This document discusses diabetes in pregnancy. It describes the physiological changes in pregnancy that can increase insulin resistance and glucose levels. It also discusses the effects of pre-existing diabetes on pregnancy, including increased insulin needs and risks of complications for both mother and fetus like hypoglycemia, macrosomia, and birth defects. The document provides guidelines for managing diabetes before and during pregnancy to optimize health and limit risks through measures like glycemic control, nutrition, medication, and screening for diabetes-related complications.

1. DIABETES
IN
PREGNANCY
Prof.
Aboubakr
Elnashar
Benha
ubiversity
Hospital,
Egypt
elnashar53@hotmail.com
PHYSIOLOGICAL
CHANGES
1.
Insulin
resistance
&
relative
glucose
intolerance.
▪
Increasing
after
the
first
trimester
▪
Due
to
diabetogenic(anti-insulin)hormones
secreted
by
placenta
▪
human
placental
lactogen
▪
Cortisol
▪
Glucagon
▪
oestrogen
▪
progesterone
▪
Insulin
requirements
increase
throughout,
maximal
at
term.

2. 2.
The
renal
tubular
threshold
for
glucose
falls:
▪
Glycosuria
▪
Glycosuria
is
not
a
reliable
diagnostic
tool
for
impaired
glucose
tolerance
or
diabetes
in
pregnancy.
3.
Starvation
results
in
early
breakdown
of
triglyceride:
liberation
of
fatty
acids&ketone
bodies:
increased
risk
of
ketoacidosis.
▪
This
is
most
marked
in
the
third
trimester.

3. PRE-EXISTING
DIABETES
MELLITUS
1.
PREVALENCE
▪
1–2%
of
pregnancies.
▪
In
the
UK,
▪
type
1
is
about
0.5%
▪
type
2
about
3%–4%
(lower
in
women
of
childbearing
age,
but
higher
in
Afro-
Caribbean
and
10%
in
Asian
ethnicities).
▪
pre-existing
diabetes
in
pregnancy
0.4%
(0.27%
type
1
and
0.1%
type
2).
2.
DIAGNOSIS
OF
DM
(IN
NON-PREGNANT
WOMEN)
▪
One
of
the
following
criteria
must
be
confirmed
by
repeated
testing
on
a
subsequent
day
unless
the
patient
is
symptomatic
(i.e.,
polyuria,
polydipsia,
unexplained
weight
loss)
in
which
case
a
single
abnormal
value
suffices:
▪
R
venous
plasma
glucose
≥11.1
mmol/L
(200mg/dl)
▪
F
plasma
glucose
≥7.0
mmol/L
(126mg/dl)
(whole
blood
≥6.1
mmol/L)
(110mg/dl)
▪
2-hour
plasma
glucose
≥11.1
mmol/L
(200mg/dl).
2
hours
after
75
g
OGTT
▪
Type
2
diabetes
diagnosed
using
HbA1C
threshold
of
48
mmol/L
(6.5%).
▪
Diagnosis
requires
a
second
value
above
48
mmol/L.
▪
42–47
mmol/L
(6.0%–6.4%)
are
deemed
at
high
risk
of
diabetes&should
have
lifestyle
advice&annual
monitoring.

4. Diagnosis
of
impaired
glucose
tolerance
▪
IGT
is
a
stage
of
impaired
glucose
regulation
▪
F
plasma
glucose
<7.0
mmol/L
(126mg/dl)
and
▪
OGTT
2-hour
value
≥7.8
mmol/L
(140mg/dl)
but
<11.1
mmol/L.(200mg/dl)
Impaired
fasting
glucose
▪
F
glucose
≥6.1
mmol/L(110mg/dl)
but
<7.0
mmol/L.(126mg/dl)
3.
EFFECT
OF
PREGNANCY
ON
DIABETES
1.
Insulin
requirements
▪
{normal
pregnancy
is
associated
with
an
increase
in
insulin
production
&
insulin
resistance}
▪
Type
1
diabetes
require
increasing
doses
of
insulin
as
pregnancy
progresses.
▪
Maximum
requirements
at
term
usually
reach
at
least
2
fold
pre-pregnancy
doses.
▪
Type
2
diabetes
often
need
the
addition
of
insulin
to
their
therapy
or
increasing
doses
of
insulin.
▪
Rapid
increases
in
insulin
requirements
between
28&
32
w,
when
the
fetus
is
growing
rapidly.

5. 2.
Hypoglycaemia
▪
More
common
in
pregnancy
{intensified
diabetic
control
‘hypoglycaemia
unawareness}’.
▪
Many
maternal
deaths
caused
by
diabetes
are
due
to
hypoglycaemia.
▪
For
every
1%
fall
in
HbA1C,
there
is
a
33%
increase
in
hypoglycaemic
attacks.
3.
Ketoacidosis:
▪Rare
▪may
be
associated
with
▪Hyperemesis
▪Infection
▪Tocolysis
(
β
sympathomimetics),
or
▪Steroid
therapy.

6. 4.
Retinopathy:
▪Two-fold
increased
risk
of
development
or
progression
of
existing
disease.
▪Rapid
improvement
in
glycaemic
control:
increased
retinal
blood
flow,
which
can
cause
retinopathy.
▪All
diabetic
women
should
have
assessment
for
retinopathy
in
pregnancy,
and
proliferative
retinopathy
requires
treatment.
▪Early
changes
usually
revert
after
delivery.
5.
Nephropathy:
▪5–10%.
▪Renal
function
&
proteinuria
may
worsen
during
pregnancy.
▪usually
temporary.
▪increased
risk
of
▪pre-eclampsia
▪IUGR
▪
increased
surveillance
is
required.

7. 6.
Ischaemic
heart
disease:
▪{Pregnancy
increases
cardiac
workload}.
▪Women
with
symptoms
should
be
assessed
by
a
cardiologist
before
conception.
7.
Women
with
autonomic
neuropathy
and
gastric
paresis
often
experience
deterioration
of
their
symptoms
in
pregnancy.
4.
EFFECT
OF
DIABETES
ON
PREGNANCY
I.
Maternal
hyperglycaemia:
fetal
hyperglycaemia.
II.
Fetal
hyperglycaemia:
hyperinsulinaemia
(through
β
–cell
hyperplasia
in
fetal
pancreatic
cells).
Insulin
acts
as
a
growth
promoter:
•
macrosomia
•
organomegaly
•
increase
erythropoiesis
•
fetal
polyuria
(polyhydramnios).

8. III.
Neonatal
hypoglycaemia:
{removal
of
maternal
glucose
supply
at
birth
from
a
hyperinsulinaemic
fetus}.
Respiratory
distress
syndrome:
▪more
common
{surfactant
deficiency
occurring
through
reduced
production
of
pulmonary
phospholipids}.

9. 5.
COMPLICATIONS
OF
DIABETES
IN
PREGNANCY
I.
Maternal
•Infections:
UTI.,
recurrent
vulvovaginal
candidiasis,
respiratory,
endometrial,
wound
infections
•
Pregnancy-induced
hypertension/pre-eclampsia.
•
Retinopathy
(15%).
•
Nephropathy.
•
Cardiac
disease.
▪Obstructed
labour.
•
Operative
deliveries:
CS
&
assisted
vaginal
deliveries.
II.
Fetal
•
Miscarriage*
•
Congenital
abnormalities:
In
diabetics
with
poor
control
▪
The
specific:
sacral
agenesis,
but
this
is
very
rare
▪
More
common:
congenital
heart
defects,
skeletal
abnormalities,
NTD.
•
Preterm
labour.
•
Polyhydramnios
(25%).
•
Macrosomia
(25–40%).
•
IUGR.
•
Unexplained
IUD.

10. ▪
Congenital
abnormalities.
▪
Incidence:
4%
(double
background)
▪
3fold
increase
of
NTD
and
congenital
heart
disease.
▪
Risk:
directly
related
to
▪
glycaemic
control
around
the
time
of
conception
▪
HbA1C.
▪
<8%:
risk
of
5%
▪
>10%:
risk
is
as
high
as
25%.
▪
Normal:
risk
is
eliminated
▪
Recommendation
at
the
time
of
conception.
▪
HbA1C
should
be
<7%
(USA)
<6.1%in
(UK)
▪
Macrosomia
▪
B
wt>4.5
kg
or
>90th
percentile
for
g
age.
▪
Insulin
is
an
anabolic,
growth-promoting
hormon
▪
baby
is
fat
and
plethoric,
with
all
organs
enlarged
particularly
the
liver
▪
More
common
with
poor
diabetic
control,
but
may
also
occur
in
cases
of
excellent
control.
▪
incidence
increases
significantly
when
mean
maternal
blood
glucose
>7.2
mmol/L(130mg/dl)
▪
incidence
of
b
wt
>4
kg
was
21%
▪
incidence
of
shoulder
dystocia
was
8%.
▪
Often
associated
with
polyhydramnios
{fetal
polyuria}:
preterm
PROM
and
cord
prolapse.
▪
increases
the
risk
of
traumatic
delivery,
particularly
shoulder
dystocia.

11. ▪
Sudden
unexplained
IUD
▪
inversely
related
to
the
degree
of
diabetic
control
▪
highest
after
36w.
▪
Chronic
hypoxia
(more
common
in
macrosomic
babies
in
the
presence
of
hyperglycaemia
&
lactic
acidosis.
▪
Not
predicted
from
CTG,
Doppler
velocimetry
or
FBP.
▪
Maternal
hyperglycaemia,
and
particularly
ketoacidosis
▪
detrimental
to
the
fetus,
high
(10%–25%)
fetal
mortality
▪
In
contrast,
maternal
hypoglycaemia
is
well
tolerated
by
fetus.
III.
Neonatal
•
Polycythaemia.
•
Jaundice.
•
Hypoglycaemia.
•
Hypocalcaemia.
•
Hypomagnesaemia.
•
Hypothermia.
•
Cardiomegaly.
•
Birth
trauma:
shoulder
dystocia,
fractures,
Erb’s
palsy,
asphyxia.
•
Respiratory
distress
syndrome.

12. ▪
Fetal
hyperinsulinaemia
▪
may
lead
to
chronic
fetal
hypoxia:
stimulates
extramedullary
haemopoiesis,
fetal
polycythaemia
and
neonatal
jaundice.
▪
In
the
presence
of
fetal
hyperinsulinaemia,
when
the
cord
is
clamped,
the
neonate
is
‘cut
off’
from
its
supply
of
glucose
from
the
mother
and
is
at
risk
of
neonatal
hypoglycaemia.
▪
Perinatal
and
neonatal
mortality
rates
▪
can
be
increased
five-
to
tenfold
in
babies
▪
relate
to
HbA1C
at
conception
and
in
early
pregnancy.
▪
perinatal
mortality
rate
for
both
type
1
and
type
2
diabetes
was
about
3%.

13. 7.
MANAGEMENT
I.
Prepregnancy
care
▪
This
is
one
of
the
most
important
aspects
1.
Achievement
of
optimal
control:
▪
FBS:
between
63-106mg/dl
▪
1h
post-prandial
<140
mg/dl
(increased
risk
of
miscarriage
and
congenital
abnormalities
with
poor
control).
2
.
Assessment
of
severity
of
diabetes:
check
for
▪Hypertension
▪Nephropathy
▪U&E
▪Urinalysis
▪urinary
protein:
creatinine
ratio
▪24h
urine
for
protein.
Proteinuria