���������� � Disclosures Diagnosis and Management of Diabetes in Pregnancy I have nothing to disclose Kirsten Salmeen, MD Assistant Professor, Maternal-Fetal Medicine Department of Obstetrics, Gynecology & Reproductive Sciences Overview Gestational Diabetes Mellitus (GDM) � Physiology “Carbohydrate (glucose) intolerance with onset � Testing or first recognition during pregnancy.” � Pregnancy Outcomes � Previously Unrecognized Type 2 Diabetes � Treatment � Pregnancy Management � Gestational Diabetes � Postpartum Care � �
���������� � Glucose & Insulin Glucose & Insulin – Pregnancy � The fetus uses glucose as its primary substrate, makes its own insulin Bloodstream � Human placental lactogen & progesterone: Carbs Insulin � Decreased gastric motility Receptor Glucose � Reduced insulin receptor sensitivity Glucose � Maternal hyperglycemia � fetal Cell Insulin Causes of Hyperglycemia: hyperglycemia � fetal hyperinsulinemia � � Insufficient Insulin excess fetal growth � Insufficient Insulin Receptor Sensitivity � Glucose >> Insulin Glucose & Insulin – Pregnancy Glucose & Insulin – Pregnancy Pregnancy = “Pancreatic Stress Test” Normal pregnancy: Mean Glucose – Normal Pregnancy Mild fasting hypoglycemia � Fasting: 71 +/- 8 (63 – 79) mg/dL � 1 hr PP: 109 +/- 13 (96 – 122) mg/dL Postprandial hyperglycemia Hyperinsulinemia Hernandez et al. Diabetes Care. 2011;34(7):1660-8. Cunningham et al. Williams Obstetrics, 23rd Edition: http://www.accessmedicine.com. Redrawn from: Phelps et al. Am J Obstet Gynecol. 1981;140(7):730-6. � �
���������� � 33 year-old G2P1 at 11 weeks, BMI = 27, Caucasian, no PMH. Overview First pregnancy: 3 years ago, 50g 1hr glucose test at 26 weeks 138 mg/dL, 3800 g NSVD. Obese aunt with type 2 DM. � Physiology What is your first test? � Testing A. Hemoglobin A1c today � Pregnancy Outcomes B. 50 g 1 hour glucose test today 43% � Treatment C. 75 g 2 hour glucose test today � Pregnancy Management 32% D. 50 g 1 hour glucose test at 24 – 28 weeks � Postpartum Care E. 75 g 2 hour glucose test at 24 – 28 weeks 21% 2% 2% . . . . . . . . . . . . . . . c l l l l 1 g g g g A r r r r u u u u n o o o o i b h h h h o 1 2 1 2 l g g g g g o 0 5 0 5 m 5 7 5 7 e H 2009 County-Level Estimates Testing Goal Diagnosed Diabetes, Adults ≥ 20 Years Identify c hronic hyperglycemia as soon as it exists Percentage 0 - 6.5 6.6 - 8.0 8.1 - 9.4 9.5 - 11.1 > 11.2 www.cdc.gov/diabetes � �
���������� � Testing – Who is High Risk? Testing RR or OR (95% CI) Initial Visit Obese (BMI ≥ 30) 2.90 (2.15 – 3.91) History of GDM 13.2 (12.0 – 14.6) 1 st Degree Family History T2 DM ~ 1.5 – 3.0 High-Risk for Average-Risk for Glucose Age 35 – 39 Years 1.25 (0.99 – 1.58) Glucose Intolerance Intolerance Age ≥ 40 Years 2.24 (1.26 – 3.98) Ethnicity: 24-28 Weeks: First Visit: African American 1.75 (0.95 – 3.23) A1c 50 g 1 Hr Glucose Test � � Hispanic 1.45 (0.87 – 2.41) 75 g 2 Hr Glucose Test 50 g 1 Hr Glucose Test � � Asian/PI 2.32 (1.52 – 3.54) 75 g 2 Hr Glucose Test � Prior LGA Baby Solomon C et al. JAMA 1997;278:1078-83; Kim et al. Am J Obstet Gynecol 2009;201:576.e1-6; Getahun D et al. Am J Obstet Gynecol. 2010;203:467.e1-6 First Visit Testing – A1c First Visit Testing – Diagnosing T2DM � A1c ≥ 6.5% A1c ≥ 6.5 � DM2 Diagnosing Type 2 DM: A1c 5.7 – 6.5 � Glucose Intolerance � Fasting plasma glucose ≥ 126 mg/dL (8-hour fast) A1c < 5.7 � Normal � 2-h plasma glucose ≥ 200 mg/dL following a 75 g Average HbA1c Values Non-Diabetic Women glucose load Non- 1 st Trimester 2 nd Trimester 3 rd Trimester � Random blood glucose ≥ 200 mg/dL with Pregnant HbA1c % 4.8 – 5.5 (5.2) 4.3 – 5.4 (5.0) 4.4 – 5.4 (4.9) 4.7 – 5.7 (5.1) symptoms of hyperglycemia http://www.diabetes.org/diabetes-basics/diagnosis/?loc=DropDownDB-diagnosis O’Connor et al. Clin Chem Lab Med 2012;50(5):905-9. � �
���������� � Testing for GDM Testing for GDM – Two Step Approach � 1960s: Maternal risk for diabetes long-term Step 1 (screen): Non-Fasting 50 g 1 hr glucose test � ≥ 130 mg/dL � 23% screen positive � 2000s: Linear relationship between maternal � ≥ 140 mg/dL � 14% screen positive glycemia and pregnancy outcomes Step 2 (diagnose): Fasting 100 g 3 hr glucose test ≥ 2 abnormal values � positive � Fasting 1 hr 2 hr 3 hr GDM (mg/dL) (mg/dL) (mg/dL) (mg/dL) Prevalence National Diabetes 105 190 165 145 3-4% Data Group Carpenter-Coustan 95 180 155 140 5-7% Criteria Testing for GDM – One Step Approach � Fasting 75 g 2 hr glucose test Conclusion: 2 step approach � ≥ 1 abnormal value � positive Concerns raised: � GDM prevalence ~ 20% � Lack of evidence that more aggressive diagnosis/treatment has benefit � Cost � Resources � Maternal Anxiety � Overtreatment (cesarean rates) IADPSG Consensus Panel. Diabetes Care. 2010;33(3):676-82. VanDorsten et al. NIH Consens State Sci Statements. 2013;29(1):1-30. � �
���������� � What We Do How to Test? High Risk: 1 st Visit Low Risk: 24 – 28 Weeks It depends: 50 g 1 hr Consider: 50 g 1 hr < 140 mg/dL � Patient population A1c FBG � Likelihood of follow-up 75 g 2 hr 50 g 1 hr > 140 mg/dL � Resources Low Risk: Done � Future studies High Risk: Repeat 24 – 28 Weeks 100 g 3 hr Type 2 DM FBG ≥ 95 1 abnormal ≥ 2 abnormals 1 hr ≥ 180 2 hr ≥ 155 Abnormal Glucose Tolerance 3 hr ≥ 140 GDM Overview Pregnancy Outcomes in GDM � Physiology Among your patients with GDM, which adverse outcome do you worry about the most? � Testing � Pregnancy Outcomes A. Shoulder dystocia B. IUFD 55% � Treatment C. Pre-eclampsia � Pregnancy Management D. Neonatal hypoglycemia � Postpartum Care 26% 15% 4% D a . . . . . F s i . o U p g t o s I m y p a y d l c h r e e a l d - e t l r a u P n o o h e S N � �
���������� � Does hyperglycemia without overt diabetes Pregnancy Outcomes in GDM during pregnancy increase risk of adverse pregnancy outcomes? Approximate Overall % Relative Risk/Odds Ratio Macrosomia 20 RR ~1.4 Pre-Eclampsia 15 RR ~1.7 Cesarean Section Varies RR ~ 1.2 Shoulder Dystocia 3-5 OR ~ 1.2 � Blinded study of ~25,000 women at 15 centers, 9 countries IUFD ~ 0.05 RR ~ 2 � Primary predictor: Levels of hyperglycemia � Primary outcomes: birthweight > 90%ile, primary CD, neonatal hypoglycemia, cord-blood C-peptide level > 90%ile HAPO Study Cooperative Research Group. N Engl J Med. 2008;358(19):1991-2002. Schmidt M et al. Diabetes Care. 2001;24(7):1151-5. Wendland E et al. BMC Pregnancy Childbirth. 2012;31(12):23-36. HAPO Study Cooperative Research Group. N Engl J Med. 2008;358(19):1991-2002. HAPO Results HAPO Results Level Fast 1 hr 2 hr 1 < 75 ≤ 100 ≤ 90 (~88 mg/dL) (134.5 mg/dL) (165 mg/dL) 2 75-79 106-132 91-108 3 80-84 133-155 109-125 4 85-89 156-171 126-139 5 90-94 172-193 140-157 6 95-99 194-211 158-177 7 ≥ 100 ≥ 212 ≥ 178 HAPO Study Cooperative Research Group. N Engl J Med. 2008;358(19):1991-2002. HAPO Study Cooperative Research Group. N Engl J Med. 2008;358(19):1991-2002. � �
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