Gestational Diabetes


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  • Type 1 diabetes is an auto-immune disease that develops when the body’s immune system destroys pancreatic beta cells—the only cells in the body that make the hormone insulin that regulates blood glucose. People with type 1 diabetes must take insulin every day either by injection or pump. Inhalable insulin is also available. Type 1 diabetes accounts for 5% to 10% of all diagnosed cases of diabetes and usually affects children and young adults, although the disease can occur at any age. There is no known way to prevent type 1 diabetes. Type 2 diabetes usually begins as insulin resistance—a disorder in which cells do not use insulin properly. As the need for insulin rises, the pancreas gradually loses its ability to produce it. Insulin resistance and abnormal beta cell function may occur long before type 2 diabetes is diagnosed. Type 2 diabetes accounts for about 90% to 95% of all diagnosed cases of diabetes. It is associated with older age, obesity, family history of diabetes, history of gestational diabetes, impaired glucose metabolism, physical inactivity, and race/ethnicity. African Americans, Hispanic/Latino Americans, American Indians, and some Asian Americans and Native Hawaiians and other Pacific Islanders are at particularly high risk for type 2 diabetes and its complications. Although still rare, type 2 diabetes is being diagnosed more frequently in children and adolescents. Reference National Institute of Diabetes and Digestive and Kidney Diseases. National Diabetes Statistics fact sheet: general information and national estimates on diabetes in the United States, 2005. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health, 2005.
  • These maps show the dramatic increase in obesity and diabetes in the United States from 1990 to 2001. This increase is important because obesity is a major risk factor for type 2 diabetes and because about 55% of adults in the U.S. who have diabetes are also obese (CDC). Reference BRFSS, CDC 1990 – 2001. Centers for Disease Control and Prevention. Prevalence of overweight and obesity among adults with diagnosed diabetes--United States, 1988-1994 and 1999-2002. MMWR. 2004;53:1066-1068.
  • (a ‘diabetes gene’ would endow an ability to survive in time of famine – blood glucose would be maintained for longer at a level to allow normal physiologic function of muscle and brain)
  • FBS: 1(<75) 7(>100) 1-Hr: 1(<105) 7(>212) 2-Hr: 1(<90) 7(>178)
  • Gestational Diabetes

    1. 1. Gestational Diabetes Michael Varner MD Maternal-Fetal Medicine University of Utah Health Sciences Center
    2. 2. Gestational Diabetes Outline Trends in Diabetes Physiology / Pathophysiology Definitions / Diagnosis Complications Management
    3. 3. Common Types of Diabetes <ul><li>Type 1 diabetes </li></ul><ul><ul><li>5% to 10% of diagnosed cases of diabetes </li></ul></ul><ul><li>Type 2 diabetes </li></ul><ul><ul><li>90% to 95% diagnosed cases of diabetes </li></ul></ul>NIDDK, National Diabetes Statistics fact sheet. HHS, NIH, 2005.
    4. 4. Type 2 Diabetes <ul><li>Family history </li></ul><ul><li>Age </li></ul><ul><li>Gestational diabetes </li></ul><ul><li>Obesity </li></ul>Risk Factors:
    5. 5. Obesity Trends 1990 2001 Diabetes Trends 1990 2001 BRFSS, 1990- 2001
    6. 6. Changing rates of GDM (1999-2005)* <ul><li>Southern California Kaiser-Permanente data base (175,249 deliveries) </li></ul><ul><li>Pre-existing Diabetes </li></ul><ul><ul><li>0.81%  1.82% (p < 0.001) </li></ul></ul><ul><ul><li>Increases noted in all age-groups and all racial/ethnic groups (but greatest increases in youngest women) </li></ul></ul><ul><li>Gestational Diabetes </li></ul><ul><ul><li>7.5%  7.4% (N.S.) </li></ul></ul>
