2012-12-4 CIM World Congress

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2012-12-4 CIM World Congress, Case based discussion on a complicated pregnancy of a patient with overt diabetes, hypertension and other problems. This is an Endocrinologist perspective. Two other speakers tackled the OB and Cardiovascular discussions.

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  • Thank you for introducing me\nI would like to thank the organizing committee for inviting me to speak\nI would also like to thank the faculty and staff of cim for their continued dedication to produce excellent physicians that are globally competitive and internationally recognized. \n
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  • Im considering 4 distinct entities on why this patient has multiple miscarriages.\n1.) the age of the patient predisposes her to high risk of difficult pregnancy\n2.) she is obese having a bmi of 33 which is far higher even by american/european standards\n3.) the last 2 problems are related. both have insulin resistance as part of their pathophysiology. for PCOS, this predates the pregnancy.\n4.) GDM can be overt vs recently diagnosed\n\nall factors individually contrite to the morbidity of the patient. combined each one is synergistic to the other. overall, expect the succeeding months to be critical even after our patient gives birth.\n
  • NEJM on miscarriage rate and maternal age is directly related. as a mother ages the miscarriage rate increases. Note that on the left graph we see the decline of fertility beyond the 20s age. It also follows that the incidence of down syndrome and chromosomal abnormalities go up with age.\n
  • Etiology remains unclear. Its metabolic component includes a state of insulin resistance and obesity. No single etiologic factor that can account for the spectrum of abnormalities. \n
  • - acne, alopecia, hirsutism\n- Hormonal imbalances include Increased frequency of release of GNRH, elevated LH to FSH ratio favoring androgen production and Hyperinsulinemia (IGF-1 prime LH stimulated androgen synthesis & insulin decreases SHBG production thus increase androgen bioavailability. \n
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  • treatment of pcos will depend on what you want to achieve.\n\ncentral to its management is weight loss.\n\nclomiphene - block the effects (competitive inhibitor) of estrogen on the hypothalamus increasing GNRH release \n\ngnrh- short half life\n\n
  • glucose crosses the placenta\ninsulin does not cross the placenta\nDuring labor and delivery, maintain maternal blood glucose concentration between 70 and 90 mg/dL \n\n
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  • Criteria for testing for diabetes in asymptomatic adult individuals\n1. Testing should be considered in all adults who are overweight (BMI >25 kg/m2*) and who\nhave one or more additional risk factors:\nc physical inactivity\nc first-degree relative with diabetes\nc high-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American,\nPacific Islander)\nc women who delivered a baby weighing .9 lb or who were diagnosed with GDM\nc hypertension (blood pressure >140/90 mmHg or on therapy for hypertension)\nc HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride level >250 mg/dL\n(2.82 mmol/L)\nc women with PCOS\nc A1C >5.7%, IGT, or IFG on previous testing\nc other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis\nnigricans)\nc history of CVD\n2. In the absence of the above criteria, testing for diabetes should begin at age 45 years\n3. If results are normal, testing should be repeated at least at 3-year intervals, with consideration\nof more-frequent testing depending on initial results (e.g., those with prediabetes should be\ntested yearly) and risk status.\n*At-risk BMI may be lower in some ethnic groups. PCOS, polycystic ovary syndrome.\n
