Diabetes in pregnancy

Objectives
 Sources Of the lecture
 ADA 2019

 ACOG 2018

 NICE guidelines 2015

 JOHN HOPKINS TEXT BOOK

 NMS Obstetrics and Gynecology, 6th

Edition
Physiologic changes in pregnancy
 Glucose is central to energy metabolism and is the

preferred energy source for most cells.

 It comes from three sources :-

• Ingested food

• Glycogenolysis

• Gluconeogenesis
Maternal energy metabolism and the role of
insulin
Effect of pregnancy on glucose metabolism
 Glucose metabolism is altered during pregnancy:

a. Fasting levels are decreased

(10–15% lower than in the non pregnant state)

b. Postprandial levels are increased

 Increased insulin secretion occurs as a result of

pancreatic beta cell hyperplasia from the increased

levels of estrogen and progesterone.
 Insulin antagonism results from the increase

in human Human Placental Lactogen, Cortisol

and glucagon.(Pregnancy is a state of
physiological insulin resistance, specially 3rd
trimester )
 Increased insulin degradation by placental

insulinase occurs.
 There is decrease in renal tubular

threshold for glucose, so most pregnant

women will have glycosuria at some time
 In normal pregnancy, starvation results in

early breakdown of triglycerides, resulting

in the liberation of fatty acids and ketone
bodies.
(“accelerated starvation of pregnancy.” )
 Classification of DM in Pregnancy

Pre-existing Gestational
diabetes diabetes

True
Pre-exisitng
IDDM gestational
NIDDM diabetes
diabetes
NID
White Classification System for Diabetes
Mellitus
 Definition and Prevalence

 Gestational diabetes mellitus is a condition

in which carbohydrate intolerance
develops during pregnancy.
 7% of pregnancies were complicated by any

type of diabetes and that approximately 86%

of these cases represented women with
GDM

(ACOG 2018)
 In England and Wales up to 5% of
these women have either pre-existing
diabetes or gestational diabetes.
 It is estimated that approximately 87.5%

have gestational diabetes 7.5% have type

1 diabetes and the remaining 5% have
type 2 diabetes. (NICE 2015)
 In type I , the baby of affected mother has

2% risk of developing DM, if the father is

affected, the risk is 8%, and if both the risk
rises to 30%
 In type II; the risk to offspring is higher
than type I. If any one of the parents is
affected, the risk is 15%, if both are affected,
the risk is 75%
 The risk of developing GDM in

subsequent pregnancies is high, with

recurrence rate between 30-84%.
 Women with GDM who required insulin

therapy, have a recurrence rate of 75%..

 SCREENING & DIAGNOSIS
1NICE recommends screening for
all women with the following risk
factors:
* BMI>30
* 1st degree relative with DM
* Previous macrosomic baby ≥4.5 kg.
* Previous GDM.
* Ethnic origin:
a- South Asian b- Black
Caribbean c- Middle Eastern
( Arab).
2-According to (ACOG2018) Consider testing in all
women who are overweight or obese and have one
or more of the following additional risk factors:
• Physical inactivity

• First-degree relative with diabetes

• High-risk race or ethnicity (eg, African

American, Latino, Native American, Asian
American, Pacific Islander)
• Have previously given birth to an infant
weighing 4,000g or more .
• Previous gestational diabetes mellitus

• Hypertension

• High-density lipoprotein level less than 35 mg/dL

(0.90 mmol/L), a triglyceride level greater
than 250 mg/dL (2.82 mmol/L)
• Women with polycystic ovarian syndrome

• A1C greater than or equal to 5.7%, impaired

glucose tolerance, or impaired fasting glucose
on previous testing
Time :
⚫ Screening is done between 24-28 weeks.

⚫ NICE recommends that women with

previous GDM should be offered early

screening as soon as possible after booking
(whether in the first or second trimester).

