Diabetes Related Disclosures

Transcription

1 Diabetes Related Disclosures Speakers Bureau Amylin Boehringer Ingelheim Eli Lilly Takeda Classification of Diabetes Diabetes Care January 2011 vol. 34 no. Supplement 1 S11-S61 Type 1 Diabetes Mellitus Autoimmune destruction of b-cells Type 2 Diabetes Mellitus Progressive b-cell dysfunction Peripheral Insulin resistance» Increased hepatic glucose production» Decreased skeletal glucose uptake» Increased Free Fatty Acid Production Secondary Diabetes Gestational Diabetes At risk for Diabetes, IGT, IFGT Type 1 Diabetes Ø Fasting C-Peptide less than 1 mg/ml, fails to double in response to glucagon Ø Autoimmune markers Islet cell antibodies Anti GAD antibodies Anti Insulin antibodies Saint Agnes Diabetes Symposium

2 Sweet Success Saint Agnes Diabetes Symposium, Joseph B Hawkins Jr, MD, FACE, CDE Glucose Fetal Hyperglycemia Free Insulin Placenta IgG bound Insulin Fetal Hypeinsulinemia Fetal / Neonatal / Perinatal Consequences Preexisting diabetes diagnosed and undiagnosed Fetal organogenesis is complete by 6-8 weeks post conception Hyperglycemia & other metabolic abnormalities Teratogenic Increased risk of 1 st trimester abortion HbA1c prior to 13 wks highly associated with fetal outcome Saint Agnes Diabetes Symposium

3 Risks by 1 st Trimester HbA1c HbA1c < SAB 5% 10% 15% 20% 25%+ Major Malformation 2% 4% 8% 15% 25%+ Diagnosis & Treatment Why Identify Gestational Diabetes? GDM carries risks for the mother and neonate. The relationship between carbohydrate intolerance and fetopathy is linear or curvilinear Carbohydrate intolerance is an independent predictor of adverse outcomes macrosomia and related consequences cesarean sections Saint Agnes Diabetes Symposium

4 Why Identify Gestational Diabetes? The Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, a large-scale ( 25,000 pregnant women) multinational epidemiologic study, demonstrated that risk of adverse maternal, fetal, and neonatal outcomes continuously increased as a function of maternal glycemia at weeks, even within ranges previously considered normal for pregnancy. For most complications, there was no threshold for risk American Diabetes Association International Association of Diabetes and Pregnancy Study Groups (IADPSG) Diagnostic cut points for the fasting, 1-h, and 2-h plasma glucose measurements that conveyed an odds ratio for adverse outcomes of at least 1.75 compared with the mean glucose levels in the HAPO study These new criteria will significantly increase the prevalence of GDM, primarily because only one abnormal value, not two, is sufficient to make the diagnosis. Risk of Macrosomia & Hyperglycemic Peaks Blood Glucose one hour after beginning meal (mg/dl) Jovanovic, Am J Obstec Gyn 1991:164, 103 Saint Agnes Diabetes Symposium

5 Screening for Gestational Diabetes Screen pregnant women with risk factors for diabetes at first prenatal visit Screening Criteria for GDM Low Risk: Blood glucose testing not routinely required if all the following characteristics are present: Member of a low prevalence ethnic group No known FH diabetes, Age <25 Weight normal before pregnancy No history of abnormal glucose metabolism No history of poor obstetric outcome Diabetes Care August 1998; Vol. 21, Supplement 2: B1-B168 GDM Screening Criteria Average Risk Screen with 50 gram GTT at wks.» Positive screen = 1 hr plasma glucose > High risk Prior GDM, Obesity, Excessive Wt gain, strong FH diabetes, prior 9 lb. baby or birth difficulty Screen with 50 gram GTT at first prenatal visit. If not diagnosed repeat testing at 24 to 28 wks.. Saint Agnes Diabetes Symposium