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  • Criteria for testing for diabetes in asymptomatic adult individuals\n1. Testing should be considered in all adults who are overweight (BMI >25 kg/m2*) and who\nhave one or more additional risk factors:\nc physical inactivity\nc first-degree relative with diabetes\nc high-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American,\nPacific Islander)\nc women who delivered a baby weighing .9 lb or who were diagnosed with GDM\nc hypertension (blood pressure >140/90 mmHg or on therapy for hypertension)\nc HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride level >250 mg/dL\n(2.82 mmol/L)\nc women with PCOS\nc A1C >5.7%, IGT, or IFG on previous testing\nc other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis\nnigricans)\nc history of CVD\n2. In the absence of the above criteria, testing for diabetes should begin at age 45 years\n3. If results are normal, testing should be repeated at least at 3-year intervals, with consideration\nof more-frequent testing depending on initial results (e.g., those with prediabetes should be\ntested yearly) and risk status.\n*At-risk BMI may be lower in some ethnic groups. PCOS, polycystic ovary syndrome.\n\n
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  • \nADA and ACOG do not endorse the use of oral anti-hyperglycemic agents during pregnancy and such therapy has not been approved by the Unites States Food and Drug Administration for treatment of GDM \n
  • only lispro and aspart have been investigated in pregnancy \n\nThere are good data supporting the safety and effectiveness of NPH in pregnancy and doses can be adjusted frequently and quickly in response to changing requirements in pregnant women. \n
  • only lispro and aspart have been investigated in pregnancy \n\nThere are good data supporting the safety and effectiveness of NPH in pregnancy and doses can be adjusted frequently and quickly in response to changing requirements in pregnant women. \n
  • only lispro and aspart have been investigated in pregnancy \n\nThere are good data supporting the safety and effectiveness of NPH in pregnancy and doses can be adjusted frequently and quickly in response to changing requirements in pregnant women. \n
  • only lispro and aspart have been investigated in pregnancy \n\nThere are good data supporting the safety and effectiveness of NPH in pregnancy and doses can be adjusted frequently and quickly in response to changing requirements in pregnant women. \n
  • ADA and ACOG do not endorse the use of oral anti-hyperglycemic agents during pregnancy and such therapy has not been approved by the Unites States Food and Drug Administration for treatment of GDM \n\n
  • ADA and ACOG do not endorse the use of oral anti-hyperglycemic agents during pregnancy and such therapy has not been approved by the Unites States Food and Drug Administration for treatment of GDM \n\n
  • ADA and ACOG do not endorse the use of oral anti-hyperglycemic agents during pregnancy and such therapy has not been approved by the Unites States Food and Drug Administration for treatment of GDM \n\n
  • ADA and ACOG do not endorse the use of oral anti-hyperglycemic agents during pregnancy and such therapy has not been approved by the Unites States Food and Drug Administration for treatment of GDM \n\n
  • ADA and ACOG do not endorse the use of oral anti-hyperglycemic agents during pregnancy and such therapy has not been approved by the Unites States Food and Drug Administration for treatment of GDM \n\n
  • ADA and ACOG do not endorse the use of oral anti-hyperglycemic agents during pregnancy and such therapy has not been approved by the Unites States Food and Drug Administration for treatment of GDM \n\n
  • ADA and ACOG do not endorse the use of oral anti-hyperglycemic agents during pregnancy and such therapy has not been approved by the Unites States Food and Drug Administration for treatment of GDM \n\n
