Current Recommendations Regarding Gestational Diabetes

1. Current Recommendations Regarding Gestational Diabetes By Brandon Ernst UNMC PharmD Candidate 2007 Friday, January 26

2. Objectives for Today • Define gestational diabetes mellitus (GDM) • Indicate possible adverse effects of GDM • Discuss diagnosing GDM • Evaluate monitoring and treatment possibilities • Reassess mother and offspring postpartum • Briefly discuss the results of the Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS)

3. What is Gestational Diabetes?1 • Gestational Diabetes Mellitus (GDM) is glucose intolerance usually recognized during pregnancy • GDM is thought to occur in about 7% of all pregnancies • Hispanic, Native, African, Asian-Americans, and Pacific Islanders are at highest risk

4. Why may GDM occur? The Thought is that:2 • The placenta supports the fetus as it grows by providing hormones for development • These hormones block the action of the mother’s insulin, causing insulin resistance (3x more insulin) • Mother’s body is unable to lower BGL, causing hyperglycemia • The high BGLs remain in the blood stream, cross the placenta, and cause the fetus’s pancreas to produce more insulin to regulate its own hyperglycemic environment • Therefore, leading to possible adverse effects

5. Possible Problems in GDM2 • As the baby continues in this high glycemic environment: • Higher glucose gives more energy than needed for growth, causing fat storage • Macrosomia (large body size) increases the risk of damage to shoulders and limbs during delivery • Increased pancreas/insulin use in baby may cause low BGL and breathing problems at birth • Cesarean delivery • Risk of children developing obesity and adults with type 2 diabetes • Jaundice, polycythemia, and hypocalcemia at birth

6. Possible Problems in GDM2 • The mother’s possible complications include: • Increased chance of cesarean delivery • Increased frequency of maternal hypertensive disorders • Increase risk of developing diabetes after pregnancy, typically type 2

7. Diagnosing GDM3 • Risk assessment should always be done at first prenatal visit, especially with: • Obese patients • Personal history of GDM • Glycosuria • Strong family history • High risk ethnic groups

8. Diagnosing GDM3 • All women, unless low risk, should be tested for GDM at 24-28 weeks. • Low risk must meet all criteria: • <25 y.o. • Normal weight before pregnancy • Member of low ethnic prevalence • No diabetes in first degree relative • No history of abnormal glucose tolerance, and poor birth outcome

9. Diagnosing GDM3,4 • Two Different Approaches One step approach • Perform a diagnostic 75 g or 100 g OGTT without any prior plasma test • This may be best for patients that can’t afford more tests or in patients that are already at high risk

10. Diagnosing GDM3,4 • Two Different Approaches Two step approach • Perform screen using 50 g oral glucose load (OGL) and check BGL at 1 hour • If >130 mg/dL at 1 hour, retest for diagnoses using 75 g or 100 g OGTT

11. Diagnosing GDM3 • The OGTT diagnosis criteria • Patient must be above the BGL at the time interval measured • Positive result must be confirmed on a following occasion

12. Monitoring of GDM3,4 • Daily self monitoring of blood glucose (SMBG) is best • Either Pre or Post -prandial testing is best for obtaining levels (according to ACOG and ADA) • Screen urine for glucose, ketones, and proteins • Monitor blood pressure • Monitor for fetal demise when pregnancy goes past term • Check for asymmetric fetal growth using ultrasound

13. Treatment Options in GDM3 • All women should receive diet and nutrition counseling regarding pregnancy • If BMI > 30 kg/m2: • Lower caloric intake to 25 kcal/kg/day • Lower carbohydrate intake to only 25-30% of total calories • Moderate exercise should be done with physician’s consent • Delivery during or before the 38th week is encouraged, as is breast-feeding

14. When to Add Insulin3,4 • If medical nutritional therapy (MNT) fails then add insulin when BGL are:

15. Treatment Options in GDM3,5,6 • Insulin treatment is best for blood glucose control • Human insulin should be used when prescribed, due to lack of analogs studies • NPH or Regular • Humalog is catagory B, and is being used under Dr. supervision

16. Treatment Options in GDM3,5,6 • Oral agents are still questionable • Glyburide (category B), and insulin were compared in a trial and found to be similar in outcomes • Metformin (category B), shows some good evidence toward its use in PCOS. Its currently being studied in GDM and following up with offspring • Glyburide and Metformin are still not FDA approved for GDM

17. Treatment Options in GDM Do not use in pregnancy: • Aspirin (D) • Statins (X) • ACE Inhbitors (D) • ARBs (D)

18. Delivery Time2 • During Labor: • Active labor lowers insulin needs for about 24-72 hours after delivery • After Delivery: • May have better BGL control for a few weeks • Still could have unpredictable BGL swings • Check BGLs more often during this time • Breastfeeding is encouraged • Have snack before or during nursing, and keep something close to treat low BGLs • Drink fluids

19. Reassessing Offspring2 • Following delivery: • Monitor newborn for any of the possible abnormalities discussed earlier • Monitor for development of obesity • Evaluate for any irregularity in glucose tolerance

20. Reassessing Mother3,4 • A mother having GDM: • Has a 50% chance of developing type 2 diabetes • Should be have BGL evaluated at least 6 weeks postpartum • If normoglycemic, then testing should be done every 3 years • If IFG or IGT, then testing should be repeated annually • If FPG ≥ 126mg/dL or 2-hr ≥ 200, then testing should be repeated on a separate occasion for DM diagnosis

21. The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS)7 • Randomized clinical trial • Wanted to determine whether treating women with GDM reduced perinatal complications • One thousand women randomized • Intervention group – 490 women, received dietary advice, BGM, and insulin therapy • Routine group – 510 women • Weeks gestation - 24-34

22. The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) 7 • Primary endpoint • Serious perinatal complications • death, shoulder dystocia, bone fracture, nerve palsy, admit. neonatal nursery, jaundice, induct. of labor, cesarean birth, anxiety, depression, health • Secondary endpoint • Birth weights, large for gestational age, macrosomia, small for gestational age

23. The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) 7 • Primary outcome results (only clinically significant): • Any serious perinatal complication was significantly lower in the treatment group • Number needed to treat for benefit was 34 • Admission to the neonatal nursery was higher in the treatment group, but length of stay was equal • Induction of labor was higher in the treatment group

24. The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) 7 • Secondary outcome results (only clinically significant) • Birth weight was lower in the treatment group • There were higher rates of macrosomia and large for gestational age in the routine group

25. Questions?

26. References • Isley WL, Oki JC. Diabetes Mellitus. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Well BG, Posey LM, eds. Pharmacotherapy: A Pathologic approach. 5th ed. New York, NY: McGraw-Hill; 2002: 1335. • American Diabetes Association web site. Available at: http://www.diabetes.org/home.jsp/. Accessed January 23, 2007. • American Diabetes Association. Gestational Diabetes Mellitus. Diabetes Care 2004;27:suppl 1: S88-S90. • Clinical management guidelines for obstetrician-gynecologists. ACOG practice bulletin no. 30. Washington, D.C.: American College of Obstetricians and Gynecologists, 2001. • American Diabetes Association. Gestational Diabetes Mellitus. Diabetes Care 2006;29:suppl 2: 485. • Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. New Engl J Med 2000;343:1134-1138 (Level 1) • Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med. 2005;352:2477-86.