DM IN PREGNANCY

BY Dr. EYOB A.
May 2014.
 Diabetes Mellitus and Pregnancy
• Diabetes mellitus is the most common medical
complication of pregnancy.
• DM during pregnancy can be pregestational ( type I or type
II) or gestational (GDM).
• Gestational diabetes mellitus (GDM) is defined as any
degree of glucose intolerance with first recognition during
pregnancy.
 Carbohydrate Metabolism during
Pregnancy

• Insulin resistance increases as gestation advances, mainly

due to anti-insulin signals (HCG, HPL, progesterone,
estrogen, prolactin, and cortisol) produced by the placenta.
• Human placental lactogen (hPL) is the hormone mainly
responsible for insulin resistance and lipolysis.
• The net effect is to favor placental transfer of glucose to
the fetus and to reduce the maternal use of glucose.
• Ongoing pregnancy is characterized by increasing
resistence and increasing need for insulin.
• GDM occurs when a woman's pancreatic function is not
sufficient to overcome the insulin resistance.
 Pregestational Diabetes

• Pre gestational or overt type I or type II DM occurs in 0.3 to

0.8% of all pregnant women.
• Pre gestational or overt diabetes has a significant impact on
pregnancy outcome.
• The embryo, the fetus, and the mother experience
complications attributable to diabetes.
• The likelihood of successful outcomes is related to the degree
of glycemic control, the degree of underlying cardiovascular
or renal disease.
 Diabetes Mellitus
- Fetal Complications -

• Prenatal complications

- The risk for spontaneous abortion is tripled in cases with glycosylated

hemoglobin (HbA1c) level > 12%.

- The frequency of malformations in children of diabetic women is three to four

times higher than in controls.

- The occurrence of malformations is strongly correlated to blood glucose and

HbA1c levels.
 Diabetes Mellitus
- Congenital Malformations-

• It is the most important cause of perinatal loss.

• There is a two fold to six fold increase in major malformations
in infants of type 1 and type 2 diabetic mothers.
• The insult that causes malformations in IDM affects most
organ systems and must act before the 7th week of gestation.
• Cardiac anomalies are the most common malformations with
IDM.
• The congenital defect thought to be most characteristic of
diabetic embryopathy is sacral agenesis or caudal dysplasia.
Teratogenesis
 Diabetes Mellitus
- Prenatal Complications -

• Common malformations in diabetic pregnancy

- CNS: Anencephaly, encephalocele, meningomyelocele, holoprosencephaly,

microcephaly
- Heart: Transposition of the great arteries, ventricular septal defects, atrial
septal defects, hypoplastic left ventricle, situs inversus.
- Skeletal: caudal regression syndrome (sacral agenesis), neural tube
defects.
- Renal: Absent kidneys, polycystic kidneys, double ureter.
- Gastrointestinal: Tracheoesophageal fistula, bowel atresia.
 Diabetes Mellitus
- Prenatal Complications -
• Both explicable and unexplained still birth occur with increased
frequency.
• Explicable stillbirths are due to placental insufficiency in patients
with poor glycemic control.
• Unexplained Fetal Demise:
– Stillbirths without identifiable causes are a phenomenon
relatively unique to pregnancies complicated by overt
diabetes.
– They are "unexplained" because obvious cause of fetal death
are not apparent.
– These infants are typically large-for-gestational age and die
before labor, usually at 35 weeks or later.
 Diabetes Mellitus
- Fetal Peripartal Complications -

• Fetal macrosomia is defined as a birth weight above the 90th

percentile according to population-specific growth curves.
• Macrosomia has been observed in as many as 50% of
pregnancies complicated by GDM, and 40% in preexisting
diabetes mellitus.
• Growth of Infants of mothers with GDM is disproportionate, with
chest-to-head and shoulder-to-head ratios large.
• The disproportionate growth contribute to the higher rate of shoulder
dystocia traumatic birth injury, and asphyxia.
Two extremes of growth abnormalities in pregnancies
complicated by diabetes mellitus
The modified
Pederson
hypothesis
According to the Pedersen
hypothesis, maternal
hyperglycemia results in
fetal hyperglycemia and
hyperinsulinemia, resulting
in excessive fetal growth
 Diabetes Mellitus
- Fetal Postnatal Complications -

