How to manage a pregnant patient with diabetes

Transcription

1 How to manage a pregnant patient with diabetes EASD Postgraduate Course on Clinical Diabetes and its Complications, Shiraz, Iran Rasa Verkauskiene Lithuanian University of Health Sciences 2017

2 History of Glycemia Normalization Programs Infant mortality (%) 100 Joslin < Tyson 1976 Martin 1979 Essex 1973 Jovanovic 1980 Joslin Karlsson 1972 Tyson 1979 Joslin Essex Pedersen 1969 Karlsson DKA DKA=diabetic ketoacidosis Mean maternal blood glucose (mg/dl) Adapted from Jovanovic L, Peterson CM. Diabetes Care. 1980;3:63-68

3 Newborn infant of a diabetic mother Relatively small head circumference Cushingoid appearance. Enlarged heart, liver, Subcutaneus fat tissue. Hypertrophy of the pancreas. J.Pedresen. The pregnant diabetic and her newborn, 1967

4 Risks of diabetes in pregnancy Pre-existing diabetes miscarriage congenital malformation stillbirth neonatal death Gestational fetal macrosomia neonatal hypoglycaemia perinatal death birth trauma (to mother and baby) induction of labour or caesarean section transient neonatal morbidity obesity and/or diabetes developing later in the baby s life

5 Risk to fetus/neonate Macrosomia (birth weight >4000g). Intrauterine death. Traumatic labor and shoulder dystocia. Postnatal morbidity: lung immaturity hypoglycemia hypocalcemia hyperbilirubinemia polycythemia. Implications for childhood and adolescence.

6 The Impact of Maternal Hyperglycemia During Pregnancy Modified Pedersen Hypothesis Placenta Maternal hyperglycemia Fetal pancreas stimulated Insulin Fetal hyperinsulinemia IgG-antibody-bound insulin Insulin resistance syndrome Fetus IgG=immunoglobulin G Mother Pedersen J. Course of diabetes during pregnancy. Acta Endocrinol. 1952;9:

7 Diabetes mellitus associated with pregnancy gestational diabetes mellitus (GDM, 88% ) and preexisting diabetes mellitus Type 1 (4%) Type 2 (8%)

8 The prevalence of pre- and gestational diabetes from 1997 to 2008 Pre-gestational diabetes Gestational diabetes

9 Diabetes in pregnancy should be diagnosed by the 2006 WHO criteria for diabetes if one or more of the following criteria are met in the 1 st trimester of pregnancy fasting plasma glucose 7.0 mmol/l (126 mg/ dl) 2-hour plasma glucose 11.1 mmol/l (200 mg/dl) following a 75g oral glucose load random plasma glucose 11.1 mmol/l (200 mg/ dl) in the presence of diabetes symptoms.

10 Gestational diabetes mellitus should be diagnosed in the 2 nd or 3 rd trimester if one or more of the following criteria are met: fasting plasma glucose >5.1 (92 mg/dl) 1-hour plasma glucose 10.0 mmol/l (180 mg/dl) following a 75g oral glucose load* 2-hour plasma glucose > 8.5 mmol/l (153 mg/dl) following a 75g oral glucose load * there are no established criteria for the diagnosis of diabetes based on the 1-hour post-load value

11 HAPO results in pregnant women 15 research centres 9 countries 75-g GTT in week of pregnancy

12 Po 2 val. GD results indicate strong, continuous associations of maternal glucose levels below those diagnostic of diabetes with increased birth weight and increased cord-blood serum C-peptide levels. GD GD Hyperglycemia and Adverse Pregnancy Outcomes. N Engl J Med 2008;358:

13 IADPSG recommends to classify diabetes in pregnancy as OVERT and GESTATIONAL in ADA accepts the recommendation in WHO published recommendations in Acceptance of FIGO, EBCOG in ACOG: 2 steps strategy

14 Criteria for GDM Glucose (mmol/l) WHO (previous) IADPSG ADA (2011) WHO (2013) NDDG 75g 75g 100g Fasting hr hr hr. 8.0 GDM 1 abnormal value 1 abnormal value 2 abnormal value Increases the prevalence of GDM from 4 to 15-20%

