Diabetes in Pregnancy. Maternal Complications: Retinopathy Type 1 diabetes: may be longstanding; control at conception may be suboptimal; …
Diabetes in Pregnancy Diabetes in Pregnancy
Diabetes is the most common endocrine disorder complicating pregnancy, affecting 3 to 5 of all pregnancies:
Pregestational 10
Type 1 IDDM; Type 2 NIDDM
Irene M OShaughnessy, MD, FACP Professor Division of Endocrinology Medical College of Wisconsin
Gestational 90
40 will develop Type 2 diabetes later in life
Diabetes in Pregnancy Before Insulin
Duncan, London 1882
22 pregnancies in 16 women
4 died at the time of labor 7 died within 2 years of delivery 50 of the children were stillborn/neonatal deaths
Diabetes in Pregnancy Before Insulin
DeLee subsequently recommended termination of all pregnancies complicated by diabetes The Principles and Practice of Obstetrics, 1st edition, 1913 Joslin 1915 did not agree with this philosophy
Williams 1909
50 maternal mortality 50 perinatal mortality among survivors
Class
A B
Description
Abnormal GTT at any age or of any duration treated by diet only
Onset at age 20 or older and duration of less than 10 yrs Onset at age 10-19 yrs or duration of 1-19yrs Onset before age 10, duration of over 20 yrs, BDR, or HTN D1 D2 D3 D4 D4 Onset before age 10 Duration of over 20 yrs Calcification
of vessels of leg macrovasc disease Benign retinopathy microvascular disease Hypertension not preeclampsia Proliferative retinopathy or vitreous hemorrhage Nephropathy with over 500 mg/d proteinuria Criteria for both classes R and F Many pregnancy failures Evidence of arteriosclerotic heart disease Prior renal transplantation Diet-controlled GDM Insulin-treated GDM
Diabetes in Pregnancy
With the use of insulin, maternal mortality decreased dramatically Perinatal mortality remained high
This lead to a practice of hospitalization during the latter weeks of pregnancy and cesarean delivery approximately 2 weeks before the estimated date of delivery Modified Whites Classification of diabetes in pregnancy
C D
R F RF G H T Gestational DM A1 A2
White 1949 published a classification system, which is still used today
Diabetes in Pregnancy
Maternal complications Obstetric complications Fetal complications Neonatal complications
Diabetes in Pregnancy
Maternal Complications: Retinopathy
Factors which may contribute to worsening retinopathy
Hypertension Hyperglycemia Rapid normalization of glucose Duration of diabetes State of retina at onset of pregnancy
Diabetes in
Pregnancy
Maternal Complications: Nephropathy Prevalence during pregnancy 5-10 Increases risk for maternal and fetal morbidity Increased risk for perinatal mortality Significant risk of maternal preeclampsia Pre-maturity and fetal growth restriction
Diabetes in Pregnancy
Obstetric complications
Preeclampsia/pregnancy-induced hypertension Chronic hypertension Hydramnios Pyelonephritis Preterm birth C-Section birth Post C-Section infectious morbidity
Diabetes in Pregnancy
Fetal complications Spontaneous abortion Congenital anomalies Macrosomia Fetal growth restriction Fetal death
Major Congenital Malformations in Infants of Diabetic Mothers
Anomaly Skeletal
Caudal regression Spina bifida 3 6 4 4 5 4 6 6
Timing of Malformation weeks from conception
Neural
Anencephaly Myelocele Hydrocephalus
Cardiovascular
Dextrocardia Ventricular septal defects
Renal
Renal agenesis/ hypoplasia
Preconception Care and Prevention of Major Congenital Malformations
Study
Clinical Trial
Fuhrmann, et al 1983-84
Diabetes in Pregnancy
Neonatal complications
Preterm birth RDS Hypoglycemia; hypocalcemia Hyperbilirubinemia Polycythemia Birth trauma
Cardiomyopathy
Year