- Maternal hyperglycemia leads to Islet cell hyperplasia of the

fetus which leads to exaggerated insulin release following
delivery, causing neonatal hypoglycemia (blood glucose level <
40 mg/dl) during the 1st day of life.
- The degree of hypoglycemia of the newborn is dependent on
the maternal glucose control during the later half of the
pregnancy and during labor.
- The frequency of this complication ranges from 20 to 50% and is
most pronounced on the 1st 12 hours of life.
 Diabetes Mellitus
- Fetal Postnatal Complications -

Respiratory distress syndrome

occurs more often in children of diabetic mothers, especially when
they are born prematurely.
Pulmonary function in newborns is decreased because of
hyperinsulinemia.
insulin can interfere with substrate availability for surfactant
biosynthesis.
 Maternal Effects

• With the possible exception of diabetic retinopathy, the long-

term course of diabetes is not affected by pregnancy.
• Maternal death rates in women with diabetes is increased ten
fold.
• Deaths most often result from ketoacidosis, hypertension,
preeclampsia, and pyelonephritis.
 Diabetes Mellitus
- Maternal Complications-
• Preeclampsia
– Most often forces preterm delivery in diabetic women.
– Special risk factors for preeclampsia include any vascular
complications and preexisting proteinuria, with or without chronic
hypertension.
– The risk of preeclampsia is 11 % in class B, and 36 – 54 % in classes F-
R.
 Diabetes Mellitus
- Maternal Complications-

• Diabetic Ketoacidosis:
– It affects approximately 1 percent of diabetic pregnancies,
– It may develop with hyperemesis gravidarum, beta -
mimetic drugs given for tocolysis, infection, and
corticosteroids given to induce fetal lung maturation.
– The incidence of fetal loss is about 20 percent with
ketoacidosis.
– Pregnant women usually have ketoacidosis with lower
blood glucose levels than when nonpregnant.
 Diabetes Mellitus
- Maternal Complications-
• Infections:
– Almost all types of infections are increased in diabetic
pregnancies.
– Common infections include candida vulvovaginitis, urinary
infections, respiratory tract infections, and puerperal pelvic
infections.
 Diabetes Mellitus
- Maternal Complications -
• Renal disease (diabetic nephropathy)
- 5 to 10% of diabetic women will experience renal disease
- Symptoms are: reduced creatinine clearance, and/or proteinuria
- Increased risk for superimposed preeclampsia, fetal growth
restriction and premature delivery
- Poor perinatal outcome.
 Diabetes Mellitus
- Maternal Complications -
• Retinopathy
- Retinopathy may worsen significantly during pregnancy
- Ophthalmologic examination should be performed especially in
patients with hypertensive disorders with a laser coagulation therapy if
needed

- Termination of pregnancy should only be considered in patients with

severe neovascularization unresponsive to laser therapy
 Care of DM during Pregnancy

• The goal of care is to avoid hyperglycemia

periconceptionally, during organogenesis, and during the
whole pregnancy.
• Preconceptional Care:
– Optimal medical care and education are recommended
before conception.
– Glycosylated hemoglobin measurement should be
within or near the upper limit of normal for a specific
laboratory.
– The most significant risk for malformations is with levels
exceeding 10 percent.
 First trimester

• Careful monitoring of glucose control is essential.

• Assess the extent of vascular complications of diabetes
• Establish gestational age.
• Multiple daily insulin injections and adjustment of
dietary intake is required to achieve maternal glycemic
control.
 DRUG THERAPY

• The degree of glycemic control desirable during pregnancy

can usually only be achieved with multiple daily insulin
injections .
• During the first trimester, insulin requirements are similar in
women with type 1 and type 2 diabetes.
• In the second half of pregnancy, insulin requirements
increase proportionately more in women with type 2 than
type 1 diabetes.
 Regimen

• Total daily insulin requirements vary during gestation.

