International Diabetes Center Advances in Diabetes and Pregnancy International Diabetes Center Gestational Diabetes • Part 1: Epidemiology, etiology and pathophysiology of diabetes – new classifications/definitions – incidence, prevalence, morbidity and mortality – causal factors associated with the development of GDM – natural history • Part 2: New therapeutic principles and approaches from the perspective of SDM – detecting the underlying defect – determining the natural history – matching therapy to defect • Part 3: After GDM: the insulin resistance syndrome International Diabetes Center Gestational Diabetes Mellitus • Once believed to be a unimportant event in pregnancy • Initially believed to be a predictor of type 2 diabetes, now believed to be early type 2 diabetes • A combination of increased insulin production with decreased utilization due to insulin resistance • Human placental lactogen production further exacerbates insulin resistance • Over nourishment of the fetus through “shunting” • Maternal insulin does not pass placental barrier • Excess fetal growth due in part to over stimulated fetal pancreas • Estimated to complicate 5% of all pregnancies New International Diabetes Center Gestational Diabetes: Epidemiology 0 20,000 40,000 60,000 80,000 100,000 120,000 140,000 160,000 GDM cases undetected morbidity-poor control morbidity-tight control International Diabetes Center Screening and Diagnostic Criteria for GDM SCREENING • 50 gram Glucose Challenge Test – 1 hour > 140 mg/dL (7.8 mmol/L) DIAGNOSIS • 100 gram Oral Glucose Tolerance Test (OGTT) – Fasting > 95 mg/dL (5.3 mmol/L) – 1 hour > 180 mg/dL (10.0 mmol/L) – 2 hour > 155 mg/dL (8.6 mmol/L) – 3 hour > 140 mg/dL (7.8 mmol/L) • 75 gram Oral Glucose Tolerance Test – Fasting > 95 mg/dL (5.3 mmol/L) – 2 hour > 140 mg/dL (7.8 mmol/L) • One abnormal value ? International Diabetes Center Natural History of Gestational Diabetes 0 50 100 150 200 250 300 < 13 <2 7 27 29 31 33 35 37 39-41 post del 50 100 150 Weeks Weeks Insulin Resistance Insulin Level Fasting Glucose Post Meal Glucose At risk for GDM ©2000 International Diabetes Center. All rights reserved ©2000 International Diabetes Center. All rights reserved Glucose Glucose (mg/dL) (mg/dL) % of Normal Function % of Normal Function HPL GDM GCT OGTT International Diabetes Center Insulin Resistance (Due to HPL or Underlying Type 2 Diabetes) Insulin Sensitive Cells Nucleus G G G G G G G G G G G G G G G G G G G G G G Insulin Glucose Insulin Receptor Glucose Transporter (GLUT 4) G HLP G G G G G G G G G G International Diabetes Center Diabetes Therapies: matching action to underlying defect Medical Nutrition Therapy Oral Agents – Insulin Secretegogues • Sulfonylurea- Glyburide Insulin – Bolus/pre-meal insulin (Regular, Lispro, Aspart) – Basal/background insulin (NPH, Lente, Ultralente, Glargine) New International Diabetes Center Medical Nutrition Therapy* • Action – Emphasis on BG control, not weight loss – Carbohydrate counting – Prevention of weight gain in obese women – Increased physical activity • Clinical Indicators – Insulin Deficiency/Insulin Resistance – BMI - no range – BG range <120 mg/dL (6.7 mmol/L) if used as monotherapy – Always used as an adjunct therapy with pharmacological agents • Side effects – None • Precautions and Contraindications – Kidney Disease: low protein diet for macroalbuminuria – Liver Disease: none – Heart Disease: assess fitness before initiating activity program • Pregnancy – Alter diet and activity to promote normal fetal development and avoid fetal and maternal