal Elevated BS since before Usually no effect on organogenesis pregnancy Less likely to have congenital defects Effect during Diabetes disappears after delivery organogenesis More macrosomia More congenital fetal defects X 8 FGR common Difference between GDM & DM
  36. 36.  Gestational Diabetes
  37. 37.  Gestational Diabetes
  38. 38.  Pregestational Diabetes
  39. 39.  Pregestational Diabetes
  40. 40.  Antenatal Period
  41. 41.   Normalisation of blood glucose  Limited weight gain  Monitoring for anomalies and complications  Avoiding macrosomia  Planned delivery Strategy
  42. 42.   Significant improvement of major APO Macrosomia Shoulder Dystocia Primary Caesarean sections Still birth Diabetes in pregnancy , NICE guideline 3,, 2015 Medical Nutritional Therapy
  43. 43.   Some evidence on Post Prandial Exercise to improve Post Prandial Blood Glucose Diabetes in pregnancy , NICE guideline 3, Wednesday February 25th, 2015 Exercise
  44. 44.   OHG Offer if blood sugar targets not met with MNT & Exercise within 1 to 2 weeks  No significant difference in rates of major malformations between OHG group with non OHG group 10 RCT , OR 1.06, 95% CI 0.65 – 1.7 Diabetes in pregnancy , NICE guideline 3,, 2015 Pharmacology
  45. 45.   Safe in pregnancy  Offer if blood sugar targets not met with MNT & Exercise within 1 to 2 weeks Metformin
  46. 46.   In GDM, Metformin (alone or with supplemental insulin) is not associated with increased perinatal complications as compared with insulin. The women preferred metformin to insulin treatment.  Is a reasonable therapeutic option to Insulin* Australian New Zealand Clinical Trials Registry number, 12605000311651 *Diabetes in pregnancy , NICE guideline 3, Wednesday February 25th, 2015 MiG Trial
  47. 47.   Metformin in Gestational Diabetes: The Offspring Follow-Up (MiG TOFU)  2 year follow up of MiG Trial  Children exposed to metformin had larger measures of subcutaneous fat, but overall body fat was the same as in children whose mothers were treated with insulin alone. Diabetes Care 34:2279–2284, 2011 MiG TOFU
  48. 48.   The first OHG agent to have proven efficacy and safety in pregnancy  Minimal placental transfer  No significant difference in major adverse out comes when compared with Insulin But High treatment failure and Maternal hypoglycaemia Diabetes in pregnancy , NICE guideline 3, Wednesday February 25th, 2015 Langer et al. N Eng J Med 2000 Glibenclamide
  49. 49.   Can offer Glibenclamide to  Those on Metformin but refuses Insulin  Those not tolerating Metformin  Start at 2.5mg/day up to 20 mg /day Diabetes in pregnancy , NICE guideline 3, 2015 Glibenclamide
  50. 50.   No significant difference in major out come But Metformin is better tolerated Diabetes in pregnancy , NICE guideline 3, 2015 Glibenclamide Vs. Metformin
  51. 51.   Is the drug of choice  Offer Insulin if blood sugar targets not met with MNT, Exercise, Metformin  Offer Insulin +/- Metformin if FPG > 7.0 mmol /l at diagnosis ( 126 mg/dl )  Offer Insulin +/- Metformin if FPG > 6.0 to 6.9 mmol /l (108 mg/dl to 124 mg/dl if there are complications ( Macrosomia, Polyhydramnios ) Diabetes in pregnancy , NICE guideline 3, 2015 Insulin
  52. 52.   Rapid acting ( Lispro, Aspart, Glulisine )  No difference in HbA1c reduction  More hypoglycaemia  No difference in APO  Long acting ( Ditemir, Glargine )  Some evidence on HbA1c reduction  No difference in APO Diabetes in pregnancy , NICE guideline 3, Wednesday February 25th, 2015 Insulin
  53. 53.   Isophane Insulin ( Crystalline Zinc insulin with Protamine )  Good baseline control  1st line choice as the long acting Insulin Diabetes in pregnancy , NICE guideline 3, Wednesday February 25th, 2015 Neutral Protamine Hagedorn
  54. 54.   Type 1 DM FBS, Pre meal, 1 hour post meal & bed time glucose daily throughout pregnancy Type 2 DM / GDM on Insulin FBS, Pre meal, 1 hour post meal & bed time glucose daily through out pregnancy Diabetes in pregnancy , NICE guideline 3, Wednesday February 25th, 2015 Antenatal Blood Sugar Monitoring
  55. 55.   Maintain FBS 95 mg / dL 1 hr PPBS 140 mg / dL 2 hr PPBS 115 mg / dL  Maintain CBS > 4 mmol / L on Insulin or Glibenclamide Diabetes in pregnancy , NICE guideline 3, 2015 Antenatal Blood Sugar Monitoring
  56. 56.   Daily monitoring Vs. Weekly monitoring Daily monitoring is not cost effective & practical  Pre prandial Vs. Post prandial Post prandial group received more Insulin & had smaller babies Diabetes in pregnancy , NICE guideline 3,, 2015 Antenatal Blood Sugar Monitoring
  57. 57.   One hour PPBS Vs. Two hour PPBS  Peak blood sugar levels at 60 to 90 minutes  More acceptable & tolerable One hour PPBS preferable but no Significant difference in out come Diabetes in pregnancy , NICE guideline 3, Wednesday February 25th, 2015 Antenatal Blood Sugar Monitoring
  58. 58.   Ketone Bodies Test In Type 1 DM if unwell or in hyperglycaemia In Type 2 DM in hyperglycaemia Diabetes in pregnancy , NICE guideline 3, Wednesday February 25th, 2015 Antenatal Monitoring
  59. 59.  Delivery
  60. 60.   Type 1 or type 2 diabetes with no other complications to have an elective birth between 37+0 / 52 and 38+6 / 52 of pregnancy  Consider elective birth before 37+0 / 52 for type 1 or type 2 diabetes if there are metabolic or any other maternal or fetal complications  Advise women with gestational diabetes to give birth no later than 40+6 / 52  Consider elective birth before 40+6 / 52 for women with gestational diabetes if there are maternal or fetal complications Diabetes in pregnancy , NICE guideline 3, Wednesday February 25th, 2015 Delivery
  61. 61.  Post Partum Care
  62. 62.   Insulin-treated pre-existing diabetes should reduce their insulin immediately after birth and monitor their blood glucose levels  GDM should discontinue blood glucose-lowering therapy immediately after birth  In GDM Offer a FBS 6–13 weeks after the birth If a FBS not done by 13 weeks, offer FBS or HbA1c  Do not routinely offer a 75 g 2-hour OGTT  Offer an annual HbA1c for GDM who have a negative postnatal test for diabetes Diabetes in pregnancy , NICE guideline 3, Wednesday February 25th, 2015 Post Partum Care
  63. 63.   Continuous glucose monitoring (CGM)  Continuous subcutaneous insulin infusion (CSII) CGM carried in conjunction with CSII Have good Glycaemic control & minimal complications Diabetes in pregnancy , NICE guideline 3, Wednesday February 25th, 2015 Future
  64. 64.  References  Diabetes in pregnancy , NICE guideline 3, Wednesday February 25th, 2015  HAPO study. NEJM 2008  IADPSG. Diabetes Care 2010  Dewhurst's Text book of Obstetrics and Gynecology, 7th Edition  WHO, Diabetes in pregnancy, 2013
  65. 65.  Questions ?
  66. 66.  Thank You ! Thank You !!

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