• There is a rise in insulin requirements during late half of
pregnancy especially between weeks 28-32.
• Insulin requirements sometimes fall by 5% after 35 weeks of
gestation.
 Dose

• The average insulin requirement in pregnant women with

type 1 diabetes is:
- 0.7 units/kg in the first trimester,
- 0.8 U/kg for weeks 13 to 28,
- 0.9 U/kg for weeks 29 to 34, and
- 1.0 U/kg for weeks 35 to term.
 Oral anti-hyperglycemic agents
• Concerns are:
– Adequacy of glycemic control and
– Potential fetal and neonatal effects.
• Several studies:
– Have not found harmful effects from glyburide during pregnancy and
have reported effective glycemic control .
– Reported good outcomes with use of metformin in pre gestational
diabetics.
• Oral anti hyperglycemic agents are not as effective as insulin
in those with severe degrees of hyperglycemia.
• Not recommended by ACOG/ ADA.
 ASSESSING GLYCEMIC CONTROL

• Glucose monitoring
– It is recommended to have glucose monitoring before and
one hour after the first bite of meals, at bedtime, and
occasionally during the night if nocturnal hypoglycemia is
suspected .
• Urine ketones:
– Urinary ketones be measured when woman with type 1
diabetes are ill or when any blood glucose value is over
180 mg/dL.
 ASSESSING GLYCEMIC CONTROL

• Glycated hemoglobin:
– It provides an assessment of the degree of chronic
glycemic control.
– Can be determined monthly.
– Hemoglobin A1C values up to 1 percent above normal are
associated with rates of congenital anomalies and
miscarriage similar to the rates in the general population.
 TARGET BLOOD GLUCOSE VALUES

• The ACOG recommendation:

- Fasting glucose concentrations ≤95 mg/dL.
- Preprandial glucose concentrations no higher than 100 mg/dL.
- One-hr postprandial glucose concentrations no higher than 140
mg/dL
- Two-hr postprandial glucose concentrations no higher than 120
mg/dL.
- Glycated A1C ≤6 %
- During the night, glucose levels should not decrease below 60
mg/dL.
 Deleterious effects of strict glycemic
control
• There are two potential hazards from strict glycemic control:
hypoglycemia and worsening of diabetic retinopathy .
• Exceptionally strict glycemic control may impair fetal growth
and should be avoided.
Frequency of testing during pregnancy in women
with pregestatonal diabetes
 Second trimester

• Maternal serum alpha-fetoprotein determination at 16 to 20

weeks is used in association with targeted sonographic
examination at 18 to 20 weeks in an attempt to detect neural-
tube defects and other anomalies.
 Third trimester

• In the third trimester, diabetic gravida are seen as often as

every one to two weeks until 36 weeks of gestation, and then
weekly until delivery.
• During the third trimester, insulin resistance due to the
hormones produced by the placenta increases rapidly, and
changes in insulin dose are commonly required to maintain
euglycemia.
 Third trimester

• Obstetrical management during the third trimester

consists of:
– Reinforcement of good glycemic control,
– Electronic and sonographic fetal monitoring,
– Estimation of fetal size,
– Surveillance for pregnancy complications such as
preeclampsia or polyhydramnios.
 Assessment of fetal well-being

• The fetus of the diabetic mother is at risk for hypoxia so

antepartum fetal testing is recommended.
• The ACOG recommends antepartum fetal testing using fetal
movement counting, BPP ,NST, and/or CST with initiation of
testing generally at 32 to 34 weeks of gestation.
 Timing of delivery

• There is little benefit in continuing pregnancy beyond 39

weeks in women with diabetes, particularly those with a
favorable cervix.
• If glycemic control is suboptimal or there are other reasons
for concern, an acceptable approach is to induce labor at 38
weeks following an amniocentesis documenting fetal lung
maturity.
 Gestational Diabetes

• It is defined as carbohydrate intolerance of variable severity

with onset or first recognition during pregnancy.
• Gestational diabetes is type 2 diabetes unmasked or
discovered during pregnancy.
• Gestational diabetes mellitus (GDM) is to be expected in 5 to
8% of pregnant women.
 SIGNIFICANCE OF GDM IN
PREGNANCY
• Adverse outcomes include:
Preeclampsia, UTI , Hydramnios, macrosomia , Birth trauma
Operative delivery, Perinatal mortality,
Neonatal respiratory problems
metabolic complications (hypoglycemia, hyperbilirubinemia,
hypocalcaemia, erythremia.
• Unlike in women with overt diabetes, fetal anomalies are not increased .
• For the mother with gestational diabetes, there is a 10 % likelihood of
overt diabetes mellitus immediately after the index pregnancy.
• The likelihood of developing overt diabetes in the years following the
pregnancy is as high as 40 % within 20 years.
• After a pregnancy complicated by GDM, the recurrence risk in the next
pregnancy is about 50%.
 RISK FACTORS FOR GDM