15 WHO recommendations for screening Local health authorities have to specify the screening coverage according to local burden, resources and priorities

16 Risk factors All pregnant women should be screened for GDM, whether by patient history, clinical risk factors High risk Prepregnancy overweight and obesity Positive family history of diabetes Glucose intolerance or personal history of GDM Age >25 years History of macrosomia Glucosuria Polycystic ovary syndrome

17 Recommendation: screening and diagnosis Patients at increased risk for type 2 diabetes should be screened for diabetes using standard diagnostic criteria at their first prenatal visit At 24 to 28 weeks' gestation, all women not known to have diabetes (including high-risk women if the initial testing was normal) should undergo a 75-g OGTT, with diagnosis of GDM based upon the finding of 1 abnormality American Diabetes Association. STANDARDS OF MEDICAL CARE IN DIABETES. Diabetes Care 2017;

18 Routine antenatal screening Test Prevalence HIV 12.3/ live births Hepatitis B 2-3.7% carriage rate Rubella / live births Syphilis 6-25/ Asymptomatic bacteriuria 2-10% Hepatitis C / Major fetal malformations 2-4% Chromosomal trisomies 26.3/10000 GDM 6-14%

19 GDM management Lifestyle modification may control 80-90% of GDM Nutritional therapy Physical activity

20 American Institute of Medicine (IOM) Guidelines Total weight gain (kg) Weekly weight gain in 2 nd and 3 rd trimesters (g) Normal weight Overweight Obese The national Academic Press 2009

21 Diet Body mass index (kg/m 2 ) Caloric intake/kg body weight < >

22 Oral hypoglycemic agents Cross the placenta are not approved or recommended for treatment of GDM Metformin Higher rates of premature birth Sulfonylurea glyburide (glibenclamide) Associated with higher rates of fetal macrosomia and neonatal hypoglycemia

23 ... our findings suggest that metformin, alone or with supplemental insulin, is an effective and safe treatment option for women with gestational diabetes mellitus who meet the usual criteria for starting insulin, and that metformin is more acceptable to women with gestational diabetes mellitus than is insulin. Further follow-up data are needed to establish long-term safety. n engl j med 358;19 may 8, 2008

24 Indications for insulin therapy in GDM glucose level > 5.3 mmol/l before meals > 6.7 mmol/l at two hours after meals by diet alone or by oral hypoglycemic drugs Two or more abnormal measurements over 1 to 2 weeks. Jovanovic L, ed in chief. Medical Management of Pregnancy Complicated by Diabetes. 3rd ed. Alexandria, Va: American Diabetes Association; 2000:

25 Evidence on insulin therapy in pregnancy with diabetes In women with gestational diabetes, an intensive insulin therapy leads to better glycemic control and a better neonatal outcome than a twice-daily regimen Nachum Z, Ben-Shlomo I, Weiner E, etal. BMJ 1999;319:

26 Goals of treatment of GDM The main goal to prevent adverse effects to mother and infant Normalization of glucose levels. Time of testing Blood glucose level Fasting 5.3 mmol/l 1 hr after meal 7.8 mmol/l 2 hr after meal 6.7 mmol/l MBG 5.3 mmol/l

27 Glycemic goals Two-hour postprandial glycaemia < 6.7 mmol/l eliminate the excess neonatal morbidity associated with gestational diabetes One-hour postprandial glycaemia < 7.8 mmol/l reduce neonatal morbidity associated with gestational diabetes Langer 0, Rodriguez DA, Xenakis EMJ, et al. Am J Obstet Gynecol 1994;170: Leikin E, Jenkins JH, Graves WL. Obstet Gynecol 1987;70: Parretti E, Mecacci F, Papini M, et al. Diabetes Care. 2001;24(8): Yogey Y, Ben-Haroush A, Chen R, Rosenn B, Hod M, Langer O. Am J Obstet Gynecol Sep;191(3): de Veciana M, Major CA, Morgan MA, et a I. N Engl J Med 1995;333: Jovanovic-Peterson L, Bevier W, Peterson CM. Am J Perinatol 1997;14: Persson B, Stangenberg M, Hansson U, et al. Diabetes 1985;34(Suppl 2):101-5.