If normal, to be repeated at 28 weeks

Screening tests:
1) 1 step OGTT:

a.It is used in most of the world except

North America.

b. It involves the ingestion of 75 gm. glucose.

c.Fasting and 2 hrs. blood glucose level

are measured.
 Diagnose gestational diabetes if the
woman has either:
O a fasting plasma glucose level of
5.6mmol/litre or above or

O a 2-hour plasma glucose level of

7.8mmol/litre or above.
5.6mmol/litre = 100.8 mg/dl

- 7.8mmol/litre = 140.4 mg/dl

[NICE 2015]
2) 2-step OGTT:
a. Commonly used in North America.

b.A 50 g glucose tolerance test is used

to screen women. This is followed in
screen positive women ( 1hr level >140
mg/dl) with full 3hr 100g oral glucose
tolerance test
 The test is considered abnormal and diagnostic
for GDM if any two or more plasma glucose
values meet or exceed the following thresholds :
 Maternal complications
 Increase insulin requirements:
1Rapid increase in requirements
occurs, specially between 28-32 weeks.

2The maximum dose at term usually

reaches at least 2 –folds the pre-pregnancy
does.
 Nephropathy:
- If renal assessment has not been undertaken
in the preceding 3 months in women with pre
existing diabetes, arrange it at the first contact
in pregnancy

O If the serum creatinine is abnormal (120

micromol/litre or more), the urinary
albumin:creatinine ratio is greater than 30
mg/mmol or total protein excretion exceeds 2
g/day, referral to a nephrologist should be
considered ( NICE 2008, amended 2015 )
 Retinopathy

• There is 2 fold risk of progression

of retinopathy during pregnancy.
• The risk is higher for type I than type II DM

• Diabetic retinopathy should not

be
considered a contraindication to vaginal birth.
 Hypoglycemia:

• More common in pregnancy.

• Most maternal deaths due to diabetes in

the UK are due to hypoglycemia !!!

 Diabetic ketoacidosis (DKA):
• It is associated with poor maternal and

fetal outcome.
• Risk increases in the presence of emesis,

infection, tocolysis using

β sympathomimetic and
corticosteroid therapy
 Preeclampsia:
• There is an increased risk, and it increase more if
there is pre-existing HTN or renal disease.

• The risk is related to glycemic control

at
conception and in the first half of pregnancy.

• Every 1% increase in HbA1c in the 1st trimester,

increase the risk by 60%, and every 1%
decrease, decrease the risk by 40%.
 Preterm Labor

 Polyhydramnios

 Increased risk of infection during

pregnancy. Including UT,
respiratory,
endometrial, vaginal and wound infection.
 Increased risk of cesarean delivery (25%
of women with GDM who require medication and
17% of women with diet-controlled GDM
underwent cesarean delivery versus 9.5% of
controls) (ACOG 2018)
Fetal& neonatal complications
 Congenital anomalies:

O Reports estimate an incidence of 6-9%.

O The incidence is linked to periconceptional

diabetic control and correlates with the level of

HbA1C

O Advise women with diabetes who are planning to

become pregnant to aim to keep their HbA1c

level below 48 mmol/mol (6.5%) .

[NICE 2015
– ADA 2019]
O Strongly advise women with diabetes whose
HbA1c level is above 86 mmol/mol (10%)
not to get pregnant because of the
associated risks of both minor and major
anomalies are increased .
Common anomalies:
Cardiac…the most common , increased five
fold in fetuses of diabetic pt. (
VSD,ASD,TGV… )
- CNS. A 10-fold increase is seen in the incidence
of CNS malformations,( anencephaly,
holoprosencephaly, open spina bifida ,
microcephaly, encephalocele, and
meningomyelocele

- GI. Malformations of the GI system are also

found
)tracheoesophageal fistula, bowel atresia, and
imperforate anus )

- Genitourinary (GU) System. GU anomalies (

absent kidneys (Potter's syndrome),
polycystic kidneys, and double ureters.)
 Spontaneous miscarriage
There is an increased risk of spontaneous abortion
associated with increased first-trimester HbA1c values
 Sudden unexplained IUFD

• The risk is highest after 36 weeks.

