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Fetal outcomes: Comparison Fetal outcomes: Comparison of oral agents with diet of oral agents with diet controlled and insulin controlled and insulin controlled gestational controlled gestational
diabetesdiabetesAmanda Hatton, MDAmanda Hatton, MD
InvestigatorsInvestigators
Amanda Hatton, MDAmanda Hatton, MD
Selman Welt, MDSelman Welt, MD
Samuel Prien, PhDSamuel Prien, PhD
BackgroundBackground Gestational diabetes affects from 1-14% of Gestational diabetes affects from 1-14% of
pregnant motherspregnant mothers11
Levels of diabetogenic placental steroids and Levels of diabetogenic placental steroids and peptide hormones (estrogen, progesterone, peptide hormones (estrogen, progesterone, chorionic sommatomammotrophin) rise chorionic sommatomammotrophin) rise linearly throughout the second and third linearly throughout the second and third trimester resulting in progressively increasing trimester resulting in progressively increasing tissue resistance to insulintissue resistance to insulin22
Maternal insulin resistance requires a Maternal insulin resistance requires a significant increase in pancreatic insulin significant increase in pancreatic insulin production to more than twice non-pregnant production to more than twice non-pregnant levelslevels
Failure to adequately compensate for Failure to adequately compensate for increased demand of insulin production leads increased demand of insulin production leads to maternal hyperglycemia followed by fetal to maternal hyperglycemia followed by fetal hyperglycemiahyperglycemia
Fetal health implicationsFetal health implications Fetal hyperglycemia leads to fetal Fetal hyperglycemia leads to fetal
hyperinsulinemia which has detrimental hyperinsulinemia which has detrimental consequences to fetal growth and well-consequences to fetal growth and well-beingbeing22
Promotes storage of excess nutrients leading to Promotes storage of excess nutrients leading to macrosomiamacrosomia
Drives catabolism of oversupply of fuel, using Drives catabolism of oversupply of fuel, using energy and depleting fetal oxygen storesenergy and depleting fetal oxygen stores
Episodic fetal hypoxia leads to increased Episodic fetal hypoxia leads to increased adrenal catecholamines causing hypertension, adrenal catecholamines causing hypertension, cardiac remodeling, and hypertrophycardiac remodeling, and hypertrophy
Hypoxia also causes stimulation of Hypoxia also causes stimulation of erythropoietin which in turn increases erythropoietin which in turn increases hematocrit level and causes poor circulation and hematocrit level and causes poor circulation and postnatal hyperbilirubinemiapostnatal hyperbilirubinemia
At birth fetal hyperinsulinemia in absence of At birth fetal hyperinsulinemia in absence of maternal glucose supply leads to hypoglycemiamaternal glucose supply leads to hypoglycemia
Treatment of GDMTreatment of GDM Glycemic monitoring, dietary regulation Glycemic monitoring, dietary regulation
and medical therapy are used to control and medical therapy are used to control diabetes and prevent postnatal sequelaediabetes and prevent postnatal sequelae Insulin discovered in 1922, successful Insulin discovered in 1922, successful
management of diabetic pregnancies became management of diabetic pregnancies became possible and the frequency of antepartum fetal possible and the frequency of antepartum fetal death decreased by one halfdeath decreased by one half22
Glycemic control must be instituted early and Glycemic control must be instituted early and aggressively if excellent newborn outcome is aggressively if excellent newborn outcome is to be achieved to be achieved
Oral agents such as acarbose and glyburide Oral agents such as acarbose and glyburide are aimed at augmenting insulin supply, are aimed at augmenting insulin supply, decreasing insulin resistance, and limiting decreasing insulin resistance, and limiting postprandial hypoglycemia postprandial hypoglycemia
These agents have been shown to be an These agents have been shown to be an effective and safe alternative, since they do effective and safe alternative, since they do not significantly cross the placenta in vitronot significantly cross the placenta in vitro33
ObjectivesObjectives To compare fetal outcomes in mothers To compare fetal outcomes in mothers
with gestational diabetes treated with:with gestational diabetes treated with: Diet - ADA diet, weight dependent, 3 meals Diet - ADA diet, weight dependent, 3 meals
and 3 snacksand 3 snacks Oral agentsOral agents
Acarbose - alpha-glucosidase inhibitor, reversibly Acarbose - alpha-glucosidase inhibitor, reversibly inhibits enzymes in the small intestine, delaying inhibits enzymes in the small intestine, delaying cleavage of oligosaccharides and disaccharides to cleavage of oligosaccharides and disaccharides to monosaccharides monosaccharides
