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Normal physiology of pregnancy First trimester-Increased insulin sensitivity. Late 2 nd and 3 rd trimester insulin resistance possible associated with.

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Presentation on theme: "Normal physiology of pregnancy First trimester-Increased insulin sensitivity. Late 2 nd and 3 rd trimester insulin resistance possible associated with."— Presentation transcript:

1 Normal physiology of pregnancy First trimester-Increased insulin sensitivity. Late 2 nd and 3 rd trimester insulin resistance possible associated with increasing levels of unknown placental hormone(s) which correlate(s) with placental mass.

2 Pathophysiology of GDM Insulin resistance Reduced insulin secretion GDM is characterized by baseline preconception:

3 Low risk- no screening? No longer! Low risk ethnic group ( European American) No Family Hx of DM2 Age <25 Weight normal before pregnancy No hx of abnormal glucose metabolism No hx of poor obstetrical outcome Normal maternal birth weight

4 High Risk Obesity Previous history of GDM Glycosuria Strong family hx of DM (1 st degree relative) Impaired OGTT or IFG Previous baby with > 9 lb birth wt.

5 Diagnostic OGTT (2 abnormal values)???-  HAPO 100gm OGTT criteria O’Sullivan whole blood mg / dl NDDG conversion Plasma mg/dl Carpenter & Coustan Plasma mg/dl Fasting9010595 1 hour165190180 2 hour145165155 3 hour125145140

6 HAPO 23,316 women 75 gm OGTT at 24-32 weeks: fasting, 1hr, and 2 hr glucose obtained Results unblinded and excluded if 2hr >200 mg/dl or if fasting > 105 mg/dl, any 160 mg/dl Only those that stayed blinded and did not undergo further testing were analyzed NEJM 2008:358:1991-2002

7 HAPO Diagnostic GDM Guidelines 1 step testing 2 hour 75 gram GTT Only 1 abnormal value required Fasting 92 mg/dl (5.1 mmol/L) 1 Hour 180 mg/dl (10 mmol/L) 2 Hour 153 mg/dl (8.5 mmol/L) Guidelines based on outcomes ie macrosomia, cord C peptide, preeclampsia etc Diabetes Care 2010; 33:676-682

8 Maternal Glucose vs Primary Outcomes Copyright 2009 ADA. Published online at http://care.diabetesjournals.org/cgi/content/full/dc09-1848/DC1.http://care.diabetesjournals.org/cgi/content/full/dc09-1848/DC1

9 Maternal 1 hr Glucose vs Primary Outcomes Copyright 2009 ADA. Published online at http://care.diabetesjournals.org/cgi/content/full/dc09-1848/DC1.http://care.diabetesjournals.org/cgi/content/full/dc09-1848/DC1

10 Maternal 2 hr Glucose vs Primary Outcomes Copyright 2009 ADA. Published online at http://care.diabetesjournals.org/cgi/content/full/dc09-1848/DC1.http://care.diabetesjournals.org/cgi/content/full/dc09-1848/DC1

11 All HAPO Outcomes- normal vs 1 abnormal glucose Copyright 2009 ADA. Published online at http://care.diabetesjournals.org/cgi/content/full/dc09-1848/DC1.http://care.diabetesjournals.org/cgi/content/full/dc09-1848/DC1

12 Treatment of Mild GDM Landon et al 2009; 361:1339-48 Study group 958 women in 24 th to 31 st week gestation. Inclusion criteria- Fasting glucose 180, or 2 hr >155 or 3 hr >140 Randomization- 485 to treatment group and 473 to control group (blinded) Treatment group targets: fasting <95, 2 hr <120 mg/dl

13 Results Landon et al NEJM 2009; 361; 1339-1448 p<0.001, <0.001, 0.003, 0.02, 0.02, 0.01 respectively below Outcome variable Treatment Control Birth wt 3302 gms 3408 gms Birth wt > (4000 g) 5.9 % 14.3 % Fat mass gms 427 464 Cesarean delivery 26.9 % 33.8 % Shoulder dystocia 1.5 % 4.0 % Preeclampsia/G HTN 8.6 % 13.6 %

14 A Comparison of Glyburide and Insulin in Women with GDM Langer, et al. NEJM 2000;343:1134-1138 404 women with GDM Recruited 11-33 weeks gestation Singleton pregnancies Dietary therapy for all subjects 201  Glyburide (2.5-20mg/day; mean 9mg/day) 203  Insulin, TID dosing Blood Glucose Goals: –Testing 7x/day –Mean 90-105 –Fasting 60-90 –Preprandial 80-95 –2 Hr Postprandial <120

15 A Comparison of Glyburide and Insulin in Women with GDM Langer, et al. NEJM 2000;343:1134-1138 82% on Glyburide reached BG goals 88% on Insulin reached BG goals 4% on Glyburide required Insulin No difference in preeclampsia and c-section rates Maternal Hypoglycemia (<40mg/dL) –4 vs 41 (2% vs 20%) in Glyburide treatment vs Insulin 12 random patients –Simultaneous maternal and cord blood levels of Glyburide measured –Maternal concentrations 50-150 ng/ml –Cord concentrations were undetectable

16 Langer, et al. NEJM 2000;343:1134-1138 50% increase in Neonatal hypoglycemia and hyperbilirubinemia though not significant

17 Predicting which patients might have better control on Glyburide Fasting  110 associated with higher failure –Conway et al. J Matern Fetal Neonatal Med 2004;15:51-55 Failure more likely if diagnosed earlier in pregnancy, older age, multiparous, higher mean fasting glucose –Kahn et al. Obstet Gynecol 2006;107:14303-1309 GLT  200 predicted failure –Rochon et al. AJOG 2006;195:1090-1094

18 Metformin vs Insulin for the Treatment of Gestational Diabetes Rowan et al. NEJM 2008;358:2003-2015. 751 women with GDM at 20-33 weeks randomly assigned to open treatment with Metformin (and insulin if needed) or to insulin Primary outcome was a composite of –Neonatal hypoglycemia –Respiratory distress –Need for phototherapy –Birth trauma –5 min Apgar < 7 –Prematurity

19 Metformin vs Insulin for the Treatment of Gestational Diabetes Rowan et al. NEJM 2008;358:2003-2015. Secondary outcomes –Neonatal anthropometric measurements –Maternal glycemic control –Maternal hypertensive complications –Postpartum glucose tolerance –Acceptability of treatment

20 Enrollment of Subjects Rowan JA et al. N Engl J Med 2008;358:2003-2015

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22 Metformin vs Insulin for the Treatment of Gestational Diabetes Rowan et al. NEJM 2008;358:2003-2015.

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