• Multifactorial causes including: Chronic hypoxia, fetal

academia and maternal DKA.

• Maternal DKA is associated with high (30-50%) fetal

mortality rate.
⚫ Birth weight:
The macrosomic baby of the diabetic mother is fatty and
plethoric, with all organs, with the exception of the
brain, being enlarged due to an increase in cytoplasmic
mass.

It is partially explained by Pedersen hypothesis, elevated

maternal levels of glucose placenta,
resulting and cross the in Fetal
hyperinsulinemia
fetal actshyperinsulinemia.
as an anabolic stimulus, leading
to enhanced accretion of fat, bone and muscle mass
 Respiratory dysfunction:
• The incidence of respiratory distress syndrome (RDS)
among IDM is 5–6-fold higher than the incidence
among infants of non-diabetic women.
• Insulin and androgens inhibit surfactant secretion in
mammals. This explains the in the
difference incidence of RDS between both
sexes.
• The problem
Neonatal is self-limiting and usually
hypoglycemia:
resolves within 48 hours of birth.
 Polycythemia:

• Insulin directly stimulates

erythroid progenitors in the marrow to make
more red cells. Elevated levels of insulin also
stimulate erythropoiesis indirectly by
stimulating elevated levels of erythropoietin
• Mild polycythemia may contribute to
the increased incidence of hyperbilirubinemia
and jaundice seen in IDM.
 Hypocalcemia and hypomagnesemia:
are common among IDM, each approximately 20–30%, and
usually asymptomatic. these conditions should be considered if
a baby remains unusually “jittery” despite normal glucose levels.

 Hypertrophic cardiomyopathy:

Rare in absence of macrosomia

Long-term neurodevelopmental
outcome: ketoacidosis in diabetic women in late
pregnancy is associated with adverse
neurodevelopmental
consequences for their offspring.
 Management

OPrepregnancy counseling

OMedical management

OObstetric management
 Prepregnancy counseling
 Optimize glycemic control.

 Women with BMI> 27 should be advised regarding

weight loss..
 Strongly advise women with diabetes whose

HbA1c level is above 86 mmol/mol (10%) not to

get pregnant because of the associated risks
 Folic acid 5 mg

 Initial evaluation ( multidisciplinary )

Components of diabetes evaluation
 Medical management
 Glycemic control:
O The goal is to achieve
maternal normoglycemia.

O Outcomes correlates better with

postprandial than preprandial glucose
levels
O Advise pregnant women with type 1 / type

2 diabetes or gestational diabetes who are

on a multiple daily insulin injection to test
their (fasting, pre-meal, 1-hour post-meal
and bedtime) blood glucose levels daily
during pregnancy

[NICE 2015]
O Advise pregnant women with type 2 diabetes or
gestational diabetes to test their fasting and 1-
hour post-meal blood glucose levels daily during
pregnancy if they are:
- on diet and exercise therapy or
-taking oral therapy (with or without diet and
exercise therapy) or single-dose intermediate-
acting or long-acting insulin.

[NICE 2015]
O Measure HbA1c levels in all pregnant women
with pre-existing diabetes at the booking
appointment to determine the level of risk for
the pregnancy.

O Measure HbA1c levels in all women with

gestational diabetes at the time of diagnosis to
identify those who may have pre-existing type 2
diabetes.

[NICE

2015]
O The general recommendation is for daily
glucose monitoring four times a day, once after
fasting and again after each meal.
O The 1-hour postprandial measurement was
associated with better glycemic control, a lower
incidence of LGA infants, and lower rates of
cesarean delivery for cephalopelvic
disproportion
(ACOG 2018)
O Goal Glucose Levels for Adequate Glycemic
Control
• fasting: 5.3 mmol/litre (
95mg/dl ) and
• 1 hour after meals: 7.8mmol/litre (140mg/dl ) or
• 2 hours after meals: 6.4mmol/litre. (115mg/dl )
[NICE
2015]
• (The ADA & ACOG) recommend that fasting or

preprandial blood glucose values be below (95

mg/dL) and postprandial blood glucose values be
below (140 mg/dL) at 1 hour or (120 mg/dL) at 2
hours
 Diet:

O An appropriate daily distribution of dietary

calories is approximately 33–40% of total
calories from carbohydrate, 20% from protein
and the 40% from fat.

