J. David Spencer, D.O., F.A.C.O.O.G. Diabetes : a group of diseases due to high levels of blood glucose Defects in insulin production and / or the action of insulin Affects 25.8 million people, 8.3 % of the population of the United States 18.8 million people diagnosed with Diabetes 7 million people undiagnosed 1.9 million people over age 20 dxed in 2010 12.6 million, or 10.8 % of U.S. women over age 20 have diabetes Higher than normal blood glucose or glycosylated Hemoglobin A1C levels, but not high enough to be classified as diabetes. American Diabetes Association values placing person at risk for DM: Fasting blood sugar: 100 – 125 mg/dl. 2 hours after 75 gram glucose load:140-190 Hemoglobin A1C value: 5.7 – 6.4 % (or <6%) Developing type 2 diabetes Heart disease Stroke Gestational diabetes Pregestational or Overt Diabetes : a woman diagnosed with diabetes prior to becoming pregnant Gestational Diabetes : a woman with glucose intolerance first diagnosed while pregnant Casual (random) blood glucose value over 200 mg/dl, with classic symptoms: polydipsia, polyuria, unexplained weight loss, ketoacidosis OR Fasting (no caloric intake for 8 to 14 hours) plasma glucose over 125 mg/dl OR After 75 gram glucose load, 2 hour plasma glucose over 200 mg/dl Type 1 : formerly insulin dependent, or juvenile onset diabetes Type 2 : Formerly non-insulin dependent, or adult onset diabetes Other types of DM : genetic, drug related, chemical diabetes Gestational diabetes Type 1 diabetic women : approx. 2 % of pregnancies that have diabetes Type 2 diabetic women : approx. 8 % of pregnancies with diabetic mother Gestational Diabetes Mellitus : Women who develop diabetes in pregnancy account for about 90 % of pregnancies with diabetes Incidence of DM in the U.S. is increasing Incidence of Obesity in the U. S. is an epidemic Strong relationship of obese patients developing diabetes. This correlation has been called Diabesity In 2008, about 60 % of reproductive age women in the U. S. were overweight or obese (What percent now?) Diabetic women planning to become pregnant should optimize their health prior to conception with: Nutritional management Weight management Glycemic control BUT about 50% of all pregnancies are unplanned, therefore unprepared Euglycemia at the time of conception reduces the risks of : spontaneous abortion : congenital anomalies Very strong positive correlation between hyperglycemia during embryonic organogenesis and congenital (not chromosomal) anomalies Birth defects affect about 1 in 33 pregnancies and are a leading cause of pregnancy loss and neonatal deaths in the U. S. Not totally understood is how hyperglycemia causes congenital anomalies Diabetic women with good glycemic control have no increase incidence of birth defects compared to general population Unrecognized / undiagnosed or poorly controlled diabetes increases maternal as well as fetal risks in pregnancy Many reproductive age women are in this category, and coupled with unplanned pregnancies, many women and their babies are at risk Goals - achieve and maintain excellent control of diabetes without hypoglycemia - evaluate any other medical conditions that may complicate a pregnancy Glycosylated Hemoglobin A1C measurements reflect blood sugar levels of preceeding 8 to 12 weeks can be useful in assessing blood sugar control before becoming pregnant Obesity – even if not (yet) diabetic, overweight and obese women have more complications in pregnancy, and a higher than usual rate of Gestational Diabetes Mellitus. Weight loss will decrease some of the complications of pregnancy in obese women Most weight loss medications should not be used in pregnancy – so stop before conceiving Diabetics may have hyperlipidemia, and Statin drugs are Category X and should not be used especially early in gestation Dietary changes may help some, if statins have been used In women who have had diabetes for over 10 years, over 30 % have