Presentation on theme: "Kirstin Woo, MD Palo Alto Foundation Medical Group May 5, 2009"— Presentation transcript:
1Kirstin Woo, MD Palo Alto Foundation Medical Group May 5, 2009 Diabetes in PregnancyKirstin Woo, MDPalo Alto Foundation Medical GroupMay 5, 2009
2Outline Physiologic changes in pregnancy Diabetes in pregnancy Organ systems affectedMetabolic changes in pregnancyDiabetes in pregnancyClinical implicationsEpidemiology/TypesScreening and DiagnosisManagementFuture directionsNow that we have considered the general differences between glucose metabolism in the pregnant and non-pregnant state, let us move on to the discussion of when glucose metabolism goes awry – diabetes in pregnancy.
3Physiologic changes in pregnancy Cardiovascular systemRespiratory systemGastrointestinal systemUrinary systemEndocrine systemGenital TractSkinPregnancy affects nearly all systems in the bodyI will focus on the cardiovascular, respiratory and GI effects and then move on to the metabolic changes, since that relates more closely to diabetes in pregnancy
4Physiologic changes in pregnancy: Cardiovascular Sodium and water retentionReduced systemic blood pressure (mean 105/60 mmHg in 2nd trimester)Increased cardiac output (30-50% rise)Increased blood volume (total body water increases 40%)Reduced systemic vascular resistance (vasodilitation PLUS high flow, low-resistance circuit of the uteroplacental circulation)Increased maternal heart rate (up beats/min)As a result of increased blood volume and reduced systemic blood pressure, cardiac output increases significantly. In general, the heart is “working harder” through pregnancy, not to mention during labor, which means that women with preexisting heart conditions need to have special consideration when conceiving.
5Physiologic changes in pregnancy: Respiratory Mechanical changesDiaphragm rises 4 cmLess negative intrathoracic pressureNo impairments in diaphragmatic or thoracic muscle motionLung compliance remains unaffectedPhysiologic changesOxygen consumption increases %50% of this increase is required by the uterusProgesterone directly stimulates breathing70% of women experience dyspnea (increased desire to breathe)The change in anatomy, especially later in pregnancy influences the shape and function of the thoracic (chest) cavityWith a smaller volume, there is less negative pressure and therefore the volume inhaled with each breath is decreased. The muscle and lung tissue functions themselves remain the same.
6Physiologic changes in pregnancy: Gastrointestinal MechanicalPressure from growing uterus on stomach reflux/heartburnPressure from growing uterus on lower portion of colon and rectum constipationPhysiologicRelaxation of sphincter muscle between esophagus and stomachProgesterone (a smooth muscle relaxant) causes decreased GI motility and delayed gastric emptying
7Normal glucose metabolism Glucose enters bloodstream from food sourceInsulin aids in storage of glucose as fuel for cellsInsulin resistance is defined as insensitivity of cells to insulin, therefore resulting in increased levels of insulin and glucose in the bloodstreamLet’s talk about the changes in metabolism that occur during pregnancy, specifically carbohydrate metabolism. First of all, normal glucose metabolism is depicted here.Glucose is absorbed from the stomach and small intestine and enters the bloodstream, then is transported to various organs. Insulin, secreted by the pancreas is required to permit entry of the glucose into the cell to be used.
8Metabolic changes in pregnancy Caloric requirement for a pregnant woman is 300 kcal higher than the non-pregnant woman’s basal needsPlacental hormones affect glucose and lipid metabolism to ensure that fetus has ample supply of nutrientsLater in gestation with increased fetal growth, larger fluctuations in glucose and insulin occur as mother oscillates between fed and fasted states (during fasting, glucose is reserved for fetus)
9Metabolic changes in pregnancy Lipid metabolism:Increased lipolysis (preferential use of fat for fuel, in order to preserve glucose and protein)Glucose metabolism:Decreased insulin sensitivityIncreased insulin resistance
10Metabolic changes in pregnancy Increased insulin resistanceDue to hormones secreted by the placenta that are “diabetogenic”:Growth hormoneHuman placental lactogenProgesteroneCorticotropin releasing hormoneTransient maternal hyperglycemia occurs after meals because of increased insulin resistance
11Metabolic changes in pregnancy Relative baseline hypoglycemiaProliferation of pancreatic beta cells (insulin-secreting cells) leads to increased insulin secretionInsulin levels are higher than in pregnant than nonpregnant women in fasting and postprandial statesHypoglycemia between meals and at night because of continuous fetal drawBlood glucose levels are 10-20% lower
12Metabolic changes in pregnancy Lipid metabolismIncreased serum triglyceride (300%) and cholesterol (50%) levelsSpares glucose for fetus, since lipids do not cross the placentaProvides building blocks for increased steroid hormone synthesis
13Outline Physiologic changes in pregnancy Diabetes in pregnancy Organ systems affectedMetabolic changes in pregnancyDiabetes in pregnancyClinical implicationsEpidemiology/TypesScreening and DiagnosisManagementFuture directionsNow that we have considered the general differences between glucose metabolism in the pregnant and non-pregnant state, let us move on to the discussion of when glucose metabolism goes awry – diabetes in pregnancy.