  • ADA and ACOG do not endorse the use of oral anti-hyperglycemic agents during pregnancy and such therapy has not been approved by the Unites States Food and Drug Administration for treatment of GDM \n\n
  • ADA and ACOG do not endorse the use of oral anti-hyperglycemic agents during pregnancy and such therapy has not been approved by the Unites States Food and Drug Administration for treatment of GDM \n\n
  • glucose crosses the placenta\ninsulin does not cross the placenta\nDuring labor and delivery, maintain maternal blood glucose concentration between 70 and 90 mg/dL \n\n
  • glucose crosses the placenta\ninsulin does not cross the placenta\nDuring labor and delivery, maintain maternal blood glucose concentration between 70 and 90 mg/dL \n\n
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  • national cholesterol education program / adult treatment panel III\n\n
  • national cholesterol education program / adult treatment panel III\ninternational diabetes federation\n\n
  • 2012-12-4 CIM World Congress

    1. 1. “The Womb & the Heart : Peripartum Events & Potential Cardiovascular Complications” (Endocrine Perspective) Jeremy F. Robles, MD, FPCP, FPSEM 2012 CIM World Congress Cebu, PhilippinesA case based discussion about a complicated pregnancy
    2. 2. Case• 32 yo pregnant patient (18 weeks)• PCOS (on MET & Hormonal meds)• Multiple miscarriage (G3P1021)• BMI 33, melasma & acne breakout• Uncontrolled HPN & Hyperglycemia
    3. 3. Case• Multiple miscarriage (G3P1021) • Maternal Age • Overweight / Obese • PCOS / Insulin Resistance • Gestational / Overt Diabetes
    4. 4. Maternal Age “At 20 years of age , the miscarriage rate is about 10 %. It increases to a high of more than 90 % among women 45 years of age or older.” N Engl J Med 351;19 2004
    5. 5. PCOS Polycystic Ovarian Syndrome• Most common endocrine disorder in women of reproductive age (7-10%)• Complex & Multigenic• Distinct Clinical & Biochemical Features• Metabolic & Reproductive Problems Co-exist• Major cause of Infertility (diagnosis of exclusion)
    6. 6. PCOS Polycystic Ovarian Syndrome• Clinical signs of Hyperandrogenism• Menstrual Irregularities• Polycystic Ovaries• Associated Features • Hypothalamic-Pituitary Abnormalities • Insulin Resistance & Obesity
    7. 7. PCOS Polycystic Ovarian Syndrome• Increased incidence of Miscarriage• 3 - 7 fold risk for developing DM• Increased cardiovascular risks • Hypertension is common • Dyslipidemia, coagulopathy & vascular inflammation have been reported
    8. 8. PCOS Polycystic Ovarian Syndrome• Nonpharmacologic management (wt. loss)• Pharmacologic Treatment • Oligomenorrhea / Amenorrhea • OCP’s, antiandrogen, insulin sensitizers • Infertility • Metformin + Clomiphene (6-9 months) • Gonadotropin stimulation
    9. 9. Treatment of Diabetes in Pregnancy Obesity• Leading Health concern in pregnant women• Independently risk for recurrent pregnancy loss & congenital malformations• 2 fold increased risk for delivering macrosomic infant• Prevalence 10 fold that of Gestational & Pre-gestaional DM Catalano PM. Management of obesity in pregnancy. Obstet Gynecol 2007:109:419-33.
    10. 10. Treatment of Diabetes in Pregnancy Obesity• Increased maternal Risk for: • Hypertensive & Cardiovascular Disease • Nonalcoholic fatty liver disease & Gallbladder Disease • Aspiration Pneumonia, Sleep Apnea & Pulmonary edema• Maternal BMI - strongest predictor of excess neonatal adiposity associated with childhood obesity• Increased Insulin resistance - altered placental function1. Catalano PM. Obstet Gynecol 2007:109:419-33.2. Yogev Y, Catalano PM. Obstet Gynecol Clin N Am 2009;36:285-300.3. Gunderson RP. Obstet Gynecol Clin N Am 2009;36:317032.4. Keely E. Obesity. American College of Physicians 2008, Philadelphia: 209-215.
