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Diabetes in Pregnancy

Diabetes in Pregnancy. Ass. Pro. : S. Rouholamin. Objectives. Discuss Gestational Diabetes Mellitus (GDM) and Treatment Recognize common problems of GDM in Pregnancy Discuss long term followup of Gestational Diabetes Mellitus (GDM) Discuss needs of pre-existing diabetes in pregancy.

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Diabetes in Pregnancy

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  1. Diabetes in Pregnancy Ass. Pro. : S. Rouholamin

  2. Objectives • Discuss Gestational Diabetes Mellitus (GDM) and Treatment • Recognize common problems of GDM in Pregnancy • Discuss long term followup of Gestational Diabetes Mellitus (GDM) • Discuss needs of pre-existing diabetes in pregancy

  3. Gestational Diabetes Mellitus

  4. Gestational Diabetes • Reduced sensitivity to insulin in 2nd and 3rd trimesters • “Diabetogenic State” when insulin production doesn’t meet with increased insulin resistance Hod and Yogev Diabetes Care 30:S180-S187, 2007 Crowther, et al NEJM 352:2477–2486, 2005 Langer, et al Am J Obstet Gynecol 192:989–997, 2005

  5. Gestational Diabetes • Human placental lactogen, leptin, prolactin, and cortisol result in insulin resistance • Lack of diagnosis and treatment-increased risk of perinatal morbidities Hod and Yogev Diabetes Care 30:S180-S187, 2007 Crowther, et al NEJM 352:2477–2486, 2005 Langer, et al Am J Obstet Gynecol 192:989–997, 2005

  6. Gestational Diabetes Occurs in 2-9% of pregnancies ~135,000 cases in U.S. annually Management can include insulin (usually preferred, better efficacy) or sulfonylureas (in very select cases) Am J Obstet Gynecol 192:1768–1776, 2005 Diabetes Care 31(S1) 2008 Diabetes Care 25:1862-1868, 2002

  7. Gestational Diabetes and Type 2 Diabetes Risk • Gestational Diabetes should be considered a pre-diabetes condition • Women with gestational diabetes have a 7-fold future risk of type 2 diabetes vs.women with normoglycemic pregnancy Lancet, 2009, 373(9677): 1773-9

  8. Gestational Diabetes-Screening • Screen all very high risk and high risk • Very high risk: Previous GDM, strong FH, previous infant >9lbs • High risk: Those not in very high risk or low risk category

  9. Gestational Diabetes-Screening • Low Risk (all of following) • Age <25 years • Weight normal before pregnancy • Member of an ethnic group with a low prevalence of diabetes Diabetes Care 31(S1) 2008

  10. Gestational Diabetes-Screening • Low Risk (all of following)(cont’d) • No known diabetes in first-degree relatives • No history of abnormal glucose tolerance • No history of poor obstetrical outcome Diabetes Care 31(S1) 2008

  11. Gestational Diabetes Screening • 2 step approach oral glucose tolerance test (OGTT) • 1) 50gm 1 hour OGTT • 2) 100gm 2 hour OGTT

  12. Gestational Diabetes-Screening • GDM screening at 24–28 weeks: • Two-step approach: • 1) Initial screening: plasma or serum glucose 1 h after a 50-g oral glucose load • Glucose threshold • 140 mg/dl identifies 80% of GDM • 130 mg/dl identifies 90% of GDM Diabetes Care 31(S1) 2008

  13. Gestational Diabetes-Screening • GDM screening at 24–28 weeks: • Two-step approach (cont’d) • 2) 3 hour OGTT* (100g glucose load) Fasting: >95 mg/dl (5.3 mmol/l)1 h: >180 mg/dl (10.0 mmol/l)2 h: >155 mg/dl (8.6 mmol/l)3 h: >140 mg/dl (7.8 mmol/l) *2 of 4 Diabetes Care 31(S1) 2008

  14. Gestational Diabetes Management • Dietician • Diabetes Educator • Consider referral to Diabetologist or Endocrinologist • Moderate Physical Activity ~30 minutes daily when appropriate Summary and Recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus Diabetes Care 30:S251-S260, 2007

  15. Glucose Control in GDM • Preprandial: <95 mg/dl, and either: 1-h postmeal:<140 mg/dl or 2-h postmeal: <120 mg/dl andUrine ketones negative Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. The Organizing Committee. Diabetes Care 21(2):B161–B167, 1998

  16. Gestational Diabetes-Medications • Patients who do not meet metabolic goals within one week or show signs of excessive fetal growth • Insulin has been the usual first choice • Sulfonylureas (glyburide) may be used in select patients • Other diabetes medications not recommended in GDM Summary and Recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus Diabetes Care 30:S251-S260, 2007 Langer et al N Engl J Med 343:1134–1138, 2000

