MARGARITA ISABEL AMOROSO-ARTES, M.D.

DEPARTMENT OF OBSTETRICS & GYNECOLOGY

DAVAO MEDICAL CENTER

DIABETES IN PREGNANCY

OBJECTIVES

Discuss and define Diabetes in pregnancy

Discuss clinical considerations and recommendations

References

William’s Obstetrics

Greasy & Resnik’s Maternal-Fetal Medicine 6th edition

ACOG Compendium 2008

DIABETES

IMPAIRED GLUCOSE TOLERANCE

HOW IS DIABETES IN PREGNANCY CLASSIFIED?

CLASSIFICATION

PREGESTATIONAL OR OVERT

GESTATIONAL

ETIOLOGICAL CLASSIFICATION

TYPE 1A IMMUNE-MEDIATED B CELL DESTRUCTIONTYPE 1B IDIOPATHIC B CELL DESTRUCTIONTYPE 2 MAY RANGE FROM PREDOMINANTLY INSULIN RESISTANCE TO PREDOMINANTLY AN INSULIN SECRETORY DEFECT WITH INSULIN RESISTANCE

GENETIC MUTATIONS IN B CELL FUNCTIONGENETIC DEFECTS IN INSULIN ACTIONGENETIC SYNDROMES-DOWN, TURNERDISEASE OF THE EXOCRINE PANCREAS– PANCREATITISENDOCRINOPATHIES– CUSHING SYNDROME, OTHERSDRUG OR CHEMICAL INDUCED– GLUCOCORTICOSTERIDS, THIAZIDESINFECTIONS– CONGENITAL RUBELLA, CYTOMEGALOVIRUS

CLASS ONSET FASTING PLAS MA GLUCOSE

2 HOUR POSTPRANDIAL GLUCOSE

THERAPY

A1

A2

GESTATIONAL

GESTATIONAL

< 105 MG/DL>105 MG/DL

< 120 MG/DL

<120 MG/DL

DIETINSULIN

CLASS AGE OF ONSET (YR)

DURATION (YR)

VASCULAR DISEASE

THERAPY

B

C

D

F

R

H

OVER 20

10 TO 19

BEFORE 10

ANY

ANY

ANY

<10

10 TO 19

>20

ANY

ANY

ANY

NONE

NONE

BENIGN RETINOPATHY

NEPHROPATHY

PROLIF. RETINOPATHY

HEART

INSULIN

INSULIN

INSULIN

INSULIN

INSULIN

INSULIN

OVERT DIABETES IN PREGNANCY HIGH PLASMA GLUCOSE LEVELS GLUCOSURIA KETOACIDOSIS

RANDOM PLASMA GLUCOSE >200 MG/DL PLUS POLYDIPSIA, POLYURIA AND UNEXPLAINED WEIGHT LOSS OR A FASTING GLUCOSE EXCEEDING 125 MG/DL

HOW SHOULD SCREENING FOR GDM BE ACCOMPLISHED?

ALL PREGNANT PATIENTS

CLINICAL RISK FACTORS ASSOCIATED WITH INCREASED LIKELIHOOD OF GDMAGEETHNICITYOBESITYFAMILY HISTORYPAST OBSTETRIC HISTORY

LOW RISK MEETS ALL THE CRITERIA:

AGE YOUNGER THAN 25 YEARS NOT A MEMBER OF AN ETHNIC GROUP

(HISPANIC, AFRICAN, NATIVE AMERICAN, SOUTH OR EAST ASIAN, PACIFIC ISLANDS ANCESTRY)

BODY MASS INDEX OF 25 OR LESS NO PREVIOUS HX OF ABNORMAL GLUCOSE

TOLERANCE NO PREVIOUS HX OF ADVERSE OBSTETRIC

OUTCOME ASSO. W/ GDM NO KNOWN DIABETES IN FIRST DEGREE

RELATIVE

SCREENING TEST: 50 GM ORAL GLUCOSE CHALLENGE TEST

USE HISTORIC RISK FACTORS TO IDENTIFY THE INDIVIDUALS WHO MAY HAVE SUCH A LOW RISK FOR GDM THAT GLUCOSE CHALLENGE TESTING MAY NOT BE WORTHWHILE

THERE MAY BE GROUPS AT SUCH HIGH RISK FOR GDM THAT IT MAY BE MORE CONVENIENT AND COST EFFECTIVE TO PROCEED DIRECTLY TO THE DIAGNOSTIC GTT WITHOUT OBTAINING THE SCREENING TEST

AT WHAT GESTATIONAL AGE SHOULD LABORATORY SCREENING BE PERFORMED?

PREVALENCE OF GDM INCREASES W/ ADVANCING GESTATION

50 GM, 1 HOUR ORAL GLUCOSE CHALLENGE TEST AT 24-28 WEEKS AGE OF GESTATION

INSULIN RESISTANCE INCREASES AS PREGNANCY PROGRESSES- TESTING LATER IN PREGNANCY WILL YIELD HIGHER ABNORMAL TESTS

PX WITH HX OF GDM PREVIOUS PREGNANCY 30 TO 35% LIKELIHOOD OF RECURRENCE IN SUBSEQUENT PREGNANCY

PXS WITH HX OF GDM SHOULD BE TESTED IN BETWEEN PREGNANCIES TO DETECT PREEXISTING DIABETES

HOW IS LABORATORY SCREENING ACCOMPLISHED?

50 GM, 1 HOUR GLUCOSE CHALLENGE TEST

PURE GLUCOSE LOAD OF 50 GM IN 150 ML OF FLUID

GLUCOSE POLYMER SOLUTIONS

( FEWER GI SYMPTOMS) SENSITIVITY: 80-90% THE SCREENING TEST MAY BE

ADMINISTERED WITHOUT REGARD TO THE TIME ELAPSED SINCE THE LAST MEAL

IS THERE AN APPROPRIATE THRESHOLD VALUE FOR THE LABORATORY SCREENING TEST?

AMERICAN DIABETES ASSOCIATION:

PAST: 140 MG/CL

CURRENT: 130 MG/DL

SENSITIVITY: 79%

SPECIFICITY: 97%

** EITHER THRESHOLD IS STILL ACCEPTABLE***

HOW IS GDM DIAGNOSED?

DIAGNOSTIC TEST SPECIFIC: 100 GM, 3 HOUR ORAL GTT

POSTIVE DIAGNOSIS REQUIRES 2 OR MORE THRESHOLDS BE MET OR EXCEEDED

PXS W/ ONLY ONE ABNORMAL VALUE HAVE INCREASED RISK FOR MACROSOMIC INFANT AND OTHER MORBIDITIES

PXS SHOULD REMAIN SEATED DURING THE TEST

INSTRUCTED TO FOLLOW AN UNRESTRICTED DIET CONSUMING AT LEAST 150 GM OF CHO PER DAY FOR AT LEAST 3 DAYS PRIOR THE TEST TO AVOID CHO DEPLETION WHICH COULD CAUSE SPURIOUSLY HIGH VALUES ON THE GTT

DIAGNOSTIC CRITERIA FOR GDM

STATUS PLASMA OR SERUM GLUCOSE LEVEL CARPENTER/COUSTAN CONVERSION

PLASMA LEVELNATIONAL DIABETES DATA GROUP CONVERSION

MG/DL MMOL/L MG/DL MMOL/L

FASTING 95 5.3 105 5.8

ONE HOUR 180 10 190 10.6

TWO HOURS 155 8.6 165 9.2

THREE HOURS

140 7.8 145 8

HOW SHOULD BLOOD GLUCOSE BE MONITORED IN A WOMAN W/ GDM?

CAPILLARY GLUCOSE MONITORING

Frequency & timing should be individualized

Postprandial have the strongest correlation w/ fetal growth

Typical glucose monitoring:Rising in the morning1 or 2 hrs after breakfastBefore & after lunchBefore dinnerBedtime

Target Capillary Glucose Levels

Fasting plasma glucose level of 90 to 99 mg/dL (5.0 to 5.5 mmol/L)

and 1 hour postprandial plasma glucose

level <140 mg/dL (<7.8 mmol/L)

or 2 hour postprandial plasma glucose

level < 120 to 127 mg/dL (<6.7 to 7,1 mmol/L)

Target Plasma Glucose Values:

Preprandially: 65 to 95 mg/dL

Postprandially: 130 to 140 mg/dL

POSTPRANDIAL GLUCOSE VALUES APPEAR TO BE MOST EFFECTIVE AT DETERMINING THE LIKELIHOOD OF MACROSOMIA AND OTHER ADVERSE PREGNANCY OUTCOMES IN PATIENTS WITH GDM

Recommended Glucose GoalFASTING/PREMEAL <95 MG/DL

1 HOUR POST PRANDIAL 140MG/DL

2 HOURS POST PRANDIAL <120 MG/DL

MEAN PLASMA GLUCOSE 90-100 MG/DL

IS THERE A ROLE FOR DIET THERAPY IN THE TREATMENT OF GDM?

YES NUTRITIONAL INTERVENTION

SHOULD BE STARTED PXS DELIVER FEWER MACROSOMIC

INFANTS AMERICAN DIABETES ASSOCIATION:

OVESE WOMEN (BMI > 30): MODERATE CALORIC RESTRICTION (30-33%)

SUPPLEMENTARY DIETARY FIBER MAY IMPROVE GLYCEMIC CONTROL

IS THERE A ROLE FOR ORAL ANTIDIABETIC AGENTS IN THE TREATMENT OF GDM?

ORAL ANTIDIABETIC AGENTS CONTRAINDICATED

EARLY GENERATION SULFONYLUREAS CROSSES THE PLACENTA STIMULATE FETAL PANCREASE FETAL HYPERINSULINEMIA AND TERATOGENIC

PRINCIPLES OF INSULIN THERAPY

Goal of exogenous insulin therapy during pregnancy: postprandial blood glucose excursions maintained w/in a relatively narrow range (70 to 120 mg/dL)

As pregnancy progresses increasing fetal demand for glucose results in lower fasting & between meal blood glucose levels increasing risk of symptomatic hypoglycemia

Insulin Preparation

Time to Peak Action (Hr)

Total Duration of Action (Hr)

Comment

Insulin Lispro 1 2 Onset w/in 10 mins of injection; no need to delay meal onset after injection

Insulin Aspart 1 2 Onset w/in 10 mins of injection; no need to delay meal onset of injection

Regular Insulin 2 4 Good coverage of individual meals if injected 20 min before eating; increased risk of postprandial hypoglycemia w/ unopposed action 2-3 hr after eating

NPH Insulin 4 8 Provides intermediate acting control; give on rising & at bedtime; risk of 3 am hypoglycemia

Insulin Glargine 5 <24 Prolonged flat action profile; limited pregnancy experience; increased ris of nocturnal hypoglycemia or undertreatment during the day

Period of maximal fetal growth velocity & fat accretion occurs at 33.5 wks gestation

Delay in therapy by 33-34 wks AOG would miss maximal glycemic intervention effective in modulation fetal growth

Allow a 1 to 2 week trial of dietary management

Insulin regiment used should be individualized accordin to the patient’s profile

Short acting insulin (4 to 8 units to start) before meals

If > 10 units of short acting insulin is needed before the noon meal add 6 to 8 doses of NPH before breakfast

Doses are scaled up as necessary

INTRAPARTUM GLYCEMIC MGT Maternal hyperglycemia perinatal

asphyxia & neonatal hypoglycemia Strict maternal euglycemia does not

guarantee newborn metabolic stability in infants w/ macrosomia

Use of combined insulin & glucose infusion durinng labor maintains maternal plasma glucose level in narrow range (80 – 110 mg/dL)

-- reduces incidence of neonatal hypoglycemia

Typical infusion rates5% Dextrose in Ringer’s lactate at 100

ml/hour ANDLispro or aspart insulin at 0.5 to 1 units per

hour CBG monitored q hourly For patients with diet controlled GDM

avoiding dextrose in all IV fluids during labor maintains excellent glucose control

For CS

Procedure should be performed early in the day to avoid prolonged fasting

Night before surgery: instructed to take full dose of NPH or

glyburideNo morning insulin or glyburide should be

taken

Postpartum Metabolic Mgt In the Recovery Room & after delivery

Insulin subcutaneously

Insulin dose required after delivery typically 30 to 50% of the preprandial doses required during pregnancy just before delivery

IS FETAL ASSESSMENT INDICATED IN PREGNANCIES COMPLICATED BY GDM?

Antepartum fetal testing recommended

3rd trimester Goal mgt: prevent stillbirth adn asphyxia while optimizing the opportunity for safe vaginal delivery

Monitoring fetal growth to determine proper timing & route of delivery and testing for fetal well being at frequent intervals

PRECONCEPTION Maternal glycemic control

8-10 WKS Sonographic crown rump measurement

16 WKS Maternal serum AFP

20-22 WKS High resolution sonography, fetal cardiac echocardiography in women in suboptimal diabetic control at first prenatal visit

24 WKS Baseline sonographic growth assessment of the fetus

28 WKS Daily fetal movement counting by the mother

32 WKS Repeat sonography for fetal growth

34 WKS Biophysical testing: 2x weekly NST or weekly CST or weekly BPS

36 WKS Estimation of fetal weight by sonography

37-38.5 WKS Amniocentesis & delivery for pxs in poor control

38.5-40 WKS Delivery w/o amniocentesis for pxs in good control who have excellent dating criteria

Fetal movement counting

1. Count the baby’s movement EVERY NIGHT2. A movement may be a kick, swish or roll. Do not count hiccups or

small flutters3. You can start counting any time in the evening when the baby is

active. BUT: COUNT EVERY NIGHT4. Count the baby’s movement while lying down, preferable on the left

side5. Mark down the time the baby’s movement felt for the first time6. Mark down down the time the baby’s movement felt for the tenth

time7. Should feel at least 10 fetal movements within one hour. Be

alarmed if

a. No 10 fetal movements with 1 hourb. It takes longer and longers for the baby to move ten timesc. Have not felt the baby move all day

When and how should deliveries be accomplished in patients with GDM?

Timing of delivery should minimize neonatal morbidity & mortality while maximizing the likelihood of vaginal delivery

Optimal time for delivery: 38.5 to 40 weeks

Labor or Cesarean?ACOG recommended primary cesarean for diabetic

gravidas with EFW greater than 4500 gm to reduce risk of shoulder dystocia

Indications for delivery in diabetic pregnancy

TYPE INDICATION

FETAL Nonreactive, + CSTReactive, + CST, mature fetusSonographic evidence of fetal growth arrestDecline in fetal growth ratge w/ decreased AFI40-41 wks AOG

MATERNAL Severe preeclampsiaMild preeclampsia, mature fetusMarkedly failing renal function

OBSTETRIC Preterm labor with failure of tocolysisMature fetus, inducible cervix

Confirmation of fetal maturity before termination of pregnancy

Phosphatidylglycerol >3% in amniotic fluid colleted from the

vaginal pool or by amniocentesis

Completion of 38.5 weeks gestation

Normal last menstural period

First pelvic exam before 12 wk confirms dates

Sonogram before 24 wk confirms dates

Documentation of more than 18 wk of unamplified (fetoscope) fetal heart tones

Should women with a history of GDM be screened postpartum?

Women w/ a history of GDM are at increased risk developing diabetes (generally type 2) later in life

What are the fetal effects of GDM?

Fetal Effects

Abortion Preterm Delivery Malformations Unexplained Fetal Demise Hydramnios

Fetal Death In pregnancies not receiving optimal

care After 36 wks gestation in pxs w/

Vascular diseasePoor glycemic controlHydramniosFetal macrosomiaPreeclampsia

Chronic hypoxia as likely cause of fetal death

Anomaly Incidence

Caudal regression

Situs inversus

Spina bifida, hydrocephaly, or other CNS defect

Anencephaly

Heart Anomalies

Anal/rectal atresia

Renal Anomalies Agenesis Cystic Kidney Duplex ureter

252

84

2

3

4

3

5

44

2.3

Neonatal Effects

Respiratory distress Hypoglycemia Hypocalcemia Hyperbilirubienmia Cardiac Hypertrophy Long Term Cognitive Development Inheritance of Diabetes Altered Fetal Growth

What are the Maternal Effects

Diabetic Nephropathy Diabetic Retinopathy Diabetic Neuropathy Preeclampsia Ketoacidosis Infections