Diabetes in Pregnancy Mark Alanis, MD, MSCR Assistant Clinical - PDF document

2/4/2016 Diabetes in Pregnancy Mark Alanis, MD, MSCR Assistant Clinical Professor Maternal-Fetal Medicine University of Colorado Health Memorial Hospital, Colorado Springs, CO disclosures I have no relevant financial conflicts of interest with any commercial entity to disclose. I will discuss the off-label use of insulin and insulin pumps for use in pregnancy. I will not discuss the off label use of any other pharmaceutical agent or medical device during this lecture. 1

2/4/2016 objectives At the end of this lecture, you will be better prepared to: Counsel patients on the risks of gestationald and pregestational diabetes Sort through the confusion about gestational diabetes testing paradigms Reduce diabetes-related adverse outcomes through achieving maternal euglycemia Frederick Banting Born 1891, died 1941 Canadian physician scientist Discovery of insulin, 1922 Nobel prize, 1923 2

2/4/2016 Pricilla White Born 1900, died 1989 Mentored by Elliot P. Joslin Among first to show importance of strict glucose control in pregnancy White’s Classification in 1949 Banting Medal recipient White’s Classification Description Class Fetal Growth Gestational Diabetes, no insulin A1 No vascular disease High Risk for Macrosomia Gestational Diabetes, insulin A2 Age of onset, ≥ 20 y B1 Duration < 10 y, no vascular lesions B2 Age of onset, 10-19 y C1 Duration 10-19 y, no vascular lesions C2 Age of onset, < 10 y D1 Duration, ≥ 20 y D2 Benign (non-proliferative) retinopathy D3 Vascular disease High Risk for IUGR Calcified arteries of the legs D4 Calcified arteries of the pelvis E Nephropathy F Many failures G Cardiac disease H Proliferating retinopathy R Renal transplant T Pridjian G. Obstet Gynecol Clin N Am 2010;37:143, adapted from : White P. Am J Obstet Gynecol 1978;130:228 3

2/4/2016 ADA Classification Diabetes Type Findings Phenotype Type 1 Autoimmune destruction of β -cells; Onset in childhood or 33% concordance among mono- adolescence; Thin; zygotic twins; Absolute insulinopenia Ketoacidosis Type 2 Progressive insulin secretory defect; Adult-onset, obese, insulin resistance; 58-100% metabolic syndrome, concordance among mono-zygotic hyperosmolar coma twins Gestational Same as type 2 diabetes Onset during pregnancy, resolves in postpartum; Rare, other Pancreatic damage or insufficiency, Cystic fibrosis genetic defects in insulin action American Diabetes Association, Standards of Medical Care in Diabetes – 2013. Diabetes Care 2013;36, Suppl 1: S11 Epidemiology 15% Gestational DM Pregestational DM 85% Albrecht SS, et al. Diabetes Care 2010;33:768 4

2/4/2016 Prevalence increasing rapidly Hospital Discharge Data 1994-2004 of 43+ million delivery discharges Percent of Deliveries (%) Type N 1994 1999 2004 % change All diabetes 1,863,746 3.49 4.04 5.47 56.3 GDM 1,578,703 2.95 3.42 4.61 56.2 Type 1 130,300 0.24 0.31 0.33 33.2 Type 2 87,477 0.09 0.16 0.42 366.7 Albrecht SS, et al. Diabetes Care 2010;33:768 U.S. Adults Aged 18 Years or older OBESITY 1994 2000 2010 No Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% >26.0% DIABETES 1994 2000 2010 No Data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% >9.0% CDC’s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics 5

2/4/2016 New diagnoses 2002-2005 Youths 10-19 years of age 40 Rate (per 100,000 per year) Type 2 Type 1 0 CDC, 2011 National Diabetes Fact Sheet, data from SEARCH for Diabetes in Youth Study: Type 1 Diabetes Acute onset Childhood or adolescence Islet cell autoimmune antibodies β -cell destruction Absolute insulinopenia Lifelong requirement for insulin Threat of diabetic ketoacidosis High rate of vascular disease High rate of pregnancy complications 6

2/4/2016 Type 2 Diabetes Insidious onset Asymptomatic Relative insulin deficiency Decreased insulin sensitivity in skeletal muscle Decreased insulin response on hepatic glucose production Inadequate β -cell response for given glucose level Typically older, overweight or obese, family history Most pregnant patients are White’s Class B High rate of pregnancy complications Gestational Diabetes Onset in late second trimester Asymptomatic Relative insulin deficiency Decreased insulin sensitivity in skeletal muscle Decreased insulin response on hepatic glucose production Inadequate β -cell response for given glucose level Typically older, overweight or obese, family history Lower rate of pregnancy complications 7

2/4/2016 Counseling the pregestational diabetic patient lots of risks … how do you communicate it all? ARS Which diabetic patient has the highest risk for pregnancy complications? a) Type 1 diabetes b) Type 2 diabetes c) Gestational diabetes d) No difference between the 3 types 8