    11. 11. Treatment of Diabetes in Pregnancy Body Mass Index (BMI)Measurement of body fat based on height & weight that appliesto both men and women between the ages of 18 and 65 years. kg/m2 US Japanese Singaporean low risk Normal 18.5 - 25 18.5 - 22.9 18.5 - 22.9 moderate Overweight 25 - 30 23 - 24.9 23 - 27.4 high risk Obese class 1 ( 30 - 35) over 25 27.5 and above class 2 ( 35 - 40 ) class 3 ( over 40 )
    12. 12. Gestational DiabetesAny degree of glucose intolerance with onset orfirst recognition during pregnancy, whether ornot the condition persisted after pregnancy, andnot excluding the possibility that unrecognizedglucose intolerance may have antedated orbegun concomitantly with the pregnancy.DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012
    13. 13. Gestational Diabetes (Screening) Oral Glucose Glucose Challenge Tolerance Test WHO criteria Test (GCT) (OGTT) IADPSG* (O’ Sullivan test) (Carpenter & Coustan Test)Glucose Load 75 gm 50 gm 100 gm 75 gm Fasting BG < 126 mg/dl --- < 95 mg/dl < 92 mg/dl1 hour Post < 140 mg/dl (80%) --- < 180 mg/dl < 180 mg/dlglucose load <130 mg/dl (90%)2 hours post < 140 mg/dl --- < 155 mg/dl < 153 mg/dlglucose load3 hours post --- --- < 140 mg/dl ---glucose load 1 or more above normal above normal 2 or more values GDM value above values values above normal normal * International Association of Diabetes and Pregnancy Study Groups (IADPSG)
    14. 14. Gestational Diabetes (Screening) Oral Glucose Glucose Challenge Tolerance Test WHO criteria Test (GCT) (OGTT) IADPSG* (O’ Sullivan test) (Carpenter & Coustan Test)Glucose Load 75 gm 50 gm 100 gm 75 gm Fasting BG < 126 mg/dl --- < 95 mg/dl < 92 mg/dl1 hour Post < 140 mg/dl (80%) --- < 180 mg/dl < 180 mg/dlglucose load <130 mg/dl (90%)2 hours post < 140 mg/dl --- < 155 mg/dl < 153 mg/dlglucose load3 hours post --- --- < 140 mg/dl ---glucose load 1 or more above normal above normal 2 or more values GDM value above values values above normal normal * International Association of Diabetes and Pregnancy Study Groups (IADPSG)
    15. 15. Gestational Diabetes (IADPSG)• Umbrella International Organization of regional & national groups focusing on Diabetes & Pregnancy• Pre-gestational Diabetes associated with adverse perinatal outcome • Large for Gestational Age • Excess Fetal Adiposity • High rate of Cesarean Section• Screening, Diagnosis & Treatment - Cost Effective • NICE (UK) ; HAPO Study ; ACHOIS (AUS)
    16. 16. Gestational Diabetes (IADPSG) • Findings: Continuous graded relationship between higher maternal glucose & increase frequency of: • Birth Weight > 90th percentile • Cesarean Section Delivery • Neonatal Hypoglycemia • Cord C-Peptide > 90th Percentile • Preeclampsia • Preterm Delivery • Birth Injury (Shoulder dystocia)DIABETES CARE, VOLUME 33,NUMBER 3, MARCH 2012
    17. 17. Overt Gestational Diabetes (IADPSG) • Distinct group of Pregnant Women characterized by • Increased risk of congenital anomalies in offspring • Increased risk for diabetes complications ( nephropathy & retinopathy ) • Needs rapid treatment & close follow-up throughout pregnancy and beyondDIABETES CARE, VOLUME 33,NUMBER 3, MARCH 2012
    18. 18. Gestational Diabetes (IADPSG) Gestational Diabetes Overt Diabetes ( 1 or more values exceeds threshold) >/= 126 >/= 92 FPG FPG mg/dl mg/dl >/= 6.5 % 1 hour >/= 180 HbA1C (standardized) post-prandial mg/dlRandom Plasma >/= 200 2 hours >/= 153 Glucose mg/dl (confirmed) post- prandial mg/dl First Prenatal Visit 24-28 weeks Gestation Tests FPG, HbA1c, RBG 2 hour 75g OGTT If (+) then treat If (+) then treat Results If normal then re-test Normal if less than threshold 24-28 weeks DIABETES CARE, VOLUME 33,NUMBER 3, MARCH 2012
    19. 19. Gestational Diabetes (IADPSG) Overt Diabetes Gestational Diabetes >/= 126 >/= 92 FPG FPG mg/dl mg/dl 1 hour >/= 180 HbA1C >/= 6.5 % post-prandial mg/dl Random 2 hours >/= 200 >/= 153 Plasma post- mg/dl mg/dl Glucose prandialTotal Incidence of GDM (HAPO Study) was 17.8% with FPG & 1-hour post-prandial glucose identifying most individuals
    20. 20. Diagnosis of Hyperglycemia in Pregnancy • First prenatal Visit • FPG, HbA1C or RBS on all / high risk women • If (+) treat and follow-up • If (-) retest OGTT at 24-28 weeks • 24-28 weeks Gestation • 2 Hour 75-gm OGTT • If (+) treat & follow-up • If (-) then normalDIABETES CARE, VOLUME 33,NUMBER 3, MARCH 2012
    21. 21. Treatment of Diabetes in Pregnancy • Dietary Therapy • Self glucose monitoring • Administration of Insulin
    22. 22. Treatment of Diabetes in Pregnancy Medical Nutrition Therapy• ideal body weight (30 kcal/kg/day)• overweight (22 to 25 kcal/kg/day)• morbidly obese (12 to 14 kcal/kg/day)• underweight (40 kcal/kg/day)• Carbohydrate intake limited to less than 40%• CHON 20% Fats 40%• 3 small-to-moderate sized meals and 2 - 4 snacks
    23. 23. Treatment of Diabetes in Pregnancy Glucose Monitoring• Monitor FBS + 1 hour post meals glucose (start at 1st bite)• Glucose Targets ADA ACOG Fasting </= 95 mg/dl </= 95 mg/dl 1 hr PP </= 140 mg/dl </= 130 mg/dl 2 hrs PP </= 120 mg/dl </= 120 mg/dl• Avoid prolonged fasting ( ketonuria )• Exercise improve glycemic control with increased tissue sensitivity to insulin
    24. 24. Treatment of Diabetes in Pregnancy Peripartum Management• Antiglycemic agents vs Insulin therapy • ADA & ACOG do not endorse OHA’s in pregnancy • Glyburide (conflicting data ) • Metformin ( inadequate glycemic control )• Insulin dose range 0.7 to 2 units/Kg (present pregnant wt.)• Four times per day regimen improved glycemic control• Titrate insulin dose to blood glucose levels
    25. 25. Treatment of Diabetes in Pregnancy Insulin Therapy7:00am noon 7:00pm midnight 7:00am Breakfast Lunch Supper Physiologic insulin secretion
    26. 26. Treatment of Diabetes in Pregnancy Insulin Therapy7:00am noon 7:00pm midnight 7:00am Breakfast Lunch Supper Physiologic insulin secretionRapid Acting Insulin (Lispro, Aspart)
    27. 27. Treatment of Diabetes in Pregnancy Insulin Therapy7:00am noon 7:00pm midnight 7:00am Breakfast Lunch Supper Physiologic insulin secretionRapid Acting Insulin (Lispro, Aspart)
    28. 28. Treatment of Diabetes in Pregnancy Insulin Therapy Isophane Insulin7:00am noon 7:00pm midnight 7:00am Breakfast Lunch Supper Physiologic insulin secretionRapid Acting Insulin (Lispro, Aspart)
    29. 29. Treatment of Diabetes in Pregnancy Insulin Therapy Isophane Insulin7:00am noon 7:00pm midnight 7:00am Breakfast Lunch Supper Physiologic insulin secretionRapid Acting Insulin (Lispro, Aspart)
    30. 30. Treatment of Diabetes in Pregnancy Insulin Therapy Isophane Insulin7:00am noon 7:00pm midnight 7:00am Breakfast Lunch Supper Physiologic insulin secretionRapid Acting Insulin (Lispro, Aspart)
    31. 31. Treatment of Diabetes in Pregnancy Insulin Therapy Isophane Insulin7:00am noon 7:00pm midnight 7:00am Breakfast Lunch Supper Physiologic insulin secretionRapid Acting Insulin (Lispro, Aspart)
    32. 32. Treatment of Diabetes in Pregnancy Peripartum Management• Maternal = fetal hyperglycemia (acidosis & hypoglycemia)• Most GDM are normoglycemic after delivery• 2/3 of GDM will have GDM in a subsequent pregnancy• GDM is predictive of type 1 & 2 DM & CVD• Follow-up 75 gm OGTT 6 to 12 weeks after delivery• Reassessment of glycemic status every 3 years
    33. 33. Hope for the best.Expect the worst.

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