O 80-90% of GDM can achieve glycemic control

with diet alone.

(ACOG 2018)
 Exercise
O women with GDM should aim for 30 minutes of

moderate-intensity aerobic exercise at least 5 days

a week or a minimum of 150 minutes per week

O Simple exercise such as walking for 10–15 minutes

after each meal can lead to improved glycemic

control and is commonly recommended

(ACOG
2018)
 Oral hypoglycemic agents

Metformin is a biguanide that inhibits hepatic

gluconeogenesis and glucose absorption and
stimulates glucose uptake in peripheral tissues.

O Metformin crosses the placenta with levels

that can be as high as maternal
concentrations.

O The long-term metabolic influence on the

offspring is unknown
O Metformin generally is not used in patients with

chronic renal disease, creatinine often Is

checked at baseline

O Metformin may slightly increase the risk of

prematurity.

O The most common adverse effects of

metformin are abdominal pain and diarrhea,
which are minimized by slowly increasing the
dosage
O In women who decline insulin therapy or who
the obstetricians believe will be unable to
safely administer insulin, or for women who
cannot afford insulin, metformin is a
reasonable alternative choice.

O The dosage for metformin usually starts at 500

mg nightly for 1 week at initiation, then
increases to 500 mg twice daily
The maximum dose is usually 2,500–3,000 mg
per day in two to three divided doses

(ADA 2019)
o Glyburide

• is a sulfonylurea that binds to pancreatic beta-

cell adenosine triphosphate potassium channel

receptors to increase insulin secretion and insulin
sensitivity of peripheral tissues
• The common dosage of glyburide is 2.5–20 mg

daily in divided doses.

• The evidence indicates that glyburide
treatment should not be recommended as a
first-choice pharmacologic treatment
because, in most studies, it does not yield
equivalent outcomes to insulin or metformin.
• Glyburide was associated with a higher rate
of neonatal hypoglycemia and macrosomia
than insulin or metformin. (ADA 2019)
 Insulin

O Insulin is the preferred agent for management

of both type 1 diabetes and type 2 diabetes in

pregnancy because it does not cross the
placenta and because oral agents are generally
insufficient to overcome the insulin resistance
in type 2 diabetes and are ineffective in type 1
diabetes . (ADA 2019)
O The starting total dosage is 0.7–1.0 units/kg
daily. This dosage should be divided with a
regimen of multiple injections using long-
acting or intermediate acting insulin in
combination with short-acting insulin
O Insulin lispro and insulin aspart should be
used preferentially over regular insulin
because both have a more rapid onset of
action, enabling the patient to administer
her insulin right at the time of a meal rather
than 10–15 minutes before an anticipated
meal. This provides better glycemic control
and helps avoid hypoglycemic episodes from
errors in timing (ADA ,ACOG 2018)
O A systematic review and meta-analysis of
randomized trials of standard versus CSII
pump therapy during pregnancy was unable
to identify any maternal or fetal benefits to
CSII pump therapy.
 Obstetric management
 Booking appointment
• Discuss information, education and advice about how

diabetes will affect the pregnancy

• Offer retinal & renal assessment for women with pre-

existing diabetes unless the woman has been assessed

in the last 3 months.
• Measure HbA1c levels for women with pre-existing

diabetes to determine the level of risk for the pregnancy.

• Offer self-monitoring of blood glucose or a 75 g 2-

hour OGTT as soon as possible for women with a

history of gestational diabetes who book in the first
trimester.
• Confirm viability of pregnancy and gestational age at
7–
9 weeks.
• Women with type 1 or type 2 diabetes should be

prescribed low-dose aspirin 60–150mg/day (usual

dose 81 mg/day) from the end of the first trimester until
the baby is born in order to lower the risk of
preeclampsia.