Glyburide - sulfonylurea compound, stimulates insulin Glyburide - sulfonylurea compound, stimulates insulin release from the pancreatic beta cells, reduces release from the pancreatic beta cells, reduces glucose output from the liver and also increases glucose output from the liver and also increases insulin sensitivity at peripheral target sites insulin sensitivity at peripheral target sites
Insulin – weight based split mix dose of NPH Insulin – weight based split mix dose of NPH and Novolog, insulin pump therapy, or long and Novolog, insulin pump therapy, or long acting insulin with supplementationacting insulin with supplementation
This study was submitted to the IRB and This study was submitted to the IRB and was found to be exempt from formal IRB was found to be exempt from formal IRB reviewreview
Experimental DesignExperimental Design Retrospective chart reviewRetrospective chart review
Identify mothers seen at Texas Tech Health Identify mothers seen at Texas Tech Health Science Center (Lubbock) with gestational Science Center (Lubbock) with gestational diabetes who were treated and delivered diabetes who were treated and delivered between January, 2005 and January, 2008between January, 2005 and January, 2008
Includes pregestational diabetics and those Includes pregestational diabetics and those diagnosed by random blood sugar >200mg/dL or diagnosed by random blood sugar >200mg/dL or at least two abnormal values on a 3 hour 100g at least two abnormal values on a 3 hour 100g glucose challengeglucose challenge
All patients were provided with diabetic All patients were provided with diabetic education, including nutrition guidance at the education, including nutrition guidance at the onset of their prenatal care in the case of onset of their prenatal care in the case of preexisting diabetes or soon after diagnosispreexisting diabetes or soon after diagnosis
General Treatment General Treatment GuidelinesGuidelines
DietDietFasting or preprandial >100 mg/dL, 20%Fasting or preprandial >100 mg/dL, 20%
Glyburide 5-10mg dailyGlyburide 5-10mg dailyPostprandials >120 mg/dL, 20%Postprandials >120 mg/dL, 20%
Acarbose 25-100mg TID with mealsAcarbose 25-100mg TID with meals
Still uncontrolledStill uncontrolled
InsulinInsulin
*control = fasting/preprandials*control = fasting/preprandials
<90 mg/dL, 80%, postprandial <120 mg/dL, 80%<90 mg/dL, 80%, postprandial <120 mg/dL, 80%
Materials and MethodsMaterials and Methods Review mother’s and infant’s charts to Review mother’s and infant’s charts to
compare outcomes of different treatment compare outcomes of different treatment modalitiesmodalities Class of gestational diabetesClass of gestational diabetes Treatment and changes in treatmentTreatment and changes in treatment Level of controlLevel of control Complications of pregnancyComplications of pregnancy Mode of deliveryMode of delivery Fetal weightFetal weight Delivery complicationsDelivery complications Fetal complications (hypoglycemia, Fetal complications (hypoglycemia,
hyperbilirubinemia, respiratory distress)hyperbilirubinemia, respiratory distress)
Patients diagnosed ≥ 36 weeks gestation Patients diagnosed ≥ 36 weeks gestation will be excludedwill be excluded
Statistical AnalysisStatistical Analysis
Continuous data will be evaluated Continuous data will be evaluated with an analysis of variance (ANOVA)with an analysis of variance (ANOVA)
Discrete data will be evaluated with Discrete data will be evaluated with a Chi-Square or Mann-Whitney U testa Chi-Square or Mann-Whitney U test
ResultsResults
We expect to find similar fetal outcomes We expect to find similar fetal outcomes in diabetic mothers with blood glucose in diabetic mothers with blood glucose levels that are well controlled by diet, levels that are well controlled by diet, oral agents or insulinoral agents or insulin
Thus far we have noted that there are Thus far we have noted that there are no noticeable differences in outcomes no noticeable differences in outcomes pending a greater number of chart pending a greater number of chart reviews and statistical analysisreviews and statistical analysis
ReferencesReferences 1. American College of Obstetrics and 1. American College of Obstetrics and
Gynecologists—Practice Bulletin Number 30 Gynecologists—Practice Bulletin Number 30 Gestational Diabetes, Washington, Gestational Diabetes, Washington, September 2001.September 2001.
2. Moore TR, Creasy RK, Resnik R: Diabetes 2. Moore TR, Creasy RK, Resnik R: Diabetes in Pregnancy. Maternal-Fetal Medicine 53, in Pregnancy. Maternal-Fetal Medicine 53, pp. 964-985. W.B. Saunders Company, pp. 964-985. W.B. Saunders Company, 1999.1999.
3. Klieger C, Pollex E, Koren G. (2008) 3. Klieger C, Pollex E, Koren G. (2008) Treating the mother—protecting the Treating the mother—protecting the unborn: The safety of hypoglycemic drugs unborn: The safety of hypoglycemic drugs of pregnancy. J Mat Fetal Neonatal Med of pregnancy. J Mat Fetal Neonatal Med 21(3), pp. 191-196.21(3), pp. 191-196.