Preconception Care No Preconception Care Malformations 11 0 49 14 12 10 0 16 Malformations 66 97 90 104 109 82 66 65
Goldman, et al Mills, et al Steel, et al Kitzmiller, et al
Community Trial
1986 1988 1990 1991 1989 1991 1993
Damm, et al Cousins Wilhoite, et al
Background rate of major congenital malformations in nondiabetic pregnancies:2-4
45 40
Reduced Infant Mortality: 1925-Present
Joslin 1922 Joslin 1924 to 1938
Diabetes in Pregnancy: a spectrum of issues
Type 1 diabetes: may be longstanding; control at conception may be suboptimal; complications may be present Type 2 diabetes: may be undiagnosed until woman comes to 1st OB visit late 1st trimester Gestational diabetes: first diagnosed in 3rd trimester
Infant Mortality
35 30 25 20 15 10 5 0 1925 1935 1945 1955 1965 1975 1985 Present
Essex 1951 to 1955 Pederson 1969 Joslin 1956 to 1975
Time
Adapted from Gabbe S et al; Obstet Gynecol 2003 Oct;1024:857-68
Pre-Existing Diabetes: Type 1 and Type 2 Diabetes
Pre-conception counseling promotes better outcomes
Importance of frequent monitoring Hypo and hyperglycemia treatment protocols Nutrition and exercise Intensive management
Discontinue glargine
Preconception Diabetes Management
Intensify blood sugar monitoring to a minimum of premeal and hs Achieve optimal HbA1C of 65-70 Establish presence and extent of complications Consider preconception counseling with perinatologist Optimize and intensify insulin regimen
3-4 injections per day Initiate and/or optimize insulin pump therapy
Patients with Type 1 diabetes who have been reluctant in the past may now consider pump therapy
Diabetes Management During Pregnancy
Begin intensive management as early after conception as possible begins earlier than obstetric care Establish regular frequent office visits and/or phone contact Educate regarding carbohydrate counting and exercise Instruct family members regarding the treatment of severe hypoglycemia glucagon
Blood sugar monitoring
Preprandial tid 2-h postprandial tid Bedtime 3AM occasional
Blood Glucose Goals
Commonly followed guidelines:
Fasting and pre-prandial 1 hour after meals Middle of the night 60 - 90 mg/dl 120 mg/dl 70 130 mg/dl
Preprandial vs Postprandial
In a pregnant patient with Type 1 DM, postprandial SMBG can:
Reduce the incidence of preeclampsia 3 vs 21 Improve success
in achieving glycemic control targets HbA1c and fructosamine Result in smaller neonatal triceps skin-fold thickness 45 vs 51mm Rapid acting insulin analogues are superior to Regular for controlling pp blood sugars
Published guidelines:
Fasting and before meals 1 hour after meals 2-hour postprandial 95 mg/dl 53 mmol / L 140 mg/dl 78 mmol / L 120 mg/dl 67 mmol / L
Adapted from Jovanovic L et al; Endocr Pract 1996; 2: 13-143 Kjos SL et al; NEJM 1999; 34123: 1749-1756
Postprandial Glucose and Macrosomia 9 lbs
Risk of Macrosomia 80 70 60 50 40 30 20 10 0
90 10 0 11 0 12 0 13 0 14 0 15 0 16 0 17 0 18 0 75 80 85
DCCT: Pregnancy Outcomes
Intensive Therapy 14 12 Conventional Therapy
180 women completed 8 270 pregnancies 191 live births 6
4 2 0
HbA1c before HbA1c during Congenital malformations n Spontaneous abortions
10
One Hour Postprandial Blood Glucose
Congenital malformations are preventable
Adapted from Jovanovic L et al; Am J Obstet Gynecol 1991; 164:103 Adapted from Am J Obstet Gynecol 1996;174:1343-1353
U-500 Insulin
5 times more concentrated than U-100 Regular insulin May last up to 24 hours Consider in patients who have severe insulin resistance require 200
units of insulin per day
Rapid-Acting Insulin Analogues vs Regular Insulin
Insulin Analogues vs Human Insulin
Correlations of Receptor Binding and Metabolic and Mitogenic Potencies of Insulin Analogs Designed for Clinical Use
