Disclosures I have nothing to disclose 1 4/12/2018 Objectives - PDF document

4/12/2018 Diabetes in Pregnancy Ingrid Block-Kurbisch, MD, Associate Clinical Professor of Medicine Associate Physician, OB/GYN, UCSF April 12, 2018 Disclosures I have nothing to disclose 1

4/12/2018 Objectives Definitions: GDM, Pre-GDM 1 & 2 Epidemiology Implications of GDM and PEDM on outcomes Pre-conception Care Populations at high risks for adverse outcomes Screening for GDM Treatment and questions about oral agents Monitoring Delivery planning Post-conception Care Definitions Hyperglycemia first detected in pregnancy: - Gestational DM (GDM) - Diabetes in pregnancy (DIP) Pre-gestational DM (PEDM): - Type 1 - Type 2 - Other (Monogenic DM, CF, other) GDM - A1GDM: diet controlled - A2GDM: medication + Diet controlled 2

4/12/2018 Diabetes in Pregnancy High Risk Populations Race/Ethnicity: Most common complication of - Hispanic, NA, AA, Asian or pregnancy in the US Pacific Islander FH of DM2, GDM 7% of all pregnancies BMI> 25 or > 23 in Asian Americans Prevalence of GDM HTN,CVD, Dyslipidemia correlates well with DM2 Pre-diabetes PCO-S Global prevalence of Acanthosis Nigricans total hyperglycemia in Prior GDM pregnancy 16.9% Hx of large infant (> 4000 gm) Sedentary life style Age Related Prevalence Rates of PEDM and GDM in the US 1993 – 2009 a Preexisting DM (PDM), b Gestational DM ( GDM ) Correa, A., Bardenheimer, B., Elixhauser, A et al. Maternal Child Health J. (2015) 19:635 3

4/12/2018 Proportion of Diabetes Types in Pregnancy in the US DM2 DM1 0.3- 8 + % GDM 0.8% 86% Monogenic DM • Hyperthyroidism • Other Glucocorticoids • Cystic Fibrosis • Terbutaline • Pheochromocytoma • Acromegaly • Contributing Factors to Insulin Resistance in Pregnancy Human placental Lactogen (HPL) Prolactin,Cortisol (Human Chorionic Somatomammotropin) Insulin Resistance Free Fatty Acids, Leptin,TNF-a Resistin, Adiponectin 4

4/12/2018 Physiologic Rise in Insulin Levels during Pregnancy Onset of classic GDM Insulin Level and Increased Sensitivity Resistance 250% increase 0 6 9 12 16 18 24 28 34 36 40 Weeks of Gestation Delivery Maternal Implications of GDM Gestational HTN Preeclampsia/ Eclampsia Pre-term delivery Operative delivery Emotional distress over outcome Weight retention post-partum Up to 50% future risk for DM2 5

4/12/2018 Fetal Implications of GDM Fetal/Neonatal/Child and Adult: LGA / Macrosomia Stillbirth Shoulder dystocia Neonatal hypoglycemia ( NICU stay ) Childhood obesity DM2 GDM in female offspring Implications of PEDM Maternal Risks Severe hypoglycemia (especially first trimester) Progression of advanced chronic complications - Proliferative retinopathy - Proteinuria/CKD - Gastroparesis Pregnancy induced HTN Cardiovascular event if longstanding DM and AMA Preeclampsia and Eclampsia Operative delivery Anxiety and emotional distress over fetal outcomes AMA: Advanced maternal age 6

4/12/2018 Implications of PEDM Fetal Risks Congenital Anomalies due to - Hyperglycemia - Teratogenic drugs - Lack of folic acid supplementation SAB and Stillbirth Macrosomia Shoulder Dystocia Delayed Lung Maturation Perinatal metabolic Abnormalities: - Hyperbilirubinemia - Hypoglycemia Increased risk of childhood obesity and DM 2 Postnatal and future Risks due to GDM and PMD Macrosomic Neonate • Hypoglycemia • Hyperbilirubinemia • Polycythemia • Respiratory Distress • Cardiomyopathy • Brachial Plexus injuries Long-term Sequelae • Congenital anomalies (if early GDM) • Delayed cognitive and motor development • Increased risk for type 2 DM • Childhood Obesity 7

4/12/2018 Congenital Anomalies in Infants of Diabetic Mothers with PDM Gestational Age of Occurrence Fetal Anomaly (weeks after LMP) Caudal regression 5 Anencephaly 6 Spina bifida 6 Cardiac anomalies 7-8 Anal/Rectal atresia 8 Renal anomalies 7 Situs inversus 6 Mary Martin et al; Basic and Clinical Endocrinology, 1994 Preconception Counseling Awareness Counseling (at every visit) - Planning and preventing pregnancy - importance of tight metabolic control - diabetes/pregnancy risks of complications - family planning advise Overview of preconception care - for women contemplating pregnancy In-depth assessment and personalized recommendations - for women actively planning a pregnancy Glycemic Goals: ADA: HbA1c < 6.5%, FPG < 95 mg, 1-hr postprandial < 140 ACOG:HbA1c< 6.0%, FPG < 95 mg, 1-hr postprandial < 140 8

