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1N THE NAME OF GOD

1N THE NAME OF GOD. INSULIN THERAPY FOR GDM. SH.ARBABI, M.D Endocrinology Center 18-OCT-2007. INDICATIONS. Approximately 15 percent of women with GDM are placed on insulin therapy With diet , 75 - 80 percent of women with GDM will achieve normoglycemia

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1N THE NAME OF GOD

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  1. 1N THE NAME OF GOD

  2. INSULIN THERAPY FOR GDM SH.ARBABI, M.D Endocrinology Center 18-OCT-2007

  3. INDICATIONS • Approximately15 percentof women with GDM are placed on insulin therapy • With diet , 75 - 80 percent of women with GDM will achieve normoglycemia • main purpose of drug intervention at these levels is to minimize the incidence of macrosomia

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

  5. Caloric intake • BMI < 22 40 KCAL/Kg • BMI(22-27) 3O “ • BMI(27-29) 24 “ • BMI > 30 (12-15) “

  6. Caloric intake • Carbohydrate 40% • Protein 20% • Fat 40% • 75-80% will achieve normoglycemia

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

  8. American college of obstetricions and gynecologists • FBS >95mg/dL • 1hpp>130 to 140 mg/dL • 2hpp>120 mg/dL

  9. American Diabetes Association • FBS >1O5mg/dl • 1hpp>155 mg/dl • 2hpp>130 mg/dl

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

  11. Calculation of dose • 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

  12. Calculation of dose • If postprandial BS are high: regular insulin or insulin lisprobefore meals • 1.5 U per 10 gr CHO in the breakfast meal • 1 U per 10 gr CHO in the lunch and dinner meals

  13. Calculation of dose 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

  14. Calculation of dose • In a morbidly obesewoman, 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

  15. INSULIN • insulin is divided : • 45% as NPH insulin(30% before breakfast and 15% bedtime) • 55% as preprandial regularinsulin (22% before breakfast, 16.5% before lunch, and 16.5% before dinner)

  16. INSULIN • A four-times daily regimen improved glycemic control and perinatal outcomecompared to atwice-dailyregimen

  17. Titration of insulin dose • Based upon frequent SMBG • 4 or more glucosemeasurementseach day are needed to optimize therapy and ensure a smooth increase of insulin as insulin requirements increase with pregnancy progression. • Twin gestationshave an approximate doubling of the insulin requirement throughout pregnancy

  18. Goals • ADA recommendations FPG <95 mg/dl • 1hr pp < 140 mg/dl • 2hr pp < 120 mg/dl

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

  20. Acute hypoglycemia • 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

  21. Titration of insulin dose • for glucose 75 to 100 mg/dLdo not change insulin dose • for glucose 100 to 125 mg/dLadd 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

  22. Not recommended use of insulin pumps • insulin pumpsare expensive and • Donot clearly provide a benefit in the setting of GDM

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

  24. Type of insulin • lispro and aspartinsulin analogs both improve postprandial excursions compared to human Regular insulin and are associated with lower risk of delayed postprandial hypoglycemia

  25. Type of insulin • Long-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 • Lenteinsulins are not recommendeddue to variability of effect

  26. INTRAPARTUM MANAGEMENTSpontaneouslabor • Insulin is required during the latent phase of labor • SQ or IV insulin infusion with a goal : blood glucose 70 - 90 mg/dL • One method :1-3 U/h • N/S may be sufficient to maintain euglycemia when labor is anticipated

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

  28. Cesarean delivery • bedtime NPHinsulin dose may be given safely at the night of C/S • Dw10 % if PG < 60 mg / dl

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

  30. postpartum • BG should be measured on the day after delivery to ensure that the mother no longer has hyperglycemia, using criteria established for nonpregnantindividuals

  31. Oral anti-hyperglycemic agents • The ADA and ACOGdo not approve the use of oral anti-hyperglycemic agents during pregnancy • Not been approved by the Unites States FDA

  32. Tolbutamide and chlorpropamide • No tolbutamideor chlorpropamide(older sulfonylureas)as therapy of GDM because these drugs cross the placenta and • can cause fetal hyperinsulinemia, which can lead to macrosomiaand prolonged neonatal hypoglycemia

  33. Glyburide • In contrast to older sulfonylureas, transplacental passage of glyburideappears 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. Glyburide • 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/dLin both groups, and there were no differences in the frequency ofmacrosomia, neonatal hypoglycemia, and other neonatal morbidity or cord serum insulin concentrations

  35. OralHypoglycemic agents GlyburideInsulin Achieved N BG 82% 88% LGA infants 12 13 Macrosomia 7 4 C Section 23 24 Hypoglycemia 9 6 Preeclampsia 6 6 Anomalies 2 2 Langer NEJM 2000

  36. Glyburide • Glyburide is not recommended as Rx of women with GDM until its safety and efficacy have been more firmly established

  37.  Metformin • 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, metforminshould not be used

  38. Acarbose • 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. Thiazolidinediones, glinides, and GLP-1 • 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. THANKS

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