    7. 7. Diabetes Epidemic <ul><li>The epidemic increase in diabetes in early 21 st century Western societies is almost exclusively an increase in Type 2 diabetes. </li></ul><ul><li>Type 2 diabetes is a disease of lifestyle (and therefore largely preventable). </li></ul>
    8. 8. Gestational Diabetes 􀂄 “Any degree of glucose intolerance with onset or first recognition during pregnancy” 􀁻 7% of all pregnancies 􀁻 More than 200,000 cases annually 􀁻 Range of prevalence 1-14% (higher in non-Caucasians)
    9. 9. Teleology <ul><li>Humans evolved as hunter-gathers </li></ul><ul><li>‘ Thrifty Genotype / Phenotype’ </li></ul><ul><li>Competition between fetus and mother for finite resources </li></ul><ul><li>What would you do if you were the fetus? </li></ul>
    10. 10. ‘Endocrinology of Pregnancy’ <ul><li>The placenta produces larger quantities of more hormones than any other human organ: </li></ul><ul><ul><li>Human placental lactogen </li></ul></ul><ul><ul><li>Estrogen / progesterone </li></ul></ul><ul><li>The majority of its products are released into the maternal circulation to induce changes on the fetuses’ behalf. </li></ul>
    11. 11. Glucose Metabolism in Pregnancy <ul><li>Fetal growth is dependent upon maternal glucose </li></ul><ul><li>Carbohydrates from maternal diet </li></ul><ul><li>Stored glycogen converted to glucose </li></ul><ul><li>High levels of glucose transported by diffusion to the fetus </li></ul><ul><li>Fetal production of insulin </li></ul>
    12. 12. Glucose Metabolism in Pregnancy <ul><li>First Half of Pregnancy (Anabolic) </li></ul><ul><ul><li>Pancreatic beta-cell hyperplasia causes hyperinsulinemia </li></ul></ul><ul><ul><li>Increased uptake and storage of glucose </li></ul></ul><ul><li>Second Half of Pregnancy (Catabolic) </li></ul><ul><ul><li>Placental hormones block glucose receptors and cause insulin resistance </li></ul></ul><ul><ul><ul><li>Increased lipolysis </li></ul></ul></ul><ul><ul><ul><li>Increased gluconeogenesis </li></ul></ul></ul><ul><ul><ul><li>Decreased glycogenesis </li></ul></ul></ul><ul><ul><li>Increased glucose and amino acids for the fetus </li></ul></ul>
    13. 13. Pedersen Hypothesis (1952) <ul><li>Maternal hyperglycemia  </li></ul><ul><li>Fetal hyperglycemia  </li></ul><ul><li>Fetal hyperinsulinemia  </li></ul><ul><li>Excess fetal fat </li></ul>
    14. 15. (Brief) History of GDM <ul><li>Defined by Statistical Criteria </li></ul><ul><ul><li>3-hour 100 gram oral glucose tolerance test </li></ul></ul><ul><ul><li>Abnormal defined as 2 or more values at, or above, two standard deviations above the mean </li></ul></ul><ul><li>Originally described to identify a group of women at increased risk of type 2 diabetes </li></ul><ul><li>Later identified as a group at increased risk of pregnancy complications (Pedersen Hypothesis) </li></ul><ul><li>The debate about the break point between ‘normal’ and ‘abnormal’ continues to this day. </li></ul><ul><li>* O'Sullivan J B, Mahan C M. Criteria for the oral glucose tolerance test in pregnancy. Diabetes 1 964;13:278-85. </li></ul>
    15. 16. Causes of GDM <ul><li>Inadequate insulin production </li></ul><ul><li>Increased insulin resistance </li></ul><ul><li>Or Both!! </li></ul><ul><li>Strong genetic predisposition </li></ul><ul><li>Progressive increased risk until term (but most clinically significant problems are evident by the early third trimester) </li></ul>
    16. 17. GDM Risk Factors: <ul><li>Family history </li></ul><ul><li>Previous child > 9 pounds </li></ul><ul><li>Glycosuria </li></ul><ul><li>Previous stillbirth – fetal anomalies - polyhydramnios </li></ul><ul><li>Maternal age (>30) </li></ul><ul><li>Non-Caucasian </li></ul><ul><li>Obesity </li></ul>
    17. 18. Screening for GDM (24 - 28 weeks) <ul><li>ACOG Recommendations (2001): </li></ul><ul><ul><li>Risk based approach </li></ul></ul><ul><ul><li>States that “...since so few people have no risk factors, a universal screening program may be more practical...” </li></ul></ul><ul><li>United States (50 gram glucola – venous glucose at 1 hour thereafter) </li></ul><ul><ul><li>Threshold = 130 – 140 mg% </li></ul></ul>