  17. Diabetes MedicationsInsulins-Safety • Aspart, Lispro, NPH, R, Lispro protamine all Category B and used in pregnancy • All other insulins Category C • Human Insulins-Least Immunogenic • Breastfeed-All insulins considered safe Data from Package Inserts

  18. Gestational Diabetes-Management • Fasting, pre-meal, 2-hour post-prandial blood glucose probably all important • Mean blood glucose >105-115, greater perinatal mortality • A1C in GDM probably not important Am J Obstet Gynecol 192:1768–1776, 2005 ADA Position Statement Pettit, et al Diabetes Care 3:458–464, 1980 Karlsson, Kjellmer Am J Obstet Gynecol 112:213–220, 1972 Langer, et al Am J Obstet Gynecol 159:1478–1483, 1988

  19. Insulin Dosing-GDM • Insulin dosing: • Can use usual weight based dosing (i.e., 0.5 u/kg) • Practical dosing can be to start 10 units NPH with evening meal • Most will titrate to BID, with eventual addition of Regular or Rapid Acting BID

  20. Alternate Insulin Dosing in GDM • Regular or rapid acting (lispro or aspart) with meals, NPH at bedtime • NPH + Regular or rapid acting in AM, regular or rapid acting at supper, NPH at bedtime • Titrate insulin based on SBGM values, tested fasting, pre-meal, 2 hour post-meal, bedtime, occasional 3 AM.

  21. GDM Complications Macrosomia Fractures Shoulder dystocia Nerve palsies (Erb’s C5-6) Neonatal hypoglycemia Pregnancy outcomes can be very poor with HTN/nephropathy Gabbe, Obstetrics: Normal and Problem Pregnancies 2002

  22. Gestational Diabetes: Post-natal • Fasting glucose rechecked 6-12 weeks following delivery • Every 6 months thereafter to be screened for type 2 diabetes • Higher risk of developing Type 2 Diabetes Kitzmiller, et al Diabetes Care 30:S225-S235, 2007

  23. Metabolic changes in pregnancy • Lipid metabolism: • Increased lipolysis (preferential use of fat for fuel, in order to preserve glucose and protein) • Glucose metabolism: • Decreased insulin sensitivity • Increased insulin resistance

  24. Metabolic changes in pregnancy • Increased insulin resistance • Due to hormones secreted by the placenta that are “diabetogenic”: • Growth hormone • Human placental lactogen • Progesterone • Corticotropin releasing hormone • Transient maternal hyperglycemia occurs after meals because of increased insulin resistance

  25. Diabetes in Pregnancy:Clinical implications Shoulder dystocia Fetal macrosomia

  26. Diabetes in Pregnancy: Clinical Implications • Obstetric complications (cont’d.): • Preterm delivery • Intrauterine fetal demise • Traumatic delivery (e.g., shoulder dystocia) • Operative vaginal delivery • vacuum-assisted • forceps-assisted

  27. Diabetes in Pregnancy: Clinical Implications • Fetal macrosomia • Disproportionate amount of adipose tissue concentrated around shoulders and chest • Respiratory distress syndrome • Neonatal metabolic abnormalities: • Hypoglycemia • Hyperbilirubinemia/jaundice • Organomegaly • Polycythemia • Perinatal mortality • Long term predisposition to childhood obesity and metabolic syndrome

  28. GDM: Risk factors • Maternal age >25 years • Body mass index >25 kg/m2 • Race/Ethnicity • Latina • Native American • South or East Asian, Pacific Island ancestry • Personal/Family history of DM • History of macrosomia

  29. GDM: Diagnosis • Fasting blood glucose >126mg/dL or random blood glucose >200mg/dL • 100 gm 3-hour glucose tolerance test (GTT) with 2 or more abnormal values

  30. Management:Glycemic control • Glycosylated Hemoglobin A1C (Hgb A1C) level should be less than or equal to 6% • Levels between 5 and 6% are associated with fetal malformation rates comparable to those observed in normal pregnancies (2-3%) • Goal of normal or near-normal glycosylated hemoglobin (Hgb A1C) level for at least 3 months prior to conception • Hgb A1C concentration near 10% is associated with fetal anomaly rate of 20-25%

  31. Management:Overview • Nutrition therapy • Home self glucose monitoring • Medical therapy if glycemic control not achieved with diet/exercise • Subcutaneous insulin • Oral hypoglycemic agents (Glyburide, Metformin) • Antenatal monitoring

  32. Management: Glycemic Control • Blood glucose goals during pregnancy • Fasting < 95mg/dL • 1-hr postprandial < 130-140mg/dL • 2-hr postprandial am < 120mg/dL • 2 am < 120mg/dL • Nocturnal glucose level should not go below 60 mg/dL • Abnormal postprandial glucose measurements are more predictive of adverse outcomes than preprandial measurements

