1. The document discusses the clinical management of diabetes during pregnancy, including screening, diagnosis, and treatment of gestational and pregestational diabetes. 2. It outlines the risks of hyperglycemia for both mother and fetus, including fetal macrosomia, complications during delivery, and long-term risks like childhood obesity. 3. The management of diabetes during pregnancy involves tight glycemic control through diet, glucose monitoring, and insulin when needed to improve outcomes for both mother and baby.

1. CLINICAL MANAGEMENT OF DIABETES DURING PREGNANCY Antenatal, Intrapartum and Postpartum Perspectives Chukwuma I. Onyeije, M.D. Atlanta Perinatal Associates

2. BACKGROUND: WHAT IS DIABETES? A defect in body energy regulation and utilization Causes: Insulin deficiency Insulin resistance End result: Elevated blood sugar Impact of elevated blood sugar: Pregnancy complications Multi-organ dysfunction Excess mortality

3. Epidemiology and Diagnosis

4. Classification of Diabetes Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183-1197. Genetic defects in b-cell function, Pancreatic disease, Endocrinopathies, Drug- or chemical- induced, and other rare forms Other types Insulin resistance with b-cell dysfunction Gestational Insulin resistance and relative insulin deficiency Type 2 b-cell destruction with lack of insulin Type 1

5. INSULIN PHYSIOLOGY: REGULATION OF BLOOD SUGAR

6. TYPE 1 DIABETES: INSULIN DEFICIENCY  - cell destruction with lack of insulin

7. TYPE 2 DIABETES: INSULIN RESISTANCE Insulin Resistance

8. GESTATIONAL DIABETES: INSULIN DEFICIENCY AND INSULIN RESISTANCE Insulin Resistance Insulin Deficiency

9. Gestational Diabetes Screening High risk Marked obesity Previous unexplained fetal demise Personal history of GDM Glucosuria Strong family history of diabetes Low risk Age <25 years Normal weight before pregnancy Ethnicity with low prevalence No known first degree relatives with diabetes No history of abnormal glucose tolerance No history of poor obstetric outcome

10. Gestational Diabetes Screening Universal screening is advisable 1 hour 50 gm glucose load (GCT)‏ Venous plasma glucose cut-offs 140 mg/dl 135 mg/dl 130 mg/dl

11. SCREENING THRESHOLDS FOR GESTATIONAL DIABETES MELLITUS WITH THE 50-g ORALGLUCOSE-CHALLENGE TEST 90% 20-25% 130 80% 14-18% 140 SENSITIVITY PATIENTS SCREENING POSITIVE THRESHOLD

12. Diagnosis of Gestational Diabetes Three Hour 100 gm glucose tolerance test (GTT)‏ Not necessary if GCT is >200mg/dl on screening Two abnormal values required for the diagnosis of gestational diabetes Currently two diagnostic criteria acceptable

13. Competing Criteria NDDG, 1979 FBS 105 1 hour 190 2 hour 165 3 hour 145 Carpentar and Coustan, 1982 FBS 95 1 hour 180 2 hour 155 3 hour 140

14. Diabetes Trends Among Adults in the U.S. Source: CDC, Behavioral Risk Factor Surveillance System. 1990 2000 1997-1998 No Data Less than 4% 4% to 6% Above 6%

16. Pathophysiology

17. PRINCIPLE DANGERS GESTATIONAL DIABETES: Fetal hyperinsulinemia PREGESTATIONAL DIABETES: Fetal Anomalies

18. Normal Glucose Regulation in Pregnancy The pregnant patient has a tendency to develop HYPOGLYCEMIA between meals Related to fetal demand Placental steroids cause increased tissue insulin resistance They are “DIABETOGENIC” Insulin production INCREASES in normal pregnancy By 30%

19. RECALL: PATHOLOGIC CHANGES IN GDM Insulin Resistance Insulin Deficiency

20. Effects of Hyperglycemia in GDM Fetal hyperglycemia fetal hyperinsulinemia abnormal fetal growth impaired fetal well-being

21. Fetal Hyperinsulinemia Promotes storage of excess nutrients Net Effect: macrosomia Increased catabolism of excess nutrients and increased energy usage Net Effect: Decreased fetal oxygen storage and episodic fetal hypoxia Episodic fetal hypoxia leads to increased catecholamines causing: Fetal hypertension Cardiac remodelling and hypertrophy Increased erythropoietin, RBC’s, hematocrit Poor fetal circulation and hyperbilirubinemia Stillbirth (?)‏

22. The Impact of Fetal Macrosomnia Increased hyperbilirubinemia Increased hypoglycemia Increased acidosis Increased birth trauma Macrosomic children are more likely to develop glucose intolerance in adulthood