    19. 20. Whole Blood versus Plasma 145 125 3-hour 165 145 2-hour 190 170 1-hour 105 90 Fasting Plasma Whole Blood (incl. capillary)
    20. 21. 100 gm Oral GTT Criteria* *All values in mg% of venous blood 140 145 3-hour 155 165 2-hour 180 190 1-hour 95 105 Fasting Carpenter & Coustan NDDG
    21. 22. 3-hr OGTT Testing <ul><li>Should be done after an 8-14 hour fast </li></ul><ul><li>Should be done with patient sitting </li></ul><ul><li>A single abnormal value identifies a group at some increased risk, but does not establish the diagnosis of GDM </li></ul><ul><li>Time of day does affect likelihood of diagnosis </li></ul>
    22. 23. Screening for gestational diabetes (GD): the effect of screening time <ul><li>Time Morning Afternoon </li></ul><ul><li>(0930–1200) (1205–1710) </li></ul><ul><li>Number screened 176 470 </li></ul><ul><li>Age in years (mean ± SD) 31.2 ± 4.7 31.7 ± 5.0 </li></ul><ul><li>Weight (mean ± SD) 59.4 ± 10.5 kg 60.8 kg ± 12.9 kg </li></ul><ul><li>Family history of diabetes 27 24 </li></ul><ul><li>Positive result, 50 gm GTT 30 (17.0%) 146* (31.1%) </li></ul><ul><li>*p < 0.001 </li></ul><ul><li>Med J Aust 1998;169:93-7 </li></ul>
    23. 24. 75 gm 2-Hour OGTT 155 mg% 2-hour 180 mg% 1-hour 95 mg% Fasting
    24. 25. Adverse Pregnancy Outcomes <ul><li>Maternal hyperglycemia – results in fetal hyperinsulinemia </li></ul><ul><li>Infants </li></ul><ul><ul><li>Macrosomia </li></ul></ul><ul><ul><ul><li>Shoulder dystocia </li></ul></ul></ul><ul><ul><ul><li>Operative delivery </li></ul></ul></ul><ul><ul><li>RDS </li></ul></ul><ul><ul><li>Neonatal hypoglycemia / jaundice </li></ul></ul>
    25. 26. Adverse Pregnancy Outcomes <ul><li>Mothers: </li></ul><ul><ul><li>Polyhydramnios </li></ul></ul><ul><ul><li>Birth trauma / operative delivery </li></ul></ul><ul><ul><li>50-60% lifetime risk of developing type 2 diabetes </li></ul></ul>
    26. 27. Treatment Options <ul><li>Diet </li></ul><ul><li>Exercise </li></ul><ul><li>Education </li></ul><ul><li>Medication </li></ul>
    27. 28. Diet Therapy <ul><li>Many women with GDM can control it with diet alone </li></ul><ul><li>May need medication (oral hypoglycemics or insulin) for control </li></ul>
    28. 29. Exercise <ul><li>Same guidelines as for women with pre-gestational diabetes </li></ul><ul><li>Walking and swimming are both good options. </li></ul>
    29. 30. Education - 1 <ul><li>Symptoms </li></ul><ul><li>Role of diet and exercise </li></ul><ul><li>Blood sugar goals </li></ul><ul><li>Technique and frequency for self-monitoring of blood sugars </li></ul><ul><li>How to complete blood sugar logs </li></ul><ul><li>Potential adverse outcomes of uncontrolled blood sugars </li></ul>
    30. 31. Education - 2 <ul><li>Frequency of visits and antepartum testing </li></ul><ul><li>Potential for medication (including increasing dosages) </li></ul><ul><li>Effects of stress and infection on blood glucose levels </li></ul><ul><li>Risks for future diabetes </li></ul><ul><li>Risk reduction strategies </li></ul><ul><li>Need for lifelong follow up </li></ul>
    31. 32. Blood Sugar Monitoring <ul><li>Initially appropriate for those with elevated fasting glucose </li></ul><ul><ul><li>Demonstrate and return-demonstrate equipment </li></ul></ul><ul><ul><li>Calibration and quality control </li></ul></ul><ul><ul><li>Use of lancet and proper techniques </li></ul></ul><ul><li>Women with normal fasting glucose could be monitored at office visits </li></ul>
    32. 33. Medications <ul><li>Oral hypoglycemics </li></ul><ul><li>Insulin </li></ul>