14Diabetes in Pregnancy: Clinical Implications Obstetric complications:Increased incidence of miscarriageCongenital malformationsIncidence 4X higher than in general populationMost significant remaining cause of fetal death is congenital malformationAssociation with hypertensive disorders of pregnancyGestational hypertensionPreeclampsiaIt has long been recognized that poorly controlled diabetes causes a multitude of obstetric complications
15Diabetes in Pregnancy: Clinical implications Shoulder dystociaFetal macrosomia
17Diabetes in Pregnancy: Clinical Implications Fetal macrosomiaDisproportionate amount of adipose tissue concentrated around shoulders and chestRespiratory distress syndromeNeonatal metabolic abnormalities:HypoglycemiaHyperbilirubinemia/jaundiceOrganomegalyPolycythemiaPerinatal mortalityLong term predisposition to childhood obesity and metabolic syndromeOther perinatal complications involve both long and short term exposure to high levels of serum glucose.
18Outline Physiologic changes in pregnancy Diabetes in pregnancy Organ systems affectedMetabolic changes in pregnancyDiabetes in pregnancyClinical implicationsEpidemiology/TypesScreening and DiagnosisManagementFuture directionsNow that we have considered the general differences between glucose metabolism in the pregnant and non-pregnant state, let us move on to the discussion of when glucose metabolism goes awry – diabetes in pregnancy.
19Diabetes in Pregnancy: Epidemiology Preexisting diabetes complicates~1 % of pregnancies in US (>8 million women)154,000 (4%) of all pregnancies are affected by diabetes135,000 (88%) due to GDM12,000 (8%) due to Type 2 DM7,000 (4%) due to Type 1 DM
20Diabetes in Pregnancy: Epidemiology Geographic disparities exist in the state of California with the highest rates of GDM reported in the counties of Alameda, Amador, Colusa, Glenn, Monterey, Santa Clara and Yolo
21Diabetes in Pregnancy: Classification CriterionWhite Classificationgestational diabetes, insulin not requiredA1gestational diabetes, insulin requiredA2age of onset >= 20 years (maturity onset diabetes)B1duration < 10 years, no vascular lesionsB2age of onset years of ageC1duration years, no vascular lesionsC2age of onset < 10 years of ageD1duration >= 20 yearsD2benign retinopathyD3calcified arteries of legsD4calcified arteries of pelvis (no longer sought)EnephropathyFmany failuresGcardiopathyHproliferating retinopathyRrenal transplantTPriscilla White developed this classification system to assess maternal and fetal risk and differentiate between preexisting diabetes and gestational diabetes
22Diabetes in Pregnancy: Types Gestational Diabetes Mellitus (GDM)Type A1: abnormal oral glucose tolerance test (OGTT) but normal blood glucose levels during fasting and 1-2 hours after meals; diet modification is sufficient to control glucose levelsType A2: abnormal OGTT compounded by abnormal glucose levels during fasting and/or after meals; additional therapy with insulin or other medications is requiredPregestational Diabetes MellitusType 1: autoimmune process that destroys pancreatic b cellsType 2 (“lifestyle diabetes”): acquired insulin resistance related to obesity
23Pregestational Diabetes: Types 1 and 2 Type 1 is characterized by lack of insulin (a production problem)Type 2 is characterized by plentiful insulin that is not able to do its job effectively (a function problem – i.e., lack of response, hence the term “insulin resistance”)
24Gestational Diabetes (GDM) Definition:Insulin resistance/ glucose intolerance first diagnosed during pregnancyPrevalence: 1-14% of all pregnanciesIndicates predisposition to later development of Type 2 DiabetesChance of recurrence in future pregnancies:30-84%Within years after delivery, approximately 50% of women who had gestational diabetes will develop type 2 diabetesVaries by ethnicity – in the Hispanic population, up to 50% develop type 2 diabetes within 5 years of diagnosis of gestational diabetesPrevalence is wide-ranging and variable depending on ethnic makeup of the population.Also, patients’ first presentation may be during pregnancy