2/4/2016 ARS Pregnancy affects retinopathy in what way? a) It occurs de novo due to pregnancy b) If already present at conception, it worsens during pregnancy, then returns to baseline c) If already present at conception, it worsens during pregnancy, permanently d) It is not affected by pregnancy ARS The most common cause of perinatal mortality in diabetic pregnancies is: a) Stillbirth b) Congenital anomaly c) Respiratory distress d) Preterm birth 9

2/4/2016 ARS What is the incidence of brachial plexus injury with shoulder dystocia? a) 5% b) 15% c) 25% d) 35% ARS Which is true in normal pregnancy? a) Fasting glucose increases over gestation b) Insulin sensitivity increases in first trimester c) Postprandial glucose increases over gestation d) All of the above 10

2/4/2016 Diagnosing Diabetes Type 1 Gestational  Pregestation Two-Step versus One Step  Autoantibodies  Overly confusing set of  Clinical characteristics parameters  1-2% of persistent DM  Philosophical argument of after diagnosis of GDM individual versus public health benefit Type 2  Pregestation  Clinical characteristics  98% of persistent DM after diagnosis of GDM GDM Screening Dilemmas Two Step When should Should you you do it? fast? 1-hour 50 g What cutoff High false negative glucose load to use? and positive rates What cutoffs 3-hour 100 g Very to use? glucose load inconvenient Risk versus harm GDM Arbitrary with diagnosis Yes or No diagnosis 11

2/4/2016 GDM Screening Dilemmas One Step 3-fold increase in 2-hour 75 g Moderately prevalence glucose load inconvenient GDM Arbitrary Yes or No diagnosis Timeline of Recent GDM Diagnostic Crisis 1979 - 2009 2008 2010 2011 2012 2013 2014 12

2/4/2016 HAPO Hyperglycemia and Adverse Pregnancy Outcomes HAPO Study Group N Engl J Med 2008;358:1991 HAPO and IADPSG International Association of Diabetes in Pregnancy Study Group Study Features IADPSG had two goals:  >25,000 patients 1. Use HAPO to develop cutoffs discretely linked  International, multicenter to GDM-related  2-hour, 75 g glucola morbidities  Providers blinded to test 2. Develop international results standard diagnostic  Intent was to redefine guidelines GDM diagnostic testing cutoffs based on Cutoffs later arbitrarily outcomes ...but this defined based Odds Ratios wasn’t the case of 1.75 for morbidities HAPO Study Group N Engl J Med 2008;358:1991 IADPSG Diabetes Care 2010;33:676 13

2/4/2016 More GDM Diagnostic Dilemmas Should you try to differeniate type 1 from It’s not type 2 diabetes in unclear situations? important What do you call a patient whom you ADA/IADPSG: overt diabetes diagnose early in pregnancy: ACOG: pregestational or gestational ? undiagnosed type 2 DM Should the hemoglobin A1c be used to It can, but it diagnose diabetes mellitus in pregnancy? shouldn’t be the only test you order EVEN More Diagnostic Dilemmas Should early screening be performed? Yes! (ADA and ACOG) Should you use NDDG or Carpenter- ACOG: either Coustan criteria for the diagnosis in Two- Step screening? Should the One-Step paradigm be used No! (ACOG and NIH) for the diagnosis of GDM? Yes! (ADA, IADSPG, WHO) 14

2/4/2016 GDM Screening Test Features A 1-hour, 50 g glucose cutoff of 140 mg has 15% false negative rate (CC criteria) USPSTF Systematic Review Ann Intern Med 2013;159:115 2-Step versus 1-Step Criteria Year Fasting 1-hour 2-hour 3-hour mg/dL mg/dl mg/dL mg/dL C-C 1982 95 180 155 140 (100 g load) Two-Step NDDG 1979 105 190 165 145 CDA 2008 95 191 160 WHO 1985 126 140 One-Step (75 g load) IADPSG 2010 92 180 153 NIH Consensus Development Conference Statement Vol. 29, Number 1. March 4-6, 2013 15

2/4/2016 GDM Screening and ACOG 2013 Practice Bulletin No. 137  Still allows for no lab screening for low-risk patients  Use either 135 mg/dL or 140 mg/dL for 1-hour cutoff  Use either Carpenter-Coustan or National Diabetes Data Group for 3-hour cutoffs  Screen at-risk patients early in pregnancy  GDM in previous pregnancy  Known impaired glucose metabolism  Obesity  Does NOT say WHEN or HOW to perform early screening Complications Maternal and Obstetric Fetal and Neonatal  Kidney dysfunction  Miscarriage and stillbirth  Retinopathy  Structural malformations  Myocardial infarction  Fetal overgrowth  Preeclampsia  Fetal growth restriction  Cesarean section  Birth injury  Preterm birth  Prematurity  Hypoglycemia  Infant death 16