23. Congenital Anomalies and Diabetic Control Risk for Congenital Anomalies at various levels of Hemoglobin A1C Critical periods - 3-6 weeks post conception Importance of pre-conceptional metabolic care

24. Congenital Anomalies with Pregestational Diabetes Cardiac defects x18 8.5% CNS defects x16 5.3% Anencephaly x 13 Spina Bifida x 20 All Anomalies x 8 18.4% Background major defects 3-4%

25. Perinatal Risks for All Diabetic Pregnancies: Mortality/Morbidity Miscarriage IUGR Macrosomia Birth Injury Stillbirth

26. Neonatal Risks for All Diabetic Pregnancies: Morbidity and Mortality Polycythemia and hyperviscosity Neonatal hypoglycemia Neonatal hypocalcemia Hyperbilirubinemia Hypertrophic and congestive cardiomyopathy RDS Childhood impaired glucose tolerance

27. Maternal Complications Chronic hypertension Pre-eclampsia Diabetic ketoacidosis Maternal hypoglycemia Maternal trauma Higher C Section rate Retinal disease/renal disease not affected significantly by pregnancy

28. CARE FOR THE PATIENT WITH DIABETES

29. Pre-Pregnancy Management Preconceptional care PRECONCEPTION CARE BEGINS AT THE END OF A PREGNANCY WITH GDM Tight glucose control (HbA1c)‏ Assessment and treatment of associated medical problems Hypertension, Renal disease, Retinal disease Heart disease Folic acid Assessment of family, financial and personal resources to help achieve a successful pregnancy

30. FIRST PERINATAL VISIT or UPON HOSPITALIZATION Review routine prenatal lab tests Baseline 24 hour urinalysis for protein and creatinine clearance Baseline retinal exam - for Type 1 Diabetics EKG - for Type 1 Diabetics Thyroid function tests - for Type 1 Diabetics Hemoglobin A1C Fetal echocardiogram for pregestational diabetics

31. Antepartum Gestational Diabetes Care Dietary advice Glucose monitoring (5 times per day)‏ Insulin therapy if necessary Oral Hypoglycemic agents Frequent visits to monitor glucose control Ultrasound monitoring of fetal growth Mode of Delivery: Based on obstetric issues Timing of Delivery: Based on glucose control

32. What is an ADA diet? Avoidance of large meals with high percentage of simple carbohydrates Three small meals with three snacks are preferred Low glycemic index foods release calories from the gut slowly and improve metabolic control Caloric content: 35 calories/Kg Ideal body weight (or 15 calories/pound IBW)‏ No less than 1800 calories and no more than 2800 calories “ Eyeball Technique” Small patient 1800 calories Medium patient 2200 calories Large patient 2400 calorie

33. What is a “Low” Glycemic Index Glycemic Index (GI): Compares equal quantities of carbohydrate in foods Is a measure of the effect on blood glucose levels over a 2 hr period Provides a measure of carbohydrate quality . Expressed as a percentage Time GI = 30 GI = 100 BGL BGL

34. ‘ Traditional’ starchy foods have a lower GI Barley Legumes/beans Multigrain ‘Specialty’ breads Mueslix Porridge oats 33 30’s 40’s 50’s 50’s Foster-Powell K, Holt SHA, and Brand-Miller JC. International table of glycemic index and glycemic load values:2002. Am J Clin Nutr. 2002; 76 (1): 5-56.

35. “ Sugary” foods have a intermediate-low GI Soft drinks Flavoured milk (low fat) Yogurt (sweetened) Ice cream (low fat) 60’s 34 30-40 50’s Foster-Powell K, Holt SHA, and Brand-Miller JC. International table of glycemic index and glycemic load values:2002. Am J Clin Nutr. 2002; 76 (1): 5-56.

36. Modern starchy foods have a high GI Potatoes Cornflakes Rice crispies Wholegrain bread Crackers Rice (most types)‏ 85 77 85 70 81 83 Foster-Powell K, Holt SHA, and Brand-Miller JC. International table of glycemic index and glycemic load values:2002. Am J Clin Nutr. 2002; 76 (1): 5-56.

37. HOME GLUCOSE MONITORING Fasting and 2 hour post-prandial Pre-meal values only if sliding scale short acting insulin coverage is used Early AM value if hypoglycemia suspected Assure that glucose meter is calibrated

38. INDICATIONS FOR HOSPITALIZATION Persistent nausea and vomiting Significant maternal infection DKA Poor control/compliance Preterm labor

39. Intensive Inpatient Management: The APA Hybrid Protocol For poorly controlled diabetic patients admitted for rapid control. Empiric insulin with the patient’s current standing dose: Targets adequate glycemic control Fasting values: Less than 100 mg/dl 2 hour postparandial values: Less than 120 mg/dl Avoidance of hypoglycemia, ketonuria, and hyperglycemia