25GDM: Risk factors Maternal age >25 years Body mass index >25 kg/m2Race/EthnicityLatinaNative AmericanSouth or East Asian, Pacific Island ancestryPersonal/Family history of DMHistory of macrosomia
26Gestational Diabetes (GDM) Risk factors play into increased pre-conception insulin resistanceAdding on insulin resistance of pregnancy because of estrogen/progesterone and placental hormones creates a hyperinsulinemic state
27Outline Physiologic changes in pregnancy Diabetes in pregnancy Organ systems affectedMetabolic changes in pregnancyDiabetes in pregnancyClinical implicationsEpidemiology/TypesScreening and DiagnosisManagementFuture directionsNow that we have considered the general differences between glucose metabolism in the pregnant and non-pregnant state, let us move on to the discussion of when glucose metabolism goes awry – diabetes in pregnancy.
28GDM: Screening Screening test Screening thresholds 50 gm 1-hour glucose challenge test (GCT)Screening thresholds130mg/dL: 90% sensitivity(23% screen positive)140mg/dL: 80% sensitivity(14% screen positive)If patient screens positive, she goes on to take a 3-hour glucose tolerance test (GTT)50 grams of glucola are drunk, followed by a serum measurement of glucose one hour later2/3 of obgyns use 140 cutoff1/3 of obgyns use cutoff
29National Diabetes and Data Group GDM: DiagnosisFasting blood glucose >126mg/dL or random blood glucose >200mg/dL100 gm 3-hour glucose tolerance test(GTT) with 2 or more abnormal valuesCarpenter and CoustanNational Diabetes and Data GroupFasting95 mg/dL105 mg/dL1 hour180 mg/dL190 mg/dL2 hour155 mg/dL165 mg/dL3 hour140 mg/dL145 mg/dLC/C criteria capture 54% more patients than NDDG criteria
30Outline Physiologic changes in pregnancy Diabetes in pregnancy Organ systems affectedMetabolic changes in pregnancyDiabetes in pregnancyClinical implicationsEpidemiology/TypesScreening and DiagnosisManagementFuture directionsNow that we have considered the general differences between glucose metabolism in the pregnant and non-pregnant state, let us move on to the discussion of when glucose metabolism goes awry – diabetes in pregnancy.
31Management: Glycemic control Significant benefit of insulin therapyPrior to insulin use, perinatal mortality was 65%After introduction of insulin therapy, perinatal mortality declined to 5%
32Management: Glycemic control Glycosylated Hemoglobin A1C (Hgb A1C) level should be less than or equal to 6%Levels between 5 and 6% are associated with fetal malformation rates comparable to those observed in normal pregnancies (2-3%)Goal of normal or near-normal glycosylated hemoglobin (Hgb A1C) level for at least 3 months prior to conceptionHgb A1C concentration near 10% is associated with fetal anomaly rate of 20-25%In the normal 120-day life span of the red blood cell, glucose molecules join hemoglobin, forming glycated hemoglobin. In individuals with poorly controlled diabetes, increases in the quantities of these glycated hemoglobins are noted.Once a hemoglobin molecule is glycated, it remains that way. A buildup of glycated hemoglobin within the red cell reflects the average level of glucose to which the cell has been exposed during its life cycle. Measuring glycated hemoglobin assesses the effectiveness of therapy by monitoring long-term serum glucose regulation. The HbA1c level is proportional to average blood glucose concentration over the previous four weeks to three months. Some researchers state that the major proportion of its value is related to a rather short term period of two to four weeks.
