Diabetes in Pregnancy

Diabetes in Pregnancy Kirstin Woo, MD Palo Alto Foundation Medical Group May 5, 2009

Outline • Physiologic changes in pregnancy • Organ systems affected • Metabolic changes in pregnancy • Diabetes in pregnancy • Clinical implications • Epidemiology/Types • Screening and Diagnosis • Management • Future directions

Physiologic changes in pregnancy • Cardiovascular system • Respiratory system • Gastrointestinal system • Urinary system • Endocrine system • Genital Tract • Skin

Physiologic changes in pregnancy:Cardiovascular • Sodium and water retention • Reduced 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 15-20 beats/min)

Physiologic changes in pregnancy:Respiratory • Mechanical changes • Diaphragm rises 4 cm • Less negative intrathoracic pressure • No impairments in diaphragmatic or thoracic muscle motion • Lung compliance remains unaffected • Physiologic changes • Oxygen consumption increases 15-20 % • 50% of this increase is required by the uterus • Progesterone directly stimulates breathing • 70% of women experience dyspnea (increased desire to breathe)

Physiologic changes in pregnancy:Gastrointestinal • Mechanical • Pressure from growing uterus on stomach  reflux/heartburn • Pressure from growing uterus on lower portion of colon and rectum  constipation • Physiologic • Relaxation of sphincter muscle between esophagus and stomach • Progesterone (a smooth muscle relaxant) causes decreased GI motility and delayed gastric emptying

Normal glucose metabolism • Glucose enters bloodstream from food source • Insulin aids in storage of glucose as fuel for cells • Insulin resistance is defined as insensitivity of cells to insulin, therefore resulting in increased levels of insulin and glucose in the bloodstream

Metabolic changes in pregnancy • Caloric requirement for a pregnant woman is 300 kcal higher than the non-pregnant woman’s basal needs • Placental hormones affect glucose and lipid metabolism to ensure that fetus has ample supply of nutrients

Metabolic changes in pregnancy • Lipid metabolism: • Increased lipolysis (preferential use of fat for fuel, in order to preserve glucose and protein) • Glucose metabolism: • Decreased insulin sensitivity • Increased insulin resistance

Metabolic changes in pregnancy • Increased insulin resistance • Due to hormones secreted by the placenta that are “diabetogenic”: • Growth hormone • Human placental lactogen • Progesterone • Corticotropin releasing hormone • Transient maternal hyperglycemia occurs after meals because of increased insulin resistance

Metabolic changes in pregnancy Relative baseline hypoglycemia • Proliferation of pancreatic beta cells (insulin-secreting cells) leads to increased insulin secretion • Insulin levels are higher than in pregnant than nonpregnant women in fasting and postprandial states • Hypoglycemia between meals and at night because of continuous fetal draw • Blood glucose levels are 10-20% lower

Metabolic changes in pregnancy • Lipid metabolism • Increased serum triglyceride (300%) and cholesterol (50%) levels • Spares glucose for fetus, since lipids do not cross the placenta • Provides building blocks for increased steroid hormone synthesis

Diabetes in Pregnancy: Clinical Implications • Obstetric complications: • Increased incidence of miscarriage • Congenital malformations • Incidence 4X higher than in general population • Most significant remaining cause of fetal death is congenital malformation • Association with hypertensive disorders of pregnancy • Gestational hypertension • Preeclampsia

Diabetes in Pregnancy:Clinical implications Shoulder dystocia Fetal macrosomia

Diabetes in Pregnancy: Clinical Implications • Obstetric complications (cont’d.): • Preterm delivery • Intrauterine fetal demise • Traumatic delivery (e.g., shoulder dystocia) • Operative vaginal delivery • vacuum-assisted • forceps-assisted

Diabetes in Pregnancy: Clinical Implications • Fetal macrosomia • Disproportionate amount of adipose tissue concentrated around shoulders and chest • Respiratory distress syndrome • Neonatal metabolic abnormalities: • Hypoglycemia • Hyperbilirubinemia/jaundice • Organomegaly • Polycythemia • Perinatal mortality • Long term predisposition to childhood obesity and metabolic syndrome

Diabetes in Pregnancy: Epidemiology • Preexisting diabetes complicates ~1 % of pregnancies in US (>8 million women) • 154,000 (4%) of all pregnancies are affected by diabetes • 135,000 (88%) due to GDM • 12,000 (8%) due to Type 2 DM • 7,000 (4%) due to Type 1 DM

Diabetes 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

Diabetes in Pregnancy: Classification

Diabetes 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 levels • Type A2: abnormal OGTT compounded by abnormal glucose levels during fasting and/or after meals; additional therapy with insulin or other medications is required • Pregestational Diabetes Mellitus • Type 1: autoimmune process that destroys pancreatic b cells • Type 2 (“lifestyle diabetes”): acquired insulin resistance related to obesity

Pregestational Diabetes: Types 1 and 2

Gestational Diabetes (GDM) • Definition: Insulin resistance/ glucose intolerance first diagnosed during pregnancy • Prevalence: 1-14% of all pregnancies • Indicates predisposition to later development of Type 2 Diabetes • Chance of recurrence in future pregnancies: 30-84%

