1. Glycemic Control During Labor and Delivery 1

2. Hormonal Changes During Labor and Delivery in Healthy Nondiabetic Women PGE 2 and oxytocin: substantial increase during laborPGE 2 and oxytocin: substantial increase during labor –May be trigger for labor Estradiol, vasoactive intestinal peptide, gastric inhibitory polypeptide (GIP): slight increase during laborEstradiol, vasoactive intestinal peptide, gastric inhibitory polypeptide (GIP): slight increase during labor 17-hydroxyprogesterone: little or no change during labor17-hydroxyprogesterone: little or no change during labor Prolactin: decrease during first stage of labor, then increase during second to third stages and deliveryProlactin: decrease during first stage of labor, then increase during second to third stages and delivery Insulin (and glucose): increase during deliveryInsulin (and glucose): increase during delivery 2 Jovanovic L. Endocr Pract. 2004;10:40-45.

3. Stages of Labor First stage:First stage: –Commences when uterine contractions are of sufficient frequency, intensity, and duration to bring about effacement and dilation of the cervix –Ends when the cervix is fully effaced Second stage:Second stage: –Commences when the cervix is fully effaced –Ends when the infant is delivered Third stage:Third stage: –Commences when the infant is delivered –Ends when the placenta is delivered 3

4. The Deleterious Effect of Hypertonic Glucose Infusions During Labor Takeda Y, et al. Am J Obstet Gynecol. 1966;96:872-877. Romney SL, et al. Am J Obstet Gynecol. 1966;96:698-709. Anderson GG, et al. Obstet Gynecol. 1970;36:405-414. Oakley NW, et al. BMJ. 1972;1:466-469. YearAuthorSubject Glucose Infused Results 1966TakedaDogs25 g Mothers >600 mg/dL Pups >300mg/dL = 100% death Pups <300 mg/dL = fewer dead pups 1966Romney Normal humans 25 g Fetuses >180 mg/dL Bradycardia 1970Anderson Normal humans 25 g No benefit Fetal pH decreased Uterine activity 1972Oakley Humans with gestational diabetes 50 g No benefit Mothers >300 mg/dL Fetal insulin increased >10-fold above normal, leading to fetal hypoglycemia 4

5. The Magnitude of Neonatal Hypoglycemia Inversely Related to Maternal Hyperglycemia at Delivery Jovanovic L, et al. Am J Med. 1983;75:607-612. 0 0 50 100 150 200 250 Maternal Glucose Neonatal Glucose Type 1 DMType 2 DMGestational DM 5

6. No Exogenous Insulin Administration Superior to Any Insulin Infusion During Labor and Delivery YearAuthorGlucose RateInsulin RateGlycemia 1977 West12 g/h1-2 U/h Hypoglycemia in 4 h 1978Yeast5 g/h0.25-2 U/h Hyperglycemia then hypoglycemia 1982Caplan5 g/h0.25-3 U/hSevere hypoglycemia 1982Golde6 g/h0Normal 1983Jovanovic 2.55 mg/kg/min = 10 g/h for 60 kg 0Normal West TE, et al. BMJ. 1977;1:1252-1254. Yeast JD, et al. Am J Obstet Gynecol. 1978;131:861-864. Caplan RH, et al. Diabetes Care. 1982;5:6-10. Golde SH, et al. Am J Obstet Gynecol. 1982;144:556-559. Jovanovic L, et al. Am J Med. 1983;75:607-612. 6

7. Glucose Infusion Rates for Diabetic Women in Active Labor Weight kg Glucose mg/min D 5 NSD 10 NS mL/minmL/hmL/minmL/h 3076.51.5291.20.7645.6 3589.31.78106.80.89 53.4 40102.02.04122.41.02 61.2 45114.82.30138.01.1569.0 50127.52.55153.01.2776.5 55140.32.80168.01.40 84.0 Jovanovic L, et al. Am J Med. 1983;75:607-6l2. Equal to Dextrose 2.55 mg/kg/h 7

8. Jovanovic L, et al. Am J Med. 1983;75:607-6l2. Glucose Infusion Rates for Diabetic Women in Active Labor Weight kg Glucose mg/min D 5 NSD 10 NS mL/minmL/hmL/minmL/h 60153.03.06183.61.53 91.3 65165.83.32199.21.66 99.6 70178.53.56213.61.78 106.8 75191.33.82229.21.91114.6 80204.04.08244.82.04122.4 85216.84.34260.42.17 130.2 Equal to Dextrose 2.55 mg/kg/h 8

9. Glucose Infusion Rates for Diabetic Women in Active Labor Jovanovic L, et al. Am J Med. 1983;75:607-6l2. Weight kg Glucose mg/min D 5 NSD 10 NS mL/minmL/hmL/minmL/h 90229.54.58274.82.29 137.4 95242.34.84290.42.42 145.2 100255.05.10306.02.55 153.0 105267.85.36321.62.68160.8 110280.55.60336.02.80168.0 115293.35.86351.62.93 175.8 120306.06.12367.23.06 183.6 125318.86.38382.83.19 191.4 Equal to Dextrose 2.55 mg/kg/h 9

10. Protocol for Adjusting Intrapartum Intravenous Solutions and Insulin Administration in Labor and Postpartum GlucoseAdjustments ≤70 mg/dLD 10 NS for 10-15 minutes, rate 100 mL/h 71-100 mg/dLD 5 NS/100 mL/h 101-120 mg/dLNS/100 mL/h >121 mg/dLNS plus regular insulin IV or SC per hour as percent of “Big I”* 121-140 mg/dLNS/100 mL/h plus 3% “Big I” >141 mg/dLNS/100 mL/h plus 6% “Big I” “Big I” = Total daily insulin requirement. * At term “Big I” is 1.0 U/kg per day. Thus, 3% of this dose would be 3 units in a 100-kg woman at term. D 5, 5%dextrose; D 10, 10% dextrose; NS, normal saline. Jovanovic L. Endocr Pract. 2004;10:40-45. 10

11. Protocol for Adjusting Intrapartum Intravenous Solutions and Insulin Administration in Labor and Postpartum in Women with T1DM on Insulin Pumps GlucoseAdjustments ≤70 mg/dLD 10 NS for 10-15 minutes, rate 100 mL/h 71-100 mg/dLD 5 NS/100 mL/h 101-120 mg/dLNS/100 mL/h >121 mg/dLNS plus regular insulin IV or SC per hour as percent of “Big I”* 121-140 mg/dLNS/100 mL/h plus 3% “Big I” >141 mg/dLNS/100 mL/h plus 6% “Big I” “Big I” = Total daily insulin requirement. * At term “Big I” is 1.0 U/kg per day. Thus, 3% of this dose would be 3 units in a 100-kg woman at term. D 5, 5%dextrose; D 10, 10% dextrose; NS, normal saline. Jovanovic L. Endocr Pract. 2004;10:40-45. 11