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SH.ARBABI, M.D Endocrinology Center 18-OCT-2007

 Approximately 15 percent of women with GDM are placed on insulin therapy  With diet, percent of women with GDM will achieve normoglycemia  main purpose of drug intervention at these levels is to minimize the incidence of macrosomia 3

 Goals of medical nutritional therapy :  Achieve normoglycemia  Prevent ketosis  Provide adequate weight gain contribute to fetal well-being 4

 BMI < KCAL/Kg  BMI(22-27) 3O “  BMI(27-29) 24 “  BMI > 30 (12-15) “ 5

 Carbohydrate 40%  Protein 20%  Fat 40%  75-80% will achieve normoglycemia 6

 Tissue sensitivity to insulin  both fasting and postprandial  BG  Three times a week (20-30) minutes per session 7

 FBS >95mg/dL  1hpp>130 to 140 mg/dL  2hpp>120 mg/dL 8

 FBS >1O5mg/dl  1hpp>155 mg/dl  2hpp>130 mg/dl 9

 Varies in different populations (obesity, ethnic, demographic criteria)  but the majority of studies have reported a total insulin dose ranging from 50 to 90 units to achieve glucose control 10

 If insulin is required because the FBS is high, an intermediate- acting insulin, such as NPH insulin, is given bedtime  initial dose : 0.2 U/kg 11

 If postprandial BS are high: regular insulin or insulin lispro before meals  1.5 U per 10 gr CHO in the breakfast meal  1 U per 10 gr CHO in the lunch and dinner meals 12

If both preprandial and postprandial blood glucose are high four injection per day regimen  0.7 U/kg up to week 18  0.8 U/kg for weeks 18 to 26  0.9 U/kg for weeks 26 to 36  1.0 U/kg for weeks 36 to term 13

 In a morbidly obese woman, the initial doses of insulin may need to be increased to 1.5 to 2.0 units/kg to overcome the combined insulin resistance of pregnancy and obesity 14

 insulin is divided :  45% as NPH insulin (30% before breakfast and 15% bedtime)  55% as preprandial regular insulin (22% before breakfast, 16.5% before lunch, and 16.5% before dinner) 15

 A four-times daily regimen improved glycemic control and perinatal outcome compared to a twice- daily regimen 16

 Based upon frequent SMBG  4 or more glucose measurements each day are needed to optimize therapy and ensure a smooth increase of insulin as insulin requirements increase with pregnancy progression.  Twin gestations have an approximate doubling of the insulin requirement throughout pregnancy 17

 ADA recommendations FPG <95 mg/dl  1hr pp < 140 mg/dl  2hr pp < 120 mg/dl 18

 Acute hypoglycemia remote from meal or snack time  treated by 10 to 20 gr of carbohydrate immediately  also use a correction factor of one unit of rapid-acting insulin lowers blood glucose by 25 mg/dL 19

 For glucose <50 mg/dL, subtract two units of regular insulin from the dose of insulin given before the meal  for glucose 50 to 75 mg/dL, we subtract one unit from the dose of insulin given before the meal 20

 for glucose 75 to 100 mg/dL do not change insulin dose  for glucose 100 to 125 mg/dL add one unit regular insulin to the dose of insulin given before the meal  for glucose 100 to 150 mg/dL, add two units regular insulin to the dose of insulin given before the meal 21

 insulin pumps are expensive and  Do not clearly provide a benefit in the setting of GDM 22

 The three rapid acting insulin analogs (lispro, aspart, glulisine) are comparable in immunogenicity to human Regular insulin, but only lispro and aspart have been investigated in pregnancy and shown to have acceptable safety profiles, minimal transfer across the placenta, and no evidence of teratogenesis 23

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 lispro and aspart insulin analogs both improve postprandial excursions compared to human Regular insulin and are associated with lower risk of delayed postprandial hypoglycemia 25

 L ong-acting insulin analogs (insulin glargine, insulin detemir) have not been studied extensively in pregnancy  use human NPH insulin as part of a multiple injection regimen in pregnant women  Lente insulins are not recommended due to variability of effect 26

 Insulin is required during the latent phase of labor  SQ or IV insulin infusion with a goal : blood glucose mg/dL  One method :1-3 U/h  N/S may be sufficient to maintain euglycemia when labor is anticipated 27

 active labor : insulin resistance rapidly decreases and insulin requirements fall rapidly  Thus, continuing insulin therapy is likely to lead to hypoglycemia  To prevent this, glucose should be infused at a rate of 2.55 mg/kg per min  Capillary blood glucose : q1h  glucose infusion should be doubled for the next hour if the blood glucose value is < 60 mg/dL 28

 bedtime NPH insulin dose may be given safely at the night of C/S  Dw10 % if PG < 60 mg / dl 29

 If induction procedure is judged likely to be lengthy, 25 – 30 % of morning insulin as NPH may be administered especially if the mother will be allowed meals during early labor  If BG >110 mg / dl :use insulin drip 30

 BG should be measured on the day after delivery to ensure that the mother no longer has hyperglycemia, using criteria established for nonpregnant individuals 31

 The ADA and ACOG do not approve the use of oral anti-hyperglycemic agents during pregnancy  Not been approved by the Unites States FDA 32

 No tolbutamide or chlorpropamide (older sulfonylureas) as therapy of GDM because these drugs cross the placenta and  can cause fetal hyperinsulinemia, which can lead to macrosomia and prolonged neonatal hypoglycemia 33

 In contrast to older sulfonylureas, transplacental passage of glyburide appears to be minimal and is not associated with an excess of neonatal hypoglycemia. Several reports have suggested that glyburide is a safe and effective treatment of GDM, and its use is becoming more prevalent  The fifth International Workshop cautioned its use until there is more research 34

 The only large, randomized study of glyburide therapy in pregnancy included 404 women with mild GDM who were randomly assigned to receive glyburide or insulin  The mean blood glucose concentration during treatment was 105 mg/dL in both groups, and there were no differences in the frequency of macrosomia, neonatal hypoglycemia, and other neonatal morbidity or cord serum insulin concentrations 35

Glyburide Insulin Achieved N BG82%88% LGA infants1213 Macrosomia 7 4 C Section 2324 Hypoglycemia 9 6 Preeclampsia 6 6 Anomalies Langer NEJM 2000

 Glyburide is not recommended as Rx of women with GDM until its safety and efficacy have been more firmly establish e d 37

 no randomized trials evaluating the use of metformin in women with GDM  Several observational series have reported generally good outcomes with use of metformin in pregestational diabetics  A meta-analysis of pregnancy outcome after first trimester metformin did not find risk of major malformations  Until then, metformin should not be used 38

 an alpha glucosidase inhibitor,  is poorly absorbed from the gastrointestinal tract.  studies have suggested efficacy in reducing postprandial glucose excursions in GDM,but with the expected frequency of abdominal cramping  Since a small proportion of this drug may be absorbed systemically, further study should evaluate potential transplacental passage 39

 There are no controlled data available in pregnancy  One study reported that rosiglitazone crossed the human placenta at 10 to 12 weeks gestation, fetal tissue levels were about half of maternal serum levels 40

41 THANKS