GDM: Risk factors • Maternal age >25 years • Body mass index >25 kg/m2 • Race/Ethnicity • Latina • Native American • South or East Asian, Pacific Island ancestry • Personal/Family history of DM • History of macrosomia

Gestational Diabetes (GDM)

GDM: Screening • Screening test • 50 gm 1-hour glucose challenge test (GCT) • Screening thresholds • 130mg/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)

GDM: Diagnosis • Fasting blood glucose>126mg/dL or random blood glucose >200mg/dL • 100 gm 3-hour glucose tolerance test (GTT) with 2 or more abnormal values

Management:Glycemic control • Significant benefit of insulin therapy • Prior to insulin use, perinatal mortality was 65% • After introduction of insulin therapy, perinatal mortality declined to 5%

Management: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 conception • Hgb A1C concentration near 10% is associated with fetal anomaly rate of 20-25%

Management:Overview • Nutrition therapy • Home self glucose monitoring • Medical therapy if glycemic control not achieved with diet/exercise • Subcutaneous insulin • Oral hypoglycemic agents (Glyburide, Metformin) • Antenatal monitoring

Management: Glycemic Control • Blood glucose goals during pregnancy • Fasting < 95mg/dL • 1-hr postprandial < 130-140mg/dL • 2-hr postprandial am < 120mg/dL • 2 am < 120mg/dL • Nocturnal glucose level should not go below 60 mg/dL • Abnormal postprandial glucose measurements are more predictive of adverse outcomes than preprandial measurements

Management:Nutrition • Caloric requirements: • Normal body weight - 30-35 kcal/kg/day • Distributed 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 carbohydrates • 20% from protein • 30-40% from primarily unsaturated fats

Management:Subcutaneous Insulin Therapy • Insulin requirements increase rapidly, especially from 28 to 32 weeks of gestation • 1st trimester: 0.7-0.8 U/kg/d • 2nd trimester: 0.8-1 U/kg/d • 3rd trimester: 0.9-1.2 U/kg/d

Management:Subcutaneous Insulin Therapy “Regular” insulin = Humalog, Novalog

Management:Oral Hypoglycemic Agents • Glitazones (Avandia, Actos) • Sensitize muscle and fat cells to accept insulin more readily • Decrease insulin resistance • Sulfonylureas • Augment insulin release • 1st generation • Concentrated in the neonate  hypoglycemia • 2nd generation (Glyburide) • Low transplacental transfer • Biguanide (Metformin, aka Glucophage) • Increases insulin sensitivity • Crosses placenta

Management Summary:Pregestational Diabetes • Referral to perinatologist and/or endocrinologist • Multidisciplinary approach • Regular visits with nutritionist • Hgb A1C every trimester • Fetal Echocardiogram • Level II ultrasound • Opthamologist • Baseline kidney and liver function tests

Management Summary:Pregestational Diabetes • Optimize glycemic control – frequent insulin dose adjustments • Type 1: often have insulin pump • Type 2: subcutaneous insulin • Fetal monitoring starting at 28-32 weeks, depending on glycemic control • Ultrasound to assess growth at 36 weeks • Delivery at 38-39 weeks

Management Summary:GDM • Begin with diet / walk after each meal • If borderline/mild elevations, consider metformin (start at 500 mg daily) • Counsel about increased PTD rates • Unlikely pre-existing DM • If elevations start out moderate to severe or metformin fails, proceed to subcutaneous insulin therapy • NPH (long acting) • Humalog/Novalog (short acting)

Management Intrapartum • Attention to labor pattern, as cephalopelvic disproportion may indicate fetal macrosomia • Careful consideration before performing operative vaginal delivery • Hourly blood glucose monitoring during active labor, with insulin drip if necessary • Notify pediatrics if patient has poorly controlled blood sugars antepartum or intrapartum

Management Postpartum • For patients with pregestational diabetes, halve dose of insulin and continue to check blood glucose in immediate postpartum period • For GDM patients who required insulin therapy (GDMA2), check fasting and postprandial blood sugars and treat with insulin as necessary • For GDM patients who were diet controlled (GDMA1), no further monitoring nor therapy is necessary immediately postpartum

Management Postpartum • For all GDM patients, perform 75 gram 2-hour OGTT at 6 week postpartum visit to rule out pregestational diabetes • Most common recommendation is for primary care physician to repeat 2-hour OGTT every three years

Diabetes in Pregnancy:Future directions • ACOG recommendations on oral hypoglycemic agents will be updated as more safety and efficacy data become available • Further development of programs for patient and provider education • Example: 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

References • ACOG practice bulletin. Gestational Diabetes. Obstet Gynecol 2001;93:525-34 • ADA position statement. Standards of Medical Care in Diabetes. Diabetes Care 2006;29:S4-42 • Crowther CA et al. N Engl J Med 2005;352:2477-86 • Casey BM et al. Obstet Gynecol 1997;90:867-73 • Yang X et al. Diabetes Care 2002;9:1619-24 • UpToDate.com Thanks to Dr. Bertha Chen and Dr. Aaron Caughey for sharing their slides

Diabetes in Pregnancy