4/12/2018 Goals of Preconception Care Planned pregnancy Lowest A1C without excessive hypoglycemia Effective contraception until stable control Evaluate for existing DM complications Discontinue contraindicated drugs Start pre-natal Vitamin Optimize Pre-pregnancy weight Include women with Pre-DM Observed Common Characteristics of Planned versus Unplanned Pregnancy Planned Pregnancy Unplanned Pregnancy Positive relationship with Negative relationship with health care team healthcare team Positive pre-conception Discouraged from advise pregnancy More often Type 1 DM More often Type 2 DM European or white Ethnic Minority Group Higher socio-economic Lower socio-economic status status Higher level of education Lower level of education Married or stable Unmarried/unsupportive relationship partner Employed Unemployed Older Younger Non-smoker Smoker R. Temple; Preconception care for women with DM; Clin. Obstetrics and Gynecology; October 25, 2010 9

4/12/2018 Observations and Concerns in Women with Type 2 DM Fewer planned pregnancies Pre-conception counseling in only 25 % Contraception discussion in only 32% Discussion about obstetric and fetal risk is rare Folic Acid not prescribed prior to conception Late entry into pre-natal care Diagnosis of DM 2 often made in pregnancy Higher rate of fetal anomalies/perinatal mortality Higher rate of maternal complications Teratogenic medications continued post-conception R. Temple; Preconception care for women with DM; Clin. Obstetrics and Gynecology; October 25, 2010 Congenital Malformations in Women with or without PCC Wahabi et al, BMC Public Health 2012 PCC = Pre-conception care 10

4/12/2018 Who to Refer to High Risk OB for Preconception counseling Longstanding PEDM Established micro vascular complications Chronic HTN Hypoglycemia unawareness or DKA Uncontrolled hyperglycemia Advanced maternal age ( > 35 yrs) Prior history of preeclampsia or pregnancy complications History of moderate to severe obesity Preconception Care and Planning PMD Endocrinologist CDE Obstetrician RD Ophthalmologist DM Self care Nephrologist Pregnancy Cardiologist planning Education Support at Support at Home work 11

4/12/2018 Medication Safety in Pregnancy and Postpartum Medication Cat Pregnancy (ACOG) Lactation Aspart B Preferred (FDA approved) Safe, not absorbed Lispro B Preferred through GI tract, Glulisine C Second tier but likely safe Regular B Not first choice Regular U-500 X Not studied in pregnancy Not safe, high risk of error and severe lows NPH B First choice Basal Insulin in GDM Glargine C Safe Glargine U-300 X Not studied in pregnancy Risk of severe lows Detimir B Safe and FDA approved Degludec C Not studied in pregnancy Antihyperglycemic: Glyburide B/C Not used in Type 2 DM, crosses placenta Risk unclear Glipizide C Not studied Safety unknown Metformin B Crosses placenta, safe? Second line No long-term data Incretins B Not recommended No safety data SGLT- 2i’s C Not recommended No safety data Antihypertensive: ACE-I, ARB, Thiazide C/D Discontinue before conception ! Not safe Methyldopa, Labetolol B/C Drug of choice but side effects Probably safe CCB, Hydralazine C/C Considered safe drugs to add on Probably safe Statin X Discontinue before conception ! Unsafe Take Home Points Maternal and Fetal Outcomes can be improved by consistent intervention before conception Education and counseling in the primary care setting are critical Referral for counseling by Obstetrician Contraception counseling Nutrition counseling and weight management Smoking cessation Pre-natal Vitamin (Folic acid ) Discontinuation of teratogenic drugs Optimal glycemic control:HbA1c 6-6.5% 12

4/12/2018 What is the best Test for Diagnosis of GDM ? Lack of international consensus Confusion over competing diagnostic criteria As of 2018 no unifying approach Variety of regional, institutional diagnostic criteria High prevalence of GDM with One-step test Lack of evidence that treatment of mild GDM results in better outcome ( FPG < 95 mg/dl) Concerns over high cost and harm GDM Screening and Diagnosis 2010 IADPSG 2018 recommends ACOG continues 1973 one-step-approach 2014 USPSTF to support two-step 50-gm 1-hr with 75-gm 2-hr supports Approach with GCT + OGTT universal screen universal screen 3-hrOGTT 2013 Selective 2008 2015 Consensus screen conference: Cochrane Review: HAPO at 24 – 28 No specific screening Lack of weeks Study adequate Strategy has been two-step evidence for approach shown to be optimal one-step, high cost and burden 13