hypertension. Some commonly used anti-hypertensive medications are not teratogenic, and may be continued in pregnancy - Methyldopa - Calcium channel blockers - Beta blockers Diuretics : may affect fetal renal development, amniotic fluid levels Angiotensin Converting Enzyme inhibitors and Angiotensin Receptor Blockers -probably safe in first trimester, but later in pregnancy reduce fetal renal blood flow, decrease fetal urine output and result in oligohydramnios If nutritional management and exercise do not result in normal blood sugar levels, medication is indicated. Insulin Oral hypoglycemic agents Insulin most like human insulin is preferred for use in pregnancy - fewer antibodies limited transplacental crossing - no teratogenicity Most clinical experience with Lispro (Humulin) Aspart (Novolog), Regular and NPH insulin Type 1 diabetics should remain on insulin in pregnancy - First generation sulfonylureas should not be used in pregnancy – placental transfer results in fetal hyperinsulinemia, prolonged newborn post-partum hypoglycemia Glyburide, second generation – low placental transfer. Stimulates maternal pancreas to produce more insulin May be continued in pregnancy Metformin – frequently used in women with insulin resistance, metabolic syndrome, infertility, polycystic ovary syndrome Does cross placenta, no teratogenicity, minimal fetal affects. Decreases maternal peripheral resistance to insulin, inhibits gluconeogenesis May be continued in pregnancy The control of blood sugar levels, and evaluation of medical conditions and pre-pregnancy medications, will allow the woman to have a healthier and safer start to her pregnancy Occur to assure adequate supply of metabolic fuels to the growing fetus and accommodate energy needs of the mother Some of these changes can be affected by pre-gestational diabetes. Glucose homeostasis is a balance of insulin secretion and insulin resistance Both effects occur at increased rates in pregnancy Insulin receptor sites are decreased by Human Chorionic Somatomammotropin, Prolactin, and Placental Human Growth Hormone. Endogenous glucose production is increased Pregnancy hormones cause hyperplasia of pancreatic islet beta cells, increasing insulin After eating, increases in insulin release cause increases in glucose uptake in muscle, fat In fasting state in pregnancy, increased insulin levels magnify the hypoglycemic state, but gluconeogenesis and transfer of glucose through placenta maintain fetal glucose levels In the third trimester of pregnancy : o Fetal growth accelerates o Maternal and fetal metabolic demands increase o Insulin resistance increases Pregestational, or gestational impairments of glucose metabolism adversely affect control of blood sugar levels, resulting in hyperglycemia Gestational diabetes mellitus is impaired glucose tolerance with onset or first recognition during pregnancy 5 to 10 % of U. S. pregnancies are complicated by diabetes Women with Type 1 diabetes - about 1-2 % Women with Type 2 diabetes - about 10 % Women developing DM in pregnancy – 90% Because of serious complications of unrecognized diabetes in pregnancy, screening for GDM has been done for many decades Initial screening looks at maternal factors Blood tests make the diagnosis Low risk (the woman must meet all criteria) o Age less than 25 o Weight normal before pregnancy (BMI 19-25) o No history of abnormal glucose tolerance o No history of adverse pregnancy outcome o No known first degree relatives with diabetes o Ethnicity with low prevalence of diabetes High risk o Over age 25 (some use 30) o Obese (BMI over 30 kg/m2, or weigh over 90 kg) o Polycystic ovary syndrome o History of gestational diabetes o Previous Macrosomic / Large for Gestational age infant o Previous unexplained pregnancy loss High risk -Strong immediate family history of diabetes -Previous child with congenital anomaly -Elevated blood sugar (FBS >140; RBS >200) -“Prediabetes” – mildly elevated