6 Screening Thresholds 50 gm Screen No Longer Recommended Diabetes Screening in Pregnancy At the first prenatal visit, you measure the fasting venous plasma glucose, hemoglobin A 1c, or random plasma glucose in either all women or high-risk women only. If the result indicates overt diabetes, provide treatment and follow-up as is standard for a pregnant woman who has pre-gestational diabetes mellitus. If the result is not diagnostic of overt diabetes and the fasting blood glucose level is 92 mg/dl but <126 mg/dl, then GDM should be diagnosed. If the fasting venous plasma glucose is <92 mg/dl, then you should perform a 75-g OGTT at 24 to 28 weeks gestation. GDM Diagnostic Criteria Follow up positive screen with GTT» GTT thresholds (mg/dl) Carpenter/Coustan ADA 100 gm 75 gm Fasting 95 >92 1 hr 180 >180 2 hr 155 >153 3 hr 140 A positive GTT when ONE thresholds are exceeded Saint Agnes Diabetes Symposium

7 Medical Management Medical Nutritional Therapy Diets are designed to minimize post-prandial glucose, balance carbohydrates, fats and protein Self monitoring of glucose Fasting & postprandial Memory meters Insulin if goals not achieved or maintained In all preexisting diabetes Are We ready for pills? Exercise Medical Nutrition Therapy Calorie requirements during pregnancy are increased by about 300 kcal above basal daily needs in non-pregnant women. Calorie allotment is based upon ideal body weight: 30 to 35 kcal per kg weight per day if BMI 22 to kcal per kg weight per day in overweight women (BMI 27 to 29). 12 to 15 kcal per kg weight per day for obese women (BMI >30). 30 to 40 kcal per kg weight per day in women who are less than BMI 22. Obesity can cause excessive fetal growth, independent of diabetes Meal Content and distribution Carbohydrate intake be restricted to 35 to 40 percent of calories, Remainder divided between protein (about 20 percent) and fat (about 40 percent, primarily unsaturated fats) Noncaloric sweeteners, such as aspartame, may be used in moderation Plasma Glucose Normally Maintained in Narrow Range Plasma Glucose, mg/dl Data from Polonsky KS, et al. N Engl J Med. 1988;318: Diabetic Control B L D 2 AM 6 AM 10 AM 2 PM 6 PM 10 PM Time of Day Saint Agnes Diabetes Symposium

8 Glucose Management Goals (SMBG) Glucose mg/dl Jovanovic ACOG ADA SAMC Fasting < 90 <95 <110 < 90 Pre-Meal <100 <100 <100 1 hr PP <120 <140 <155 <130 2 hr PP <120 Insulin Preparations Meal Insulin Rapid acting Short acting Basal Insulin Intermediate acting Long acting Pre-Mixed Insulin Regular/ NPH based Lispro/ NPL based Aspart/ NPH based Lispro (Humalog) Aspart (NovoLog) Glulisine (Apidra) Regular (Humulin, Novolin) NPH, (Humulin, Novolin) Ultralente (Humulin) Glargine (Lantus) Deteimir (Leimir) 70/30 (Humulin, Novolin) 50/50 (Humulin) 75/25 (Humalog Mix) 70/30 (Novolog Mix) Insulin Vocabulary Basic insulin dose: the standard dose needed for normal BG, meal, and activity Basal insulin: that amount needed to cover physiologic needs independent of food/carbohydrates Meal insulin: rapid acting insulin needed to metabolize dietary carbohydrates Supplemental insulin: adjustments in basic insulin dose to correct blood glucose Compensatory supplements: an increase or decrease in the basic insulin dose to correct high or low BG Anticipatory supplements: adjustments in the basic insulin dose when a change in meals, activity or health is expected Saint Agnes Diabetes Symposium