  33. Management:Nutrition • Caloric requirements: • Normal body weight - 30-35 kcal/kg/day • Distributed 10-20% at breakfast, 20-30% at lunch, 30-40% at dinner, up to 30% for snacks (to avoid hypoglycemia) • Caloric composition: • 40-50% from complex, high-fiber carbohydrates • 20% from protein • 30-40% from primarily unsaturated fats

  34. Management:Subcutaneous Insulin Therapy • Insulin requirements increase rapidly, especially from 28 to 32 weeks of gestation • 1st trimester: 0.7-0.8 U/kg/d • 2nd trimester: 0.8-1 U/kg/d • 3rd trimester: 0.9-1.2 U/kg/d

  35. Management:Oral Hypoglycemic Agents • Glitazones (Avandia, Actos) • Sensitize muscle and fat cells to accept insulin more readily • Decrease insulin resistance • Sulfonylureas • Augment insulin release • 1st generation • Concentrated in the neonate  hypoglycemia • 2nd generation (Glyburide) • Low transplacental transfer • Biguanide (Metformin, aka Glucophage) • Increases insulin sensitivity • Crosses placenta

  36. Management Summary:Pregestational Diabetes • Referral to perinatologist and/or endocrinologist • Multidisciplinary approach • Regular visits with nutritionist • Hgb A1C every trimester • Fetal Echocardiogram • Level II ultrasound • Opthamologist • Baseline kidney and liver function tests

  37. Management Summary:Pregestational Diabetes • Optimize glycemic control – frequent insulin dose adjustments • Type 1: often have insulin pump • Type 2: subcutaneous insulin • Fetal monitoring starting at 28-32 weeks, depending on glycemic control • Ultrasound to assess growth at 36 weeks • Delivery at 38-39 weeks

  38. Management Summary:GDM • Begin with diet / walk after each meal • If borderline/mild elevations, consider metformin (start at 500 mg daily) • Counsel about increased PTD rates • Unlikely pre-existing DM • If elevations start out moderate to severe or metformin fails, proceed to subcutaneous insulin therapy • NPH (long acting) • Humalog/Novalog (short acting)

  39. Management Intrapartum • Attention to labor pattern, as cephalopelvic disproportion may indicate fetal macrosomia • Careful consideration before performing operative vaginal delivery • Hourly blood glucose monitoring during active labor, with insulin drip if necessary • Notify pediatrics if patient has poorly controlled blood sugars antepartum or intrapartum

  40. Management Postpartum • For patients with pregestational diabetes, halve dose of insulin and continue to check blood glucose in immediate postpartum period • For GDM patients who required insulin therapy (GDMA2), check fasting and postprandial blood sugars and treat with insulin as necessary • For GDM patients who were diet controlled (GDMA1), no further monitoring nor therapy is necessary immediately postpartum

  41. Management Postpartum • For all GDM patients, perform 75 gram 2-hour OGTT at 6 week postpartum visit to rule out pregestational diabetes • Most common recommendation is for primary care physician to repeat 2-hour OGTT every three years

  42. Case Study • 28 y/o caucasian female • 2nd pregnancy • 1st pregnancy at age 22, term male infant, 10 lbs 2oz, normal delivery • “Thinks had high blood sugar” • Very high risk (>9 lb infant, possible GDM)

  43. Case Study • No other significant medical history No tobacco • Physical Exam: VS normal 5’ 2” 210 lbs BMI 38.4 Remainder consistent with 12 weeks gestation

  44. Case Study • 26 weeks, no problems, maybe slightly large for dates • 12 lb weight gain • Went directly to 3 hour GTT (100g)

  45. Case Study • FBG: 94 ( > 95) • 1 hour: 192 (>180) • 2 hour: 160 (>155) • 3 hour: 149 (>140) • 3 of 4 values abnormal= GDM

  46. Case Study • Referred to Diabetes Educator and Dietician • SMBG: FBG, pre-meal, 2 hour post-prandial, HS, 3 am prn • Meal Plan • No contraindications to exercise, encouraged to walk 15 min/daily

  47. Glucose Control in GDM • Preprandial: <95 mg/dl, and either: 1-h postmeal:<140 mg/dl or 2-h postmeal: <120 mg/dl andUrine ketones negative Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. The Organizing Committee. Diabetes Care 21(2):B161–B167, 1998

  48. Case Study • Returns one week later • Has been following meal plan “90% of time” • Has walked 15 minutes 2 times • Has 4 FBG > 100 • 6 other values above target

  49. Case Study • Referred to Diabetes Educator for insulin start • NPH 10 units, 3 units Insulin aspart BID • Phone followup q 3 days • Continues appropriate clinic appointments

  50. Case Study • 1-2 SMBG values out of target 1st week • 3 weeks later, FBG, 2 hour post lunch and 2 hour post supper elevated about ~50% of time • NPH increased in PM (or could move to HS), insulin aspart added at lunch (2 or 3 units) and increased at supper

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