28 Labor and delivery Deliver at term Preference for normal vaginal delivery Consider Cesarean section when estimated fetal weight > 4,000 g Avoid hyperglycemia Recommended glucose levels 3.85 mmol/l 4.9 mmol/l

29 Postnatal care Lifestyle advice A fasting plasma glucose measurement

30 Postpartum Considerations (GDM) Women with previous GDM have. 40% to 60% risk of developing type 2 diabetes in 5 to 15 years 66% risk of GDM in future pregnancies Monitor blood glucose levels. For 1 week postpartum At first postpartum checkup 6-12weeks after delivery (OGTT) Yearly thereafter (FPG) Encourage weight loss if patient is overweight or obese. Provide appropriate referrals if diabetes or IGT diagnosed. American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S88-S90

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32 Pre-existing Diabetes and Pregnancy

33 Diabetes and Pregnancy Type 1 and Type 2 Diabetes Preexisting diabetes diagnosis Preconception care is essential Treat with insulin If untreated during first few weeks gestation, associated with Spontaneous abortion Birth defects If untreated during second or third trimester, associated with Fetal macrosomia Birth injury Maternal hypertension Maternal preeclampsia Future diabetes and/or obesity in child American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S76-S78

34 Type 1 DM: risk of advers pregnancy outcomes for mothers Hypertension Preeclampsia Haemolysis Liver enzymes enlargement HELLP syndrome SC Hypoglycaemia Ketoacidosis Progression of renal failure Progression of retinopathy Adverse pregnancy outcomes in women with Diabetes. Negrato et al. Diabetology & Metabolic Syndrome 2012, 4:41

35 Classification by P. White Class A1: gestational diabetes; diet controlled Class A2: gestational diabetes; insulin controlled Class B: onset at age 20 or older or with duration of less than 10 years Class C: onset at age or duration of years Class D: onset before age 10 or duration greater than 20 years Class F: diabetic nephropathy Class R: proliferative retinopathy Class RF: retinopathy and nephropathy Class H: ischemic heart disease Class T: prior kidney transplant

36 Diabetes in Early Pregnancy (DIEP) Trial Probability of Pregnancy Loss by A1C Status Rate of 30 pregnancy loss (%) Diabetes No diabetes A1C: Standard deviation from control mean Mills JL et al. N Engl J Med. 1988;319:

37 Infant Malformations Are Related to First-trimester A1C Levels, Not Type of Insulin A1C standard deviation from mean at first prenatal visit correlates with major anomaly rate in insulin lispro treated patients (5.4%, P=0.04) Percent with major anomalies < 2 2 to <0 0 to <2 2 to <4 4 to <6 6 to <8 8 A1C standard deviation from mean Wyatt JW et al. Diabet Med [online early]. Available at: links/doi/ /j x/abs/. Accessed December 23, 2004

38 Hyperglycaemia and risk of malformations Pregestational Diabetes Mellitus and Pregnancy. Josip Djelmis, Zeljko Metelko, Ivana Pavlic-Renar, Akkina Suresh Babu, 1999, Croatia

39 Preconception Care of DM Medical Assessment Pregnancy planning!!! Duration and type of diabetes Medical history and current medical management plan Chronic diabetes-related complications Retinopathy Nephropathy (24-hour urine: creatinine clearance, total protein excretion, and microalbuminuria) Neuropathy (Autonomic neuropathy, especially gastroparesis) American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S76-S78

40 Preconception Care of DM Medical Goals Switch from oral agent therapy to physiologic basal-bolus insulin replacement (type 2 diabetes) Folic acid 1-5mg/day Prevent hypoglycemia and ketoacidosis Blood pressure <130/80 mm Hg Protein excretion levels <150 mg/24 hours Free T 4, TSH Establish medical team for ongoing management American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S76-S78

41 Preconception Care of DM Blood Glucose Goals SMBG fasting and postprandial, and preprandial when intensive insulin therapy (u to 7-8 x/day) Fasting/premeal: 4-6 mmol/l 2 hour postmeal: 4-8 mmol/l HbA1c <6.5% Use insulin analogs Early recognition of patients with high risk Severe hypo within last year Hypoglycemia unawareness ADA Diabetes Care 2017 NICE Guidelines 2015