stress *Self-monitoring of blood glucose and urine ketones (R/O starvation) are essential components of MNT International Diabetes Center SDM GDM Master DecisionPath Overview Fasting < 95 mg/dL (5.3 mmol/L) Casual < 120 mg/dL (6.7 mmol/L) Fasting < 95 mg/dL (5.3 mmol/L) Casual < 120 mg/dL (6.7 mmol/L) Medical Nutrition Stage Focus on carbohydrate foods (portions and number/meal) Encourage physical activity/exercise Medical Nutrition Stage Focus on carbohydrate foods (portions and number/meal) Encourage physical activity/exercise 30 mg/dL (1.7 mmol/L) Entry Criteria Therapies Lowers BG [...]... Stage 30 mg/dL 1.7 mmol/L Oral Agent Stage Oral Agent Stage Insulin Deficiency Glyburide 60 mg/dL 3.3 mmol/L International Diabetes Center Insulin • Action – Compensates for diminished beta cell secretion of insulin – Overcomes insulin resistance in peripheral tissue – Suppresses gluconeogenesis • Clinical Indicators – Insulin Deficiency/Insulin Resistance – BMI-no specific range – HbA1c N.A – FPG >95... effects – Hypoglycemia – Weight gain • Precautions and Contraindications – Kidney Disease: none – Liver Disease: none – Heart Disease: none • Pregnancy – Therapy of choice in GDM when FPG is high, when HbA1c >8% or uncertain of type 1 diabetes International Diabetes Center Normal Insulin Secretion Serum insulin (mU/L) Meal Meal Meal 50 40 Bolus insulin needs 30 20 10 Basal Insulin Needs 0 0 2 4 6 8 10 12... mmol/L 60 mg/dL 3.3 mmol/L Insulin Stage Physiologic Insulin Stage 4 RA-RA-RA-N Note: Each stage requires a pre-set target and a timeline to reach that goal Conventional Insulin Stages 2 or 3 >60 mg/dL >3.3 mmol/L GDM, Type 2 Diabetes and Metabolic Syndrome •Is GDM really type 2 diabetes in pregnancy? •Does GDM always lead to type 2 diabetes after pregnancy? International Diabetes Center ... – 180 mg/dL (6.7-10.0 mmol/L) Side effects Precautions and Contraindications • Pregnancy – All other oral agents pass the placental barrier – Weight gain – Hypoglycemia *Label indicates average glucose lowering 60 mg/dL (3.3 mmol/L) International Diabetes Center Insulin Secretagogues: Beta Cell Function Beta cells produce insulin and store it in secretory vesicles Glucose Transporter (Glut 2) G G G...New • Insulin Secretagogues: Glyburide Action • – Release of insulin from pancreas in response to a glucose challenge • • – Kidney Disease: SU-use caution; – Liver Disease: Use caution, not well studied with liver disease – Known hypersensitivity to the drug Clinical Indicators – Insulin Deficiency – *Mean BG 95 mg/dL... Voltage-gated Calcium Channel Ca++ G GG Pyruvate ATP ADP K+ G X Ca++ Potassium Channel K+ K+ Channel Blocked- membrane becomes depolarized International Diabetes Center SDM GDM Master DecisionPath Overview Entry Criteria Fasting Fasting Casual Casual HbA1c HbA1c Fasting Fasting Casual Casual HbA1c HbA1c < 95 mg/dL < 95 mg/dL (5.3 mmol/L) (5.3 mmol/L) < 120 mg/dL < 120 mg/dL (6.7 mmol/L) (6.7 mmol/L) NA NA . International Diabetes Center Advances in Diabetes and Pregnancy International Diabetes Center Gestational Diabetes • Part 1: Epidemiology, etiology and pathophysiology of diabetes – new. OGTT International Diabetes Center Insulin Resistance (Due to HPL or Underlying Type 2 Diabetes) Insulin Sensitive Cells Nucleus G G G G G G G G G G G G G G G G G G G G G G Insulin Glucose Insulin Receptor Glucose. Agents – Insulin Secretegogues • Sulfonylurea- Glyburide Insulin – Bolus/pre-meal insulin (Regular, Lispro, Aspart) – Basal/background insulin (NPH, Lente, Ultralente, Glargine) New International Diabetes