glucose or Glycosylated Hemoglobin A1C -Member of ethnic group with increased incidence of diabetes Low risk patients – oral glucose load 24 to 28 weeks gestation High risk patients – screen with blood test as soon as possible in the pregnancy. One step – first option 2 hour glucose tolerance test 75 gram oral glucose load, draw blood sugar 2 hours later some modify and do Fasting : <95 mg/dl 1 hour : <180 mg/dl 2 hour : <155 mg/dl One step – second option 3 hour glucose tolerance test Fasting (for 8 – 14 hours) : <95 mg/dl 100 gram oral load of glucose 1 hour post-prandial : <180 mg/dl 2 hour post-prandial : <155 mg/dl 3 hour post-prandial : < 140 mg/dl A diagnosis of GDM is made with 2 abnormal values Two step option First done is 50 gram oral glucose load, without regard to time of day or last meal blood sugar one hour later : <140 (or <130) If elevated, the previously described 3 hour glucose tolerance test, with 100 gram load, same values, is performed Abnormal glucose screening tests, or elevated glycosylated hemoglobin A1C prior to 20 weeks gestation is strongly suspicious for unrecognized, undiagnosed pregestational DM Uncommonly, type 1 DM may be discovered as presenting with ketoacidosis in pregnancy, especially if in first trimester Both, by definition, are still GDM Gestational diabetes dxed early in pregnancy with high risk patient may very well be pregestational diabetes Possible DM related underlying medical conditions need to be investigated, such as diabetic vasculopathy Proposed in the 1970’s, as a reflection of duration and multi-organ medical impact of women with diabetes who became pregnant TYPE AGE AT ONSET (YRS) DURATION OF DM (YRS) COMPLICATIONS A1 ANY AGE ANY LENGTH None; diet controlled A2 ANY AGE ANY LENGTH None; requires RX B <20 OR <10 No vascular disease C 10-19 OR 10-19 No vascular disease D1-5 <10 OR >20 Retinopathy or HTN E(NOW CLASS D3) Arterial calcification F Proteinuria; nephropathy G Pregnancy failures H Arterisclerotic heart disease R Proliferative retinopathy T After renal transplant Glycosylated Hemoglobin A1C – in pregnancy mean red blood cell production increases, RBC life is shortened Gly Hgb A1C in pregnancy is a reflection of mean RBC blood glucose levels over 4 to 6 weeks, not 8 – 12 weeks More frequent monitoring of this test will give better reflection of long term glycemic state Caloric demands are increased in pregnancy Carbohydrate type and amount should be decreased in diabetics in pregnancy Weight gain recommendation in pregnancy has changed PRE-PREGNANCY BMI BMI (KG/M2 ) TOTAL WT GAIN RATE OF WT (LBS) GAIN 2nd-3rd TRIMESTERS (PER WK) UNDERWEIGHT <18.5 28-40 1-1.3 NORMAL WT 18.5-24.9 25-35 0.8-1 OVERWEIGHT 25-29.9 15-25 0.5-0.7 OBESE >30 11-20 0.4-0.6 Weight gain beyond IOM guidelines in pregnancy is associated with increased adverse maternal and neonatal outcomes Home glucose monitoring determines if diet or medication maintains tight glycemic control Fasting blood sugar value should be < 95 mg/dl 1 hour postprandial value should be <140 2 hour postprandial value should be <120 Peak postprandial glucose concentration is 60 to 90 minutes after eating Hyperglycemia and Adverse Pregnancy Outcomes study (HAPO) – even small elevations in blood glucose levels in pregnancy are associated with increased maternal and fetal complications in pregnancy Type 1 diabetics are maintained on insulin, although type and dose will change in pregnancy Type 2 and GDM mothers may try oral hypoglycemic drugs, but may need insulin to give appropriate control Nutritional management is maintained Frequent home glucose monitoring is required to avoid prolonged hyperglycemic or hypoglycemia in the pregnant diabetic patient Perinatal mortality decreased due to improved diabetic metabolic control, fetal surveillance, and neonatal care - 1960’s > 20 % - now < 5% Risk and severity of complications are related to severity and duration of hyperglycemia Poorly