42 Preconception Care of DM Preventing Retinopathy Progression Rapid normalization of blood glucose during pregnancy can trigger retinopathy progression A preconception dilated eye exam should be performed by an ophthalmologist Retinal status should be stabilized prior to conception Reassess retinal status each trimester (more frequently if retinopathy is present) American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S76-S78

43 Care during pregnancy SMBG fasting and postprandial, and preprandial when intensive insulin therapy (u to 7-8 x/day) Fasting/premeal: 4-6 mmol/l 2 hour postmeal: 4-8 mmol/l Ideally HbA1c <6% without severe hypos Reduce insulin dose by 10% at 8-16 GW Avoid supplementary insulin between meals Up to 4 mild hypos per week acceptable ADA Diabetes Care 2017 NICE Guidelines 2015

44 Continuous Subcutaneous Insulin Infusion (CSII) Advantages Programmable bolus dosing decreases risk of Glucose excursions Hypoglycemia Hyperglycemia No need for multiple daily injections Greater diet and lifestyle flexibility Increased patient enthusiasm and contact with health care team Disadvantages Complicated regimen requires high level of patient vigilance Mechanical problems with pump can lead to DKA Increased risk of infection at insertion site Catheter cannot be inserted in abdominal wall; alternate site required Gabbe SG. J Matern Fetal Med. 2000;9:42-45

45 Insulin Delivery Throughout Pregnancy Calculating Daily Insulin Dose Gestational week Insulin dose/current pregnant kg 0.7 U 0.8 U 0.9 U 1.0 U Insulin dose in the 1 st trimester insulin dose weekly/beweekly in the 2 nd /3 rd trim. Basal <50% Bolus >50% Jovanovic L. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker Inc; 2002:

46 Hypertension in diabetic pregnancy Prevalence of hypertension up to 40% both in Type 1 and Type 2 Gestational hypertension 10%? Preeclapmsia :20% defined as hypertension and proteinuria after 20 gestational weeks BP goal / mmhg AEI and ARB contraindicated because of fetal malformations : renal dysplasia, oligohydramnios

47 Recommended drugs to be used in treatment of hypertension in diabetic pregnancy Drug Daily dose (mg) Side effects Methyldopa Drowsiness, hemolytic anemia, elevated liver enzymes Labetolol Bronchospasm Diltiazem (extended release) Nifedipine Tachycardia, headaches Clonidine Prazosin Fetal Bradycardia

48 Insulin management of labor and delivery The usual dose of intermediate-acting insulin is given at bedtime, but the usual morning dose is withheld; protocols of insulin and fluid infusions are used; Suggested maternal glucose target <5.6mmol/l (<100mg/dL) to minimize neonatal hypoglycemia. Medical Medical Management of Pregnancy Complicated Complicated by Diabetes, by ed. Diabetes, Lois Jovanovič, 2009

49 Postpartum Considerations Lactation and Nutrition Breastfeeding is recommended. Maintain pregnancy meal plan or develop postpartum plan to meet added caloric requirements of breastfeeding. Rapid weight loss is not advised; exercise is recommended. Insulin use must be continued if postpartum normoglycemia cannot be maintained otherwise. Blood glucose concentrations may be variable in women with type 1 diabetes.

50 Important!!! Pre-pregnancy counseling. Normoglycemia at conception. Strict control throughout the pregnancy.

51 Multidisciplinary approach to diabetes in pregnancy

52 The team of specialists responsible for the follow-up of a diabetic pregnant woman ENDOCRINOLOGIST NURSE-EDUCATOR OPHTHALMOLOGIST PREGNANT DIABETIC WOMAN DIETOLOGIST OBSTETRITIAN NEONATOLOGIST

53 Hospital of Lithuanian University of Health Sciences: perinatal mortality rate in diabetic pregnancies % , , ,29 17,82 13, ,57 3, Petrenko V., Baliutaviciene D. et al. Medicina 2008, Addtl. data on file

54 Apps on diabetes in pregnancy

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