33Management: Overview Home self glucose monitoring Nutrition therapyHome self glucose monitoringMedical therapy if glycemic control not achieved with diet/exerciseSubcutaneous insulinOral hypoglycemic agents (Glyburide, Metformin)Antenatal monitoringMain goal is glycemic control, first by lifestyle adjustments (diet and exercise) and then by medication if necessary
34Management: Glycemic Control Blood glucose goals during pregnancyFasting < 95mg/dL1-hr postprandial < mg/dL2-hr postprandial am < 120mg/dL2 am < 120mg/dLNocturnal glucose level should not go below 60 mg/dLAbnormal postprandial glucose measurements are more predictive of adverse outcomes than preprandial measurements
35Management: Nutrition Caloric requirements:Normal body weight kcal/kg/dayDistributed 10-20% at breakfast, 20-30% at lunch, 30-40% at dinner, up to 30% for snacks (to avoid hypoglycemia)Caloric composition:40-50% from complex, high-fiber carbohydrates20% from protein30-40% from primarily unsaturated fats
36Management: Subcutaneous Insulin Therapy Insulin requirements increase rapidly, especially from 28 to 32 weeks of gestation1st trimester: U/kg/d2nd trimester: U/kg/d3rd trimester: U/kg/dRecall that the introduction of insulin therapy significantly reduced perinatal mortality
37Management: Subcutaneous Insulin Therapy Recall that the introduction of insulin therapy significantly reduced perinatal mortality“Regular” insulin = Humalog, Novalog
38Management: Oral Hypoglycemic Agents Glitazones (Avandia, Actos)Sensitize muscle and fat cells to accept insulin more readilyDecrease insulin resistanceSulfonylureasAugment insulin release1st generationConcentrated in the neonate hypoglycemia2nd generation (Glyburide)Low transplacental transferBiguanide (Metformin, aka Glucophage)Increases insulin sensitivityCrosses placentaRecall that the introduction of insulin therapy significantly reduced perinatal mortality
39Management Summary: Pregestational Diabetes Referral to perinatologist and/or endocrinologistMultidisciplinary approachRegular visits with nutritionistHgb A1C every trimesterFetal EchocardiogramLevel II ultrasoundOpthamologistBaseline kidney and liver function tests
40Management Summary: Pregestational Diabetes Optimize glycemic control – frequent insulin dose adjustmentsType 1: often have insulin pumpType 2: subcutaneous insulinFetal monitoring starting at weeks, depending on glycemic controlUltrasound to assess growth at 36 weeksDelivery at weeksPractice varies by institution, but the general principle of detecting fetal macrosomia and avoiding IUFD applies
41Management Summary: GDM Begin with diet / walk after each mealIf borderline/mild elevations, consider metformin (start at 500 mg daily)Counsel about increased PTD ratesUnlikely pre-existing DMIf elevations start out moderate to severe or metformin fails, proceed to subcutaneous insulin therapyNPH (long acting)Humalog/Novalog (short acting)
42Management Intrapartum Attention to labor pattern, as cephalopelvic disproportion may indicate fetal macrosomiaCareful consideration before performing operative vaginal deliveryHourly blood glucose monitoring during active labor, with insulin drip if necessaryNotify pediatrics if patient has poorly controlled blood sugars antepartum or intrapartum
43Management Postpartum For patients with pregestational diabetes, halve dose of insulin and continue to check blood glucose in immediate postpartum periodFor GDM patients who required insulin therapy (GDMA2), check fasting and postprandial blood sugars and treat with insulin as necessaryFor GDM patients who were diet controlled (GDMA1), no further monitoring nor therapy is necessary immediately postpartum
44Management Postpartum For all GDM patients, perform 75 gram 2-hour OGTT at 6 week postpartum visit to rule out pregestational diabetesMost common recommendation is for primary care physician to repeat2-hour OGTT every three years
45Diabetes in Pregnancy: Future directions ACOG recommendations on oral hypoglycemic agents will be updated as more safety and efficacy data become availableFurther development of programs for patient and provider educationExample: California Diabetes and Pregnancy Program (CDAPP) consultants develop, update and disseminate Sweet Success: Guidelines for Care which provides standards of practice for diabetes and pregnancy
46ReferencesACOG practice bulletin. Gestational Diabetes. Obstet Gynecol 2001;93:525-34ADA position statement. Standards of Medical Care in Diabetes. Diabetes Care 2006;29:S4-42Crowther CA et al. N Engl J Med 2005;352:Casey BM et al. Obstet Gynecol 1997;90:867-73Yang X et al. Diabetes Care 2002;9:UpToDate.comThanks to Dr. Bertha Chen and Dr. Aaron Caugheyfor sharing their slides