40. Intensive Inpatient Management: The APA Hybrid Protocol Begin 2200 to 2400 calorie ADA diet. Obtain fingerstick every 2 hours for 12-24 hours Administer HUMALOG INSULIN for sliding scale Retake blood sugar at 2 hours after EACH sliding dose noted below and repeat sliding scale dose of insulin based on FSG. Adjust Insulin after 24 hours

41. Intensive Inpatient Management: The APA Hybrid Protocol 2 hours 14 Units 220-260 2 hours 16 Units >260 2 hours 12 Units 200-220 2 hours 10 Units 180-200 2 hours 6 Units 161-180 2 hours 4 Units 140-1600 4-6 hours Hold Humalog insulin < 140 Recheck Blood sugar Administer the following dosage of humalog insulin Blood sugar value

42. Patient CH – Before Hybrid Approach Patient CH – After Hybrid Approach

43. Intrapartum management ABSOLUTE REQUIREMENTS: Dextrose containing intravenous fluids Insulin Hourly glucose monitoring Continuous fetal heart rate monitoring Continuous tocodynametry Manage labor as normal

44. THE APA INSULIN DRIP PROTOCOL INTRAVENOUS FLUID MAINLINE: D5W @ 125 cc/hr INSULIN DRIP: Initially Check Fingerstick every hour MIX 100 Units Regular insulin in 500 cc NS (0.2 U/cc)‏ TITRATE INFUSION AS FOLLOWS: After Fingerstick has been between 80-140 x >2 hours, decrease frequency of fingersticks to every 2 hours then every 4 hours. 2.5 U/hr 12.5 cc/hr* FS> 220 2.0 U/hr 10 cc/hr* FS= 181-220 1.5 U/hr 7.5 cc/hr FS= 141-180 1.0 U/hr 5.0 cc/hr FS=101-140 0.5 U/hr 2.5 cc/hr FS= 80-100 0 U/hr Turn off drip FS= <80 Units per hour Drip Rate Fingerstick Value

45. HYPOGLYCEMIA DURING AN INSULIN DRIP For Glucose <60 Turn off Insulin drip for 30 minutes Continue D5W (or D5LR) at 100 – 125 cc/hr Recheck Glucose after 30 minutes If blood glucose on recheck is still <60 Give 25 ml of D50 IV (or 10-12 grams glucose) Recheck Blood Glucose every 30 minutes Restart insulin when glucose >101 mg/dl

46. INSULIN DRIP FOR THE INSULIN RESISTANT PATIENT Method for poorly controlled, morbidly obese or noncompliant patients with gestational diabetes 50% of total daily insulin dosage divided by 24 hours provides initial rate for insulin drip. EXAMPLE: Ms. Jones current insulin regimen AM: 80units NPH 45 units Regular insulin PM: 60 units NPH, 55 units Regular insulin Total daily dosage= 240 units per day. ½ of 240 units = 120 units 120 units / 24 hours = 5 units per hour as initial dosage.

47. Management - Postpartum Use pre pregnancy insulin levels when on diet and monitor. If GDM monitor sugars only Immediate postpartum goal is fingerstick < 200 GDM – Repeat GTT at 6 weeks postpartum GDM - long term risk of NIDDM Contraception

48. THANK YOU !

49. EXTRA SLIDES

51. INSULIN SECRETION Rising blood glucose levels. After the uptake of glucose by the GLUT2 transporter there is Glycolytic phosphorylation of glucose causing A rise in the ATP:ADP ratio, which then Inactivates the potassium channel that Depolarizes the membrane, causing Calcium channel to open up allowing calcium ions to flow inward. The rise in levels of calcium leads to the Release of insulin from their storage granule. 1 2 3 4 5 6 7 8

52. INSULIN ACTION Insulin-mediated glucose uptake begins when Insulin binds to the insulin receptor and Induces a signal transduction cascade which Allows the glucose transporter (GLUT4) to transport glucose into the cell. 1 2 3

53. Diagnosed and Undiagnosed Diabetes in the US: Estimated Cases Among Adults, 1997 Data from Harris, et al. Diabetes Care. 1998;21:518-524. 0 2 4 6 8 10 12 Undiagnosed Diagnosed 10.2 5.4 Millions of Cases

54. Glucose Tolerance Categories: NONPREGNANT Patients Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183-1197. FPG 126 mg/dL 110 mg/dL Impaired Fasting Glucose Normal 2-Hour PG on OGTT 200 mg/dL 140 mg/dL Diabetes Mellitus Impaired Glucose Tolerance Normal Diabetes Mellitus

55. FOLIC ACID All women of reproductive age should consume at least 0.4 mg of folic acid High risk women should consume 4 mg/day This reduces the risk of neural tube defects Newer evidence suggests a lower risk of facial clefting and congenital heart disease as well