• A family history of diabetes

• Body mass index over 30 kg/m2 or significant weight gain in
between pregnancies
• Age greater than 25 years
• Previous delivery of a baby greater than 4.1 kg
• Personal history of abnormal glucose tolerance
• Previous unexplained perinatal loss or birth of a malformed child
• Maternal birth weight greater than 4.1 kg or less than 2.7 kg
• Glycosuria at the first prenatal visit
• PCOS, Current use of glucocorticoids
• Hypertension
SCREENING VERSUS DIAGNOSTIC TESTING

• Screening is usually performed as a two-step process

where step one identifies individuals at increased risk for
the disease so that step two, diagnostic testing, can be
limited to these individuals.
– Two step approach - It is the most widely used approach for
identifying pregnant women with diabetes and is recommended
by ACOG .
– One step approach - It has been endorsed by the ADA , but not
by ACOG. Done by performing a 75 gram two hour oral GTT and
requiring only a single elevated value for diagnosis.
 Whom to screen

• Women with risk factors should be screened as soon as

feasible. If results of testing do not demonstrate diabetes,
these women should be retested between 24 and 28 weeks'
gestation.
• All women of ordinary or high risk should be screened
between 24 and 28 weeks' gestation.
• Universal screening appears to be the optimum approach
because 90 percent of pregnant women have risk factors for
glucose impairment during pregnancy.
 When to screen

• Universal screening is performed at 24 to 28 weeks of

gestation .
• Screening should be performed as early as the first prenatal
visit if there is a high degree of suspicion for undiagnosed
type 2 diabetes (e.g. obesity, personal history of gestational
diabetes, glycosuria, or strong family history of diabetes).
 How to screen
• There is no worldwide standard for screening and diagnosis of
diabetes during pregnancy.
• Two approaches:
– Two step approach
– One step approach.
 Two step approach

• This approach begins with a 50 gram oral glucose challenge

test for screening .
• The 50 gram oral glucose load is given without regard to the
time of the last meal and plasma glucose is measured one
hour later;
– A value ≥130 or ≥140 mg/dL is considered abnormal.
– The sensitivity of the 50 gram glucose test is improved if
the (≥130 mg/dL) plasma glucose threshold is used .
– Women with an abnormal value are then given a 100 gram
three hour oral GTT for definitive diagnosis.
 100 gram three hour OGTT
• The 100 gram three hour oral GTT is most commonly used
during pregnancy and is currently recommended by ACOG.
• 100 gram oral glucose load is given to a patient who is fasting.
• Two elevated glucose values are needed for a positive test.
100 gram OGTT
 One step approach
75 gram two hour OGTT
• The 75 gram two hour oral GTT as endorsed by the ADA is
more convenient, better tolerated, and more sensitive for
identifying the pregnancy at risk for adverse outcome than
the 100 gram three hour OGTT.
• Increased sensitivity is likely related to a lower threshold for a
positive test – only one elevated glucose value is needed and
the cut-offs are slightly lower.
 NEW TERMINOLOGY AND DIAGNOSTIC
CRITERIA
• The term “gestational diabetes” has been used to define
women with onset or first recognition of abnormal glucose
tolerance during pregnancy.

• Currently diabetes diagnosed during pregnancy is classified as

overt or gestational, ADA endorsed this recommendation.
 NEW TERMINOLOGY AND DIAGNOSTIC CRITERIA
Overt diabetes

 A diagnosis of overt diabetes can be made in women who

meet any of the following criteria at their initial prenatal visit:
• Fasting plasma glucose ≥126 mg/dL or
• A1C ≥6.5 percent using a standardized assay, or
• Random plasma glucose ≥200 mg/dL that is subsequently
confirmed by elevated fasting plasma glucose or A1C.
 NEW TERMINOLOGY AND DIAGNOSTIC CRITERIA
Gestational diabetes