Peter Kurtzhals, Lauge Schäffer, Anders Sørensen, Claus Kristensen, Ib Jonassen, Christoph Schmid, and Thomas Trüb
Diabetes 49:9991005, 2000
Receptor binding affinity and mitogenic potency of insulin analogs relative to human insulin
The results presented in this study show that the amino acid modifications in the 2 rapid-acting insulin analogs, lispro and aspart, had no significant influence on metabolic or mitogenic potency In contrast, the 2 longacting analogs, insulin detemir and insulin glargine, both showed in vitro properties that differed significantly from human in 
sulin The clinical safety implications of the elevated IGF-I receptor affinity and mitogenic potency of insulin glargine are not clear
Diabetes 49:9991005, 2000
Diabetic Medicine 2008;25:165-169
Diabetic Medicine 2008;25:165-169
Intensive Diabetes Management Increases the Risk of Hypoglycemia
Occurrence of severe hypoglycemia 15 times higher in diabetic pregnancies Consequence:
Long-term effects include neuropsychological defects
Hypoglycemia and Diabetic Pregnancies
In a study of 85 patients
41 had an episode of severe hypoglycemia of which 25 became unconscious or needed assistance 84 of the episodes occurred during the first 20 weeks gestation 77 of the episodes occurred at night
Adapted from Ter Braak EW et al; Diabetes Metab Res Rev 2002; 182: 96 105
Adapted from Kimmerle R et al; Diabetes Care 1992:154:1034-37
Managing Diabetes in Pregnancy
How should the patient receive her insulin? CSII vs MDI
CSII provides better glycemic control More flexible lifestyle Better HbA1c Comparable health care costs
Insulin Requirement Throughout Pregnancy
Weeks 3-7 18 increase in insulin requirement related in part to intensification of insulin regimen 9 decrease in insulin requirement with risk of hypoglycemia
Weeks 7-12
Pre-conception insulin dose is roughly 06 units / kg / day
Adapted from Gabbe SG et al; Am J Obstet Gynecol 2000;1826: 1283-91
Insulin Requirement Throughout Pregnancy
Weeks 12-24 Weeks 25-38 Slight increase but fairly stable insulin requirement Progressive increase in insulin requirement associated with insulin resistance
Maximum insulin regimen may be 2-3xs pre-pregnancy dose
Insulin Requirements Throughout Pregnancy
Recommended Medical Monitoring of Pregnant Diabetic Mother
Important Tests for Monitoring Concomitant Diseases and Glucose
Type 2 Diabetes and Pregnancy
Oral hypoglycemic agents should be discontinued as soon as pregnancy is suspected and insulin treatment initiated If pregnancy is planned, patients can be managed on insulin preconception with optimization of glycemic control
Test
Eye examination Kidney function Thyroid function HbA1c Self-blood glucose monitoring Blood pressure weight
Frequency
Prior to conception and then once each trimester Prior to conception and then once each trimester Prior to conception and then once each trimester Prior to conception and once every 2 4 weeks Before meals and 2 hours after meals Prior to conception and at each visit
Adapted from Jovanovic L et al; Insulin Therapy Chap 10; 139-151
Type 2 Diabetes and Pregnancy contd
Goals for therapy similar to GDM and Type 1 diabetes with diet playing a key role Insulin requirement is usually very high
Type 2 Diabetes and the Postpartum Period
Oral agents can usually be restarted unless patient
chooses to breastfeed First generation oral SU agents cross into breast milk but not glyburide Metformin is excreted into breast milk in very small amounts mean milk:serum ratio 063 No studies to date on TZDs and breast milk In small studies, no detrimental effects in infants of mothers treated with SU or metformin
What About Gestational Diabetes?