9 Joseph B. Hawkins, Jr., MD, FACE Insulin Use in Pregnancy No insulin is FDA approved NPH, used as accepted standard LysPro (Humalog), and AspArt (Novolog) Do not cross placenta Do not induce antibody formation Better post prandial glucose control than Regular Human insulin Glargine (Lantus) : limited data on safety, not recommended without informed consent Saint Agnes Diabetes Symposium, 2011 Joseph B Hawkins Jr, MD, FACE, CDE Optimal Insulin Regimen Breakfast Lunch Supper Bedtime Over night Meal Insulin Insulin Action Curve LisPro (Humalog) Aspart (Novolog) Basal Insulin NPH Insulin Action Time in Hours Saint Agnes Diabetes Symposium, Joseph B Hawkins Jr, MD, FACE, CDE Insulin Delivery Syringes Pens 25, 30, 50, 100 units Sweet Success Saint Agnes Diabetes Symposium, 2011 Saint Agnes Diabetes Symposium 2011 Joseph B Hawkins Jr, MD, FACE, CDE 9

10 Pen Needles Metformin In Pregnancy Used in South Africa for T2DM and GDM for over 30 years (many require treatment with insulin) No prospective randomized trials Small studies in PCOS patients Improved fertility Decreased miscarriage rate in first trimester did not lead to an increased incidence of anomalies Does cross the placenta,fetal levels equal maternal levels A meta-analysis of pregnancy outcome after first trimester exposure to metformin did not find an increased risk of major malformation Metformin versus Insulin for the Treatment of Gestational Diabetes N Engl J Med 2008; 358: Of the 363 women assigned to metformin, 92.6% continued to receive metformin until delivery and 46.3% received supplemental insulin. The rate of the primary composite outcome was 32.0% in the group assigned to metformin and 32.2% in the insulin group (relative risk, 1.00; 95% confidence interval, 0.90 to 1.10). More women in the metformin group than in the insulin group stated that they would choose to receive their assigned treatment again (76.6% vs. 27.2%, P<0.001). The rates of other secondary outcomes did not differ significantly between the groups. There were no serious adverse events associated with the use of metformin. Saint Agnes Diabetes Symposium

11 Metformin during pregnancy N Engl J Med 2008; 358: In conclusion, our findings suggest that metformin, alone or with supplemental insulin, is an effective and safe treatment option for women with gestational diabetes mellitus who meet the usual criteria for starting insulin, and that metformin is more acceptable to women with gestational diabetes mellitus than is insulin. Further follow-up data are needed to establish long-term safety. Glyburide In Pregnancy Lowest placental transfer of any sulfonylurea One case controlled study with no adverse outcomes Many requiring insulin Fetal levels < 5% of maternal levels Data in rats and rabbits revealed that neither glyburide nor glipizide was teratogenic, even when given in large doses Glyburide for the Treatment of Gestational Diabetes a critical appraisal Diabetes Care July 2007 vol. 30 no. Supplement 2 S209-S213 1) the rate of glyburide failure is 20% in most clinical populations, and failure is significantly more likely in patients with fasting glucose levels >115 mg/dl; 2) the rate of neonatal hypoglycemia/ hyperbilirubinemia is possibly increased with the use of glyburide compared with insulin 3) mean maternal fasting and postprandial glucose values appear to be lower with glyburide treatment. Saint Agnes Diabetes Symposium

12 Safety of glyburide for gestational diabetes: a meta-analysis of pregnancy outcomes. Ann Pharmacother Apr;42(4): Epub 2008 Mar 18. Nine studies met the inclusion criteria, including a total of 745 glyburide exposed pregnancies and 637 insulin-exposed pregnancies, with each adverse perinatal outcome reported by 4-7 studies. The use of glyburide was NOT associated with risk of macrosomia, differences in birth weight, differences in gestational age at birth, ICU admission, or increased risk of neonatal hypoglycemia TZD In Pregnancy These drugs are known to cross the placenta. In an in-vivo study looking at rosiglitazone placental transfer, 31 women who were undergoing surgical terminations at 8-12 weeks of gestation were given two 4 mg doses of rosiglitazone. Rosiglitazone crossed the placenta in all women, especially in those over 10 weeks' gestation Rosiglitazone in rats and rabbits did not find the drug to be teratogenic at exposures times that obtained with the MRHD Pioglitazone did show increased post implantation losses at doses times the MRHD Few data are available regarding TZD use in the second and third trimesters of pregnancy. NOT RECOMMENDED DURING PREGNANCY SUMMARY: Key Findings Key factors associated with adverse fetal outcome Maternal Pre pregnancy weight Maternal weight gain Hyperglycemia/diabetes Fetal abdominal circumference Medical Nutrition Therapy is most effective therapy Medications including insulin and possibly glyburide or metformin are useful in regulating hyperglycemia and reducing adverse advents. Saint Agnes Diabetes Symposium