controlled gestational diabetics may have serious complications Women with pregestational diabetes are at increased risk if poorly controlled prior to and during pregnancy Retinopathy – esp in pregestational DM Neuropathy Nephropathy - proteinuria Cardiovascular – HTN, PIH, preeclampsia Diabetic ketoacidosis Infections Spontaneous abortion Congenital anomalies o Cardiovascular o Musculoskeletal - Central Nervous System - Genitourinary Fetal Growth Restriction Macrosomia – birth injuries Abnormalities of amniotic fluid Unexplained fetal demise First Trimester - viability, gestational age Second Trimester - fetal structure (ultrasound) - biochemical markers Third Trimester - fetal well being: NST,CST,BPP - ? Estimated fetal weight? Polycythemia - Hyperviscosity Neonatal hypoglycemia Neonatal hypocalcemia Neonatal hyperbilirubinemia Respiratory distress syndrome Neurologic or Developmental issues Long term risks (obesity, diabetes) Whatever the type of diabetes 1 to 3 days after delivery, fasting or random glucose – monitor levels and RX Gestational diabetes 6 to 12 weeks after delivery, 75 gram oral glucose load Over 50% of GDM patients develop type 2 DM 30 to 50 % recurrence of GDM in other pregnancy Women with diabetes can have safe, successful pregnancies with proper care prior to and during the pregnancy. Thank you. ? Questions ? 1. Centers for Disease Control and Prevention. National diabetes fact sheet; national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA U.S. Department of Health and Human Services, centers for Disease Control and Prevention 2011. 2. Landon MB, Gable SG. Gestational diabetes mellitus Obstet Gynecol 2011; 118(6): 1379-1393 3. Correa A, Gilboa SM, Botto LD, et al. Lack of periconceptional vitamins or supplements that contain folic acid and diabetes mellitus associated birth defects. Am J Obstet Gynecol March 2012; 218: 218-221 4. Dhulkotia JS, Ola B, Fraser R, et al. Oral hypoglycemic agents vs. insulin in management of gestational diabetes: a systematic review and metaanalysis. Am J Obstet Gynecol Nov 2010; 203: 457-465 5. Sulak JS. Know the normal numbers – and yours! The Female Patient 2012; 37: 1720. 6. International Association of Diabetes and Pregnancy Study Group Consensus Panel. Metzger BE, Gabbe SG, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010; 33 (3): 676-682. 7. HAPO Study Cooperative Research Group. Metzger BE, Lowe LP, et al. Hyperglycemia and Adverse Pregnancy Outcomes. N Engl J Med 2008; 358: 1991. 8. U. S. Preventive Services Task Force. Screening for gestational diabetes mellitus: U. S. Preventive Services Task Force recommendation statement. Ann Intern Med 2008; 148: 759. 9. Correa A, Gilboa SA, Besser LM, et al. Diabetes mellitus and birth defects. Am J Obstet Gynecol 2008; 199: 237. 10. Yee LM, Cheng YW, Inturrisi M, et al. Effect of gestational weight gain on perinatal outcomes in women with type 2 diabetes mellitus using the 2009 Institute of Medicine guidelines. Am J Obstet Gynecol Sep. 2011; 205: 257. 11. Moore, LE. Gestational diabetes: Should you use oral agents? Contemp Ob Gyn Feb 2012 12. Metzger BE, Buchanan TA, Coustan DR, et al. Summary and recommendations of the Fifth International Workshop-Conference on Gestational Diabetes. Diabetes Care 30 (Suppl 2): S251, 2007. 13. Preconceptional counseling (Chapter 7); Diabetes (Chapter 52). In Cunningham FG, Leveno KJ, et al (eds). Williams Obstetrics, 23rd ed. Saunders Elsevier, New York, 2010. 14. Endocrinology of Pregnancy (Chapter 8); Maternal Nutrition (Chapter 10); Diabetes in Pregnancy (Chapter 46). In Creasy RK, Resnick R, Iams J. (eds). Creasy and Resnick’s Maternal-Fetal Medicine: Principles and Practice, 6th ed. New York, McGraw Hill Medical, 2009. 15. Jovanovic L. Glycemic control in women with type 1 and type 2 diabetes mellitus during pregnancy. Up To Date, Feb 2012. 16. D’Antona D. Maternal endocrine and metabolic adaptation to pregnancy. Up To Date, Oct 2010.