Two to five percent of all non-diabetic pregnant women develop GDM Forty percent with GDM who are also obese before pregnancy develop type 2 diabetes within four years
Gestational Diabetes GDM
Definition: glucose intolerance of variable severity with onset or first recognition during pregnancy Caused by placental hormones such as estrogen, cortisol and human placental lactogen HPL which cause insulin resistance As the placenta grows, insulin resistance increases and hyperinsulinemia occurs If the pancreas can no longer compensate, GDM results
Adapted from ADA website; Diabetes Statistics 2004
Risk Factors for GDM
Family history of diabetes Maternal age greater than 25 Maternal obesity Previous history of GDM Previous history of poor obstetric outcome High risk ethnic group
Screening for GDM
Occurs at 24 to 28 weeks
OSullivan test: 50 gm glucose challenge irregardless of fasting 1 hour value greater than 130 is abnormal
Rule of 15 in GDM
15 of pregnant women will have an abnormal OSullivan test 15 with positive screen will have an abnormal GTT 15 of patients with GDM will require insulin 15 of patients with GDM will have a macrosomic infant
GDM: Glucose Tolerance Testing
Time h 0 1 2 3 100-g, 3-h Test ADA 95 180 155 140 75-g, 2-h Test WHO 95 180 155
Longterm Outcome of GDM
GDM and Adverse Obstetrical Outcomes
Fetal Macrosomia Preeclampsia Shoulder dystocia Stillbirth Increased rate of C-section
Risk of GDM during subsequent pregnancies 30-70 Risk of Type 2 diabetes 40 at 15 years
Rate of Macrosomia Tri-Toronto Hospital Gestational Diabetes Project
Glucose-tolerant women Untreated women with GDM Treated women with GDM 14 29 10
Dietary Recommendations
With the appropriate diet, 75-80 of women with GDM can achieve normal glycemia
Total Calorie Recommendations in GDM
IBW 80-120 Total Calories 30 calories/kg present pregnant weight PPW 24 calories/kg PPW 12-15 calories/kg PPW
Oral Antidiabetic Agents
First generation SUs Tolbutamide and chlorpropamide cross the placenta
Can cause fetal hyperinsulinemia, Can lead to fetal macrosomia Can result in prolonged neonatal hypoglycemia
121-150 151
There is minimal information regarding the effects of TZDs on fetus
Oral agents continued
Glyburide appears to be safe in pregnancy passage through placenta is very low, probably due to high protein binding Metformin appears to be safe in pregancy Oral agents are not as effective as insulin in all women Oral agents are not FDA approved for use un pregnancy
Insulin Therapy: Gestational Diabetes
Carbohydrate intolerance is major metabolic disturbance Insulin regimen varies depending on severity of hyperglycemia
premeal short-acting insulin analogue with hs NPH insulin Premixed insulin bid
Team approach
Multidisciplinary team assembled to provide timely and comprehensive care Quick response team concept
Anticipate increasing insulin requirement as third trimester progresses
Adapted from Simmons D et at; Diabetes Care 2001; 2412: 2078-2082
Team in Action
3-h OGTT performed in Endocrine Diagnostic Unit Results interpreted while patient is present If abnormal, patient views video on GDM Sees RN CDE same day; RD CDE if possible otherwise
scheduled within one week
Role of RN CDE
Provides and teaches use of meter; provides guidelines for blood glucose monitoring FBS and 2h pp tid If RD CDE is not available, RN CDE provides basic dietary guidelines until patient returns for formal RD CDE visit At 2nd or 1st visit, depending on needs:
Procedure for insulin injection Hypoglycemia education Support and reassurance Ongoing phone support
RD CDE
Provides nutrition guidelines for patient Total carbs should be 40-45 of total calories 2000-2200 typical calorie needs during pregnancy 1 carbohydrate contains 4 cal/g: Example: 2000 x 40 200g CHO per day BR: 45-60 Lunch:45-60 PM:45-60 AM Snack:15 PM Snack:15 HS Snack:15
Models of Care for the Pregnant Diabetic Patient
Comprehensive diabetes and obstetric care provided within perinatology clinic Diabetes care within subspecialty medicine clinic in collaboration with obstetrician
Froedtert Endocrine Diabetes in Pregnancy Clinic
Staffed by an MD with CDE team backup Pts seen every 2 weeks for the entire pregnancy Frequent adjustments made in treatment regimen Regular communication with obstetrician Counseling regarding management of diabetes during labor
Guidelines for postpartum management, including repeat OGTT at 6 weeks postpartum for high risk patients with GDM
Conclusion: Diabetes in Pregnancy
Early diagnosis, aggressive intervention and close follow-up during pregnancy can make a major impact on prevention of complications in both mother and baby
Source:diabetesincontrol.com