13 Post-Partum Management Sweet Success GDM Postpartum Monitoring Those with GDM are at high risk for developing type 2 diabetes. The lifetime risk ranges from 20 to 70% Monitoring 6-12 wks. Post-partum 2 hr gtt Annual fasting glucose's, with A1c Pre Pregnancy planning include glucose assessment Screen subsequent pregnancies at first prenatal visit and again at 24 weeks if normal Postpartum Glucose Tolerance 75 gram glucose tolerance 6 or more weeks postpartum Normal At Risk DM Baseline < >125 & or or 120 < >199 Saint Agnes Diabetes Symposium

14 Diabetes Prevention Program High risk individuals with impaired glucose tolerance randomly assigned to one of three groups Usual Care Provided information about risk and advise to loose wt and exercise Intensive lifestyle intervention Enrolled in a 16 week lifestyle modification intervention with monthly follow up Metformin Prevention of Diabetes: DPP NEJM; 2002, 346: Cumulative incidence of new diabetes 14% 12% 10% 8% 6% 4% 2% Usual Care 11% 0 Metformin 7.8% RRR 31% NNTT = 13.9 Lifestyle 4.8% RRR 58% NNTT = Years % 7.8% 4.8% Prevention of Diabetes: TriPod Buchanan et al. Diabetes 2002 Sept;51(9): Hispanic Women with previous GDM (N = 233) randomized to PLACEBO or TROGLITAZONE 400mg/day. Median follow up 30 months. Protection related to preservation of beta cell insulin secretory capacity Annual incidence of new diabetes 14% 12% 10% 8% 6% 4% 2% 55% RRR P< % 12.1% Troglitazone Placebo Saint Agnes Diabetes Symposium

15 Summary of Conclusions There is an increased risk of obesity and Diabetes in offspring of mothers with GDM Both LGA and SGA babies are at increased risk or future diabetes There is an increasing risk of progression to diabetes with increasing number of pregnancies with GDM Diabetes Care August 1998; Vol.21, Supplement 2: B1-B168 Summary of Conclusions When diagnosed & treated intensively, the risk of intrauterine fetal death is not greater than that of the general obstetric population The overall frequency & severity of perinatal morbidity are less when GDM is managed intensively than when GDM is not managed intensively Diabetes Care August 1998; Vol. 21, Supplement 2: B1-B168 Saint Agnes Diabetes Symposium

16 Criteria for the diagnosis of diabetes Diabetes Care January 2011 vol. 34 no. Supplement 1 S11-S61 A1C 6.5%.or; FPG 126 mg/dl. Fasting is defined as no caloric intake for at least 8 h. * or; 2-h plasma glucose 200 mg/dl (11.1 mmol/l) during an 75 gm OGTT. * or; In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose 200 mg/dl Summary of Conclusions There is an increased risk of obesity and Diabetes in offspring of mothers with GDM Both LGA and SGA babies are at increased risk or future diabetes There is an increasing risk of progression to diabetes with increasing number of pregnancies with GDM Diabetes Care August 1998; Vol.21, Supplement 2: B1-B168 DETECTION AND DIAGNOSIS OF GESTATIONAL DIABETES MELLITUS Diabetes Care January 2011 vol. 34 no. Supplement 1 S11-S61 Screen for undiagnosed type 2 diabetes at the first prenatal visit in those with risk factors In pregnant women not known to have diabetes, screen for GDM at weeks of gestation, using a 75-g 2-h OGTT Screen women with GDM for persistent diabetes 6 12 weeks postpartum. Women with a history of GDM should have lifelong screening for the development of diabetes or prediabetes at least every 3 years. Saint Agnes Diabetes Symposium

17 Questions? Saint Agnes Diabetes Symposium