(ADA 2019)
 16 weeks:

• Offer retinal assessment at 16–20

weeks to women with pre-existing
diabetes if diabetic retinopathy was
present at their first antenatal clinic visit.
 20 weeks
• Offer an ultrasound scan for detecting fetal
structural abnormalities, including examination of the fetal
heart
 28 weeks
• Offer ultrasound monitoring of fetal growth and amniotic
fluid volume.
• Offer retinal assessment to all women with pre-existing
diabetes.
• Women diagnosed with gestational diabetes as a result
of routine antenatal testing at 24–28 weeks enter the care
pathway.
 32 weeks
• Offer ultrasound monitoring of fetal growth and amniotic
fluid volume.
36 weeks
• Offer ultrasound monitoring of fetal growth and
amniotic fluid volume.
• Provide information and advice about: timing, mode

and management of birth analgesia and anaesthesia

changes to blood glucose-lowering therapy during and
after birth
• care of the baby after birth

• initiation of breastfeeding and the effect of

breastfeeding on blood glucose control
• contraception and follow-up.
 37+0 weeks to 38+6 weeks

• Offer induction of labour, or caesarean

section if indicated, to women with type 1 or type 2
diabetes; otherwise await spontaneous labour.

 38 weeks

• Offer tests of fetal wellbeing.

 39 weeks

• Offer tests of fetal wellbeing.

• Advise women with uncomplicated gestational diabetes
to give birth no later than 40+6 weeks.
(NICE 2015)
 Intrapartum care:
• Advise women with gestational diabetes to give birth no
later than 40+6 weeks, and offer elective birth (by
induction of labour, or by caesarean section if indicated) to
women who have not given birth by this time.
• Advise pregnant women with type 1 or type 2 diabetes
and no other complications to have an elective birth by
induction of labour, or by elective caesarean section if
indicated, between 37+0 weeks and 38+6 weeks of pregnancy.
• Consider elective birth 34- 37 weeks for women with type 1
or type2 diabetes if there are metabolic or any other maternal
or fetal complications.
[NICE
2015]
• Continues I.V infusion of short-acting insulin and
dextrose administered via separate access. This helps
good control of normoglycemia.
• The usual insulin dose range is 2-6 units and dextrose

75-125 ml/hr. The target is to keep maternal blood

glucose between 4-7 mmol/l (72-126 mg/dl).
• Capillary blood glucose is monitored hourly.

• Immediately post partum, maternal insulin requirements

drop rapidly
 Postnatal care

• Women with pre-existing diabetes can be shifted to

pre-pregnancy dosing, once eating normally.

• For women who were diagnosed with gestational

diabetes and whose blood glucose levels returned

to normal after the birth:
 Offer lifestyle advice (including weight control, diet

and exercise).
 Offer a fasting plasma glucose test 6–13 weeks after

the birth to exclude diabetes

 offer a fasting plasma glucose test, or an HbA1c

test if a fasting plasma glucose test is not

possible, after 13 week
 Offer an annual HbA1c test to women who were

diagnosed with gestational diabetes who have a

negative postnatal test for diabetes.

[NICE
2015]
 Breastfeeding

 Breastfeeding increases frequency

hypoglycemia the in of
diabetics. dependent
 Women should beinsulin
advised to take a snack
before or during breast feeding.
 Contraception

 Natural family planning and barrier

methods are safe for all but their effective use

requires considerable motivation
 Both copper and levonorgestrel IUD

seem equally safe and effective in diabetic and

nondiabetic women and they should be offered as
a reasonable option
 hormonal contraception

• ACOG recommends that be reserved for diabetic women

who are otherwise healthy, young (under age 35),

nonsmokers, without hypertension, retinopathy,
nephropathy or other evidence of vascular disease

 contraceptive ring or patch

• There is insufficient information to recommend their use

in diabetic women.