 A diagnosis of gestational diabetes can be made in women

who meet either of the following criteria :
– Fasting plasma glucose ≥92 mg/ dL, but <126 mg/ dL at
any gestational age.
– At 24 to 28 weeks of gestation: 75 gram two hour oral
glucose tolerance test (GTT) with at least one abnormal
result:
- fasting plasma glucose ≥92 mg/dL , but <126 mg/dL
or
- one hour ≥180 mg/dL or
- two hour ≥153 mg/dL.
 MANAGEMENT OF GDM

• Appropriate therapy can decrease maternal and fetal

morbidity, particularly macrosomia.
• An effective treatment regimen consists of:
– Dietary therapy,
– Self blood glucose monitoring and
– Administration of insulin if target blood glucose
concentrations are not met with diet alone.
 Therapy of GDM
• Dietary therapy
- A good dietary counseling is mandatory.
- The diet should be adequate for the subjective and objective needs
of the pregnant woman, around 30 kcal/kg body weight per day
depending on the physical activity.
- Most programs suggest three meals and three snacks.
– Breakfast -10 % of total calories
– Lunch - 30 % of total calories
– Dinner -30 % of total calories
– Snacks - 30 % of total calories.
 Caloric requirements & distribution

• Caloric distribution:
– 33 to 40 % of calories….from carbohydrate.
– 20 % of calories……from protein.
– 40 % of calories….from fat, primarily unsaturated fats.
• Postprandial blood glucose concentrations are directly
dependent upon the carbohydrate content of a meal .
• The postprandial glucose rise, can be blunted if the diet is
carbohydrate restricted.
 Therapy of GDM
• Dietary therapy
Suited: Not suited:
Bread (except white bread), sweets, cake,chocolate,
cereals, honey, marmelades,
potatoes, rice, noodles, juices, lemonades or soft drinks,
salads, vegetables, figs, dates, raisins,
fruits, dried fruits
dairy products,
spices, vinegar, mustard, oil,
eggs, meat, fish,
coffee, tea, mineral-water
 Therapy of GDM

• Physical activity

- Physical activity normalizes blood glucose levels by direct energy

consumption and by increasing cellular sensitivity to insulin.
- Most helpful is long-term aerobic work-out like walking.

- Obstetrical contraindications should be kept in mind.

 Drug treatment
• Insulin therapy is usually recommended when standard
dietary management does not consistently maintain the
fasting plasma glucose at < 95 mg/dL or the 2-hour
postprandial plasma glucose < 120 mg/dL (ACOG).
 Obstetrical Monitoring

• The mother must be checked for signs of urinary tract

infections, vaginal infections, hypertension, and preeclampsia.
• Women with class A1 GDM are not at increased risk of
stillbirth.
– Antepartum fetal surveillance is not required.
• Women with class A2 GDM are managed the same way as
women with pregestational diabetes.
– Antepartum fetal surveillance is initiated at about 32
weeks of gestation.
 Timing of delivery

• Women with gestational diabetes who do not require insulin

seldom require early delivery.
• In class A1 GDM elective induction is recommended at 41
weeks of gestation.
• In class A2 GDM induction of labor is recommended at 39
weeks of gestation.
• If there is concomitant medical condition or glycemic control
is suboptimal induction of labor is recommended at 38 weeks
of gestation after confirmation of fetal lung maturity.
• Cesarean delivery should be considered in women with a
sonographically EFW >= 4500 g.
 Labor and delivery

• Maternal hyperglycemia should be avoided during labor

to reduce the risk of fetal acidosis and neonatal
hypoglycemia.
• Insulin requirements usually decrease during labor.
• Women with GDM who used insulin to maintain
euglycemia may need an insulin infusion during labor
and delivery to maintain euglycemia after checking blood
glucose measurements every 1-2 hours during labor.
 Postpartum Evaluation & follow up

• Nearly all women (≥90 percent) with GDM are normoglycemic

after delivery.
• Some women with GDM might have undiagnosed type 2 DM,
so check blood glucose concentrations for 24 to 48 hours
after delivery.
• Women diagnosed with gestational diabetes should undergo
evaluation with a 75-g oral glucose tolerance test at 6 to 12
weeks postpartum and other intervals thereafter.