    33. 34. Oral Hypoglycemics <ul><li>Adequate data suggest glyburide does not cross the placenta </li></ul><ul><ul><li>The are no data for other sulfonylureas </li></ul></ul><ul><li>A 10-25% primary failure rate is noted with glyburide </li></ul><ul><ul><li>More likely to occur in women with a BMI > 41 kg/m2 or higher initial fasting plasma glucose (> 110 mg/dL) </li></ul></ul>
    34. 35. Insulin <ul><li>Initiate if: </li></ul><ul><ul><li>FBS > 105 mg% </li></ul></ul><ul><ul><li>Postprandials > 120 mg% </li></ul></ul><ul><li>Usually 2 injections daily </li></ul><ul><li>Emphasize importance of glucose monitoring and record keeping. </li></ul><ul><li>Injection site selection </li></ul><ul><li>Signs, symptoms and treatment of hypoglycemia (including family education) </li></ul>
    35. 36. Fetal Surveillance / Delivery <ul><li>If on medications, same as women with pregestational diabetes </li></ul><ul><li>Not necessary if: </li></ul><ul><ul><li>Diet-controlled </li></ul></ul><ul><ul><li>No evidence of macrosomia or fetal compromise </li></ul></ul>
    36. 37. Postpartum Glucose Testing after GDM* <ul><li>Retrospective cohort study of 344 women with GDM, 2001-2004 </li></ul><ul><li>Only 45% had postpartum glucose testing </li></ul><ul><li>Of those, 36% had persistent abnormal glucose tolerance. </li></ul><ul><li>Recommendations: </li></ul><ul><ul><li>Improve attendance at postpartum visits </li></ul></ul><ul><ul><li>Improve continuity between antepartum and postpartum care </li></ul></ul><ul><li>*Obstetrics & Gynecology 2006;108:1456-1462 </li></ul>
    37. 38. So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy? <ul><li>HAPO </li></ul><ul><li>ACHOIS </li></ul><ul><li>(MFMU GDM) </li></ul>
    38. 39. HAPO (Hyperglycemia And Pregnancy Outcomes*) <ul><li>Followed > 23,000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes. </li></ul><ul><li>Women with FBS > 105 or 2-hr glucoses > 200 were unblinded. </li></ul><ul><li>Followed for BW > 90 th percentile, primary cesarean, neonatal hypoglycemia, cord-blood C-peptide > 90 th percentile. </li></ul>*NEJM 2008;358:1991-2002
    39. 41. HAPO Conclusion <ul><li>Strong, continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels. </li></ul><ul><li>The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated. </li></ul>
    40. 42. ACHOIS (Australian Carbohydrate Intolerance Study) <ul><li>Randomized 1000 women with 2-hr 75 gram glucose values 140-200 to treatment – no treatment (‘normal < 155). </li></ul><ul><li>Treatment group: Fewer serious perinatal complications and lower birth weights but more NICU admissions. </li></ul><ul><li>Number needed to treat to prevent a ‘serious complication’ (death, shoulder dystocia, bone fracture, nerve palsy) was 34. </li></ul><ul><li>No change in cesarean rate. </li></ul>NEJM 2005;352:2477-86
    41. 43. HAPO vs ACHOIS <ul><li>If it takes 43 ACHOIS interventions (in women with GDM) to prevent one ‘serious complication’, how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem? </li></ul><ul><li>(I don’t know for sure, but it will be a lot) </li></ul>
    42. 44. MFMU GDM Trial <ul><li>‘ Mild’ GDM (Normal FBS, elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation. </li></ul><ul><li>Composite outcome of death, birth trauma, neonatal hypoglycemia or jaundice, or elevated cord C-peptide. </li></ul><ul><li>Recruitment ended October 2007 (enrollment = 1889) – last deliveries occurred in March 2008. (Utah was #2 in recruiting) </li></ul><ul><li>Results anticipated for January 2009 SMFM meeting. </li></ul>
    43. 45. Summary <ul><li>GDM requiring medical treatment identifies a group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes. </li></ul><ul><li>Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications, but the threshold for treatment / non-treatment is not yet clear. </li></ul><ul><li>Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle, particularly diet and exercise. </li></ul>