DIABETES IN PREGNANCYDIABETES IN PREGNANCY

Josephine Carlos-Raboca, MD

• Pregnancy is a time when Pregnancy is a time when serial metabolic changes serial metabolic changes in the mother are carefully in the mother are carefully regulated to provide regulated to provide optimum substrate to optimum substrate to mother and fetus. mother and fetus.

GOALS:GOALS:Normal outcome of index pregnancy.Decrease risk for abnormal glucose and

insulin homeostasis.Mother (before, during, after pregnancy).Infant subsequent generations.

Gestational Diabetes Mellitus Gestational Diabetes Mellitus (GDM)(GDM)

Any degree of glucose in tolerance with onset or first recognition during pregnancy.

4th International Workshop-Conference on GDM, 1998.

Pregestational Diabetes MellitusPregestational Diabetes Mellitus

Diabetes diagnosed before pregnancy.

PrevalencePrevalence of GDMof GDM

1 – 14%USA--- 3-5%MMC (Asian Population)

– Raboca et al 13.4%

Perinatal Complications:Perinatal Complications:MacrosomiaRespiratory Distress Syndrome (RDS)HypocalcemiaHyperbilirubinemiaHypoglycemiaPolycythemia

Congenital MalformationsCongenital Malformations

SkeletalCardiac (septal and outflow tract lesions)CNS and neural tube defectsGastrointestinal DefectsGenitourinary Tract lesions

Maternal and Fetal Factors of Maternal and Fetal Factors of TeratogenesisTeratogenesis

Genetic Background Teratological Period Disturbances in Maternal-Fetal Transport Concentrations of Metabolites Hyperglycemia Hyperketonemia Somatomedin inhibitors Arachidonic/myoinositol deficiency Generation of free oxygen radicals Genotoxity

Teratology 1997

Objectives:Objectives:1. Recognize GDM2. Know how to provide nutritional plan3. Know how to give insulin4. Discuss preconception and postpartum

care5. Recognize special problems of

pregestational diabetes

Case ICase I

31 year old female G1 PO, Age of Gestation 20 weeks Weight gain of 5 kg in the last 4 weeks BMI (pre-pregnant) = 30 Height: 165 cm actual body weight 90 kg Family History (+) DM in mother

• Would you recommend Would you recommend testing for GDM at this testing for GDM at this time time or later at 24or later at 24thth to 28 to 28thth weeks of gestationweeks of gestation

Risk Factors of GDMRisk Factors of GDMAge > 25 years of ageObesity – BMI > 27 kg/m2 or > 20% over

DBWFamily History of diabetes in first degree

relativeEthnicity (Hispanic American, Native

American, Asian American, Pacific Islander)

ADA 2001ADA 2001

– Low risk – no test– Average risk – test at 24th-28th

week– High risk – test at 1st visit if

negative repeat at 24 – 28 weeks.

ASGODIP– Test at 1st visit and every

trimester if negative in previous test

50 gm glucose challenge test was 150 mg/dl

100 gm OGTT F=102; 1H=192; 2H=155; 3H=140

Does this patient have GDM?

Diagnosis of GDMDiagnosis of GDM 100 gm OGTT 75 gm OGTT mg/dl mml/L mg/dl mml/LF 95 5.3 95 5.31H 180 10.0 180 10.0 2H 155 8.6 155 8.63H 140 7.8 > 2 values met = GDM

ASGODIP, WHOEuropean Diabetes Policy Group 1992-1998 75 gm OGTT, 2H >140

Prescribe diet for this patientPrescribe diet for this patientFor normal weight – 30 kcal/kg of

Present BWFor overweight – 24 kcal/kg of Present

BW For morbidly obese – 12 kcal/kg Present

BW3 meals, 3 snacks, 40% of total calories

= CHO Medical Management of Pregnancy

Complicated by Diabetes

1. With diet, preprandial capillary blood glucose level were 70 - 80 mg/dl,2HPPCBG 95 – 115 mg/dl

2. Would she require insulin?

ADA 2001ADA 2001Insulin Required if diet fails to maintain glucose at following levels. Fasting whole blood glucose < 95 mg/dl (5.3 mml/L) Fasting Plasma Glucose < 105 mg/dl (5.8 mml/L) OR 1H Postprendial whole blood glucose < 140 mg/dl (7.8 mml/L) 1H Postprendial Plasma Glucose < 155 mg/dl (8.6 mml/L) OR 2H Postprandial whole blood glucose < 120 mg/dl (6.7 mml/L) 2H Postprandial Plasma Glucose < 130mg/dl (7.2 mml/L)

1. How would you follow up this patient Postpartum?

2. What are her chances of developing diabetes?

75 gm OGTT > 6 wks. postpartum FPG every year x 3 years

50% in 20 years time50% in 20 years timePredictors of DMPredictors of DM

maternal obesity fasting hyperglycemia duration of time from

index pregnancy

TRIPODTRIPOD

Case 2Case 2 28 years old Go Po

diabetic X 1 year

desires pregnancy

When is the best time for

patient to get pregnant? What advise would you

give her?

Counseling about risk of malformation with poor control

Use of low dose estrogen progestogencontraceptive till good metabolic control isachieved.

Goals:

HBA is 1% above normal Preprandial CBG 70-110 mg/dl (3.9-5.6mml/L)

CPG 80-110 mg/dl (4.4-6.1 mml/L) 2H Postprandial CBG < 140 mg/dl (7.8mml/L)

CPG < 155 mg/dl (8.6mml/L)

4-7 X / day4-7 X / day preprandial preprandial 1 hour or 2 hour post prandial 1 hour or 2 hour post prandial

What other medical What other medical problems should you problems should you consider in a diabetic consider in a diabetic pregnant?pregnant?

Acceleration of retinopathy Pregnancy induced hypertension Progression of Nephropathy

What is your goal for glycemic What is your goal for glycemic control during labor?control during labor?

120 mg/dl D5 0.45 NSS at 100-125 ml/hour CBG every 1-4 hours Insulin infusion to start at

1unit/hour of regular insulin if CBG > 120 mg/dl

THANK YOU.THANK YOU.

HYPERGLYCEMIA AND HYPERGLYCEMIA AND ADVERSE PREGNANCY ADVERSE PREGNANCY

OUTCOME STUDY (HAPO)OUTCOME STUDY (HAPO)

Background: Overt diabetes clearly increases the risk of adverse pregnancy outcome

What level of glucose intolerance short of diabetes increases the risk of adverse pregnancy outcome?

Study protocolStudy protocol

75gm OGTT 24-32 weeks (average 28) 0,1,2 hours

Venous plasma, enzymatic methodResults provided if FPG> 105 (5.8)

2 hour > 200 (11.1)any value <45(2.5)

otherwise blinded to caregivers

EndpointsEndpoints

Relationship between maternal hyperglycemia and cesarian rate

macrosomia rate fetal hyperinsulinemia neonatal obesity (skinfold thickness) neonatal hypoglycemia rate other morbidities

Study ProtocolStudy Protocol Routine prenatal care Daily kick count from 28 weeks Random venous plasma glucose at 34-37 weeks if

> 160 mg/dl (8.9) or <45 Umbilical cord glucose and C-peptide levels Routine neonatal care Neonatal blood glucose at 1-2 hours of age First feeding 2 hours after birth (may nurse earlier

if desired)

Interim Study ReportInterim Study Report

Enrollment: 9396 womenDeliveries:5282

primary CS 14.5% repeat CS 7.3% prenatal loss 5.5/1000

Number of OGTT: 7160Unblinded: 158 (2.2%)

Interim…Interim…

Glucose levels

FPG 10% > 901 hour 15% > 1602 hour 4% > 140

SummarySummary

Preliminary data from HAPO enrollees confirm the safety of the study protocol and yielded the predicted prevalence of “lesser degrees”of glucose intolerance that should permit an adequate test of the study hypothesis.

Study HypothesisStudy Hypothesis

Hyperglycemia in pregnancy less severe than overt diabetes is associated with increased risk of adverse maternal fetal and neonatal outcomes that is independently related to the degree of metabolic disturbance.