PDA ECHO: INSULIN THERAPY IN PREGNANT WOMENCynthia Halili-Manabat, M.D., PhD Internal Medicine October 2010
abstract goal in pregnancy complicated by diabetes is to maintain maternal glucose levels as near normal as possible throughout the pregnancy because near normal glycemia has been shown to decrease the prevalence of neonatal hypoglycaemia, macrosomia, intra-uterine death and caesarean delivery steps to achieve normal glucose during pregnancy include medical nutrition therapy and the additional of insulin, if goals are not met
abstract only human NPH insulin, regular human insulin and the rapid acting insulin analogs, lispro and aspart, are approved for use during pregnancy Lispro or Aspart is preferable to regular human insulin fifty percent of the insulin is given as a basal dose using NPH insulin and the other 50% as boluses before meals with lispro or aspart.
abstract the total daily insulin dose may be computed based on the current weight of the patient and stage of pregnancy as follows: prepregnancy, 0.6 U/kg/d first trimester (wk 1-12), 0.7 U/kg/d second trimester (wk 13-28), 0.8 U/kg/d third trimester (wk 29-34), 0.9 U/kg/d term (wk 35-39), 1.0 U/kg/d these doses are only starting doses and need to be adjusted based on results of home glucose monitoring
Fetal Hyperinsulinemia LGA or macrosomia are associated with birth trauma (shoulder dystocia) 0.6-1.4% in fetuses weighing 2500-4000g 5-9% in fetuses weighing >4000g Associated with neonatal hypoglycemia after infant is delivered and no longer exposed to maternal hyperglycemia
Management of Hyperglycemia in Pregnancy CGMS mean fasting glucose 75mg/dL peak post-prandial glucose 110mg/dL Medical Nutrition Therapy Weight control Carbohydrate restriction Frequent self-monitoring of blood glucose Insulin
When to Start Insulin When MNT fails Glycemic goals: Premeals 60-90mg/dL 1-hour postprandial <140mg/dL 2-hour postprandial <120-130mg/dL
Problem with Regular Insulin Slow onset of activity Inconvenient for patient (administered 30-60minutes prior to meal) Long duration of activity Potential for late postprandial (4-6hours) hypoglycemia Lasts up to 12hours
Insulin Lispro in Pregnancy More efficacious than human regular insulin to normalize blood glucose levels in gestational and pre-gestational diabetic women Rapidly lowered postprandial glucose levels, thereby decreasing A1c levels, with fewer hypoglycemic episodes, and without increasing anti-insulin antibody levels Similar neonatal outcomes versus regular insulin Improved patient satisfaction Especially helpful in women with hyperemesis or gastroparesis because they can be dosed after meals
Insulin Aspart in Pregnancy The overall safety and effectiveness of insulin aspart is comparable to regular human insulin in pregnant women with GDM/pregestational DM. Insulin aspart was more effective than regular insulin in providing postprandial glycemic control. Patients showed greater treatment satisfaction with Aspart.
Insulin Glulisine in Pregnancy There is inadequate data on glulisine use in pregnancy.
Insulin Glargine in Pregnancy Glycemic control, birthweight, and prevalence of macrosomia and neonatal morbidity were similar to human insulin Rate of congenital malformations comparable to NPH insulin Glargine is not approved for use in pregnancy
NN304-1687: Insulin Detemir in Pregnancy Study Randomised, parallel-group, open-labelled, multinational trial comparing the efficacy and safety of insulin detemir versus NPH insulin, used in combination with aspart as bolus insulin, in the treatment of pregnant women with type 1 diabetes Expected number of 240 completed pregnancies with 120 subjects in each arm To be completed 2010
How to Give Insulin 50% of total daily insulin as basal insulin using NPH, 50% as boluses before meals with rapid analog Predicted total daily insulin requirement Prepregnancy 0.6u/kg/d First trimester 0.7u/kg/d Second trimester 0.8u/kg/d Third trimester 0.9u/kg/d Term (wk 35-39) 1.0u/kg/d Rapidly adjust dose based on SMBG
How to Give Insulin NPH: 1/6 of total daily insulin dose administered every 8hours Lispro or Aspart: 1/6 of total daily insulin dose given before meals Monitor BGs before and 1hour after meals Goals: 65-90 mg/dL before meals <120 mg/dL after meals
Continuous Subcutaneous Insulin Infusion Pump CSII versus MDI in pregnancy RCTs show equivalent glycemic control and maternal and perinatal outcomes CSII- multiple adjustable basal rates can be especially useful for patients with daytime or nocturnal hypoglycemia or a prominent dawn phenomenon Disadvantages of CSII: cost, potential for marked hyperglycemia and risk of DKA as a consequence of insulin delivery failure
Glycemic Control and Insulin Treatment during Delivery Goal: maintain normoglycemia in order to prevent neonatal hypoglycemia Target CGBs 80-110 mg/dL during labor CBG every hour during labor, or every 2-4 hours if stable CBG >100mg/dL: NS or LR at 100cc/hr CBG <100mg/dL: supplemental 5% dextrose infusion at 100cc/hr
Glycemic Control and Insulin Treatment during Delivery CBG >120mg/dL: 2-4 units regular insulin IV every hour that CBG >120mg/dL (or RI incorporated into IV) After expulsion of placenta, requirement of insulin will fall precipitously Postpartum requirements drop to 1/3 to ½ of their previous insulin dosages; no insulin in first 24-48hours
Postpartum During lactation: postprandial glucose goals <150mg/dL to minimize high glucose levels in breast milk Stimulate hyperinsulinemia and accelerate hunger in the infant Contribute to excessive weight gain, obesity, and metabolic syndrome later in life Human insulin and insulin analogs appear in breastmilk directly proportional to serum levels in maternal blood, but they are not absorbed in the gut
Summary Rapid achievement of normoglycemia with limited weight gain is critical to optimize maternal and fetal outcomes in all women with diabetes during pregnancy. Lispro and Aspart have been tested and found to be safe and effective during pregnancy. Their use over regular insulin has been shown to result in improved glycemic control, fewer hypoglycemic episodes, and improved patient satisfaction. 2 to 3 doses of NPH insulin may be used to provide basal insulin needs. Neither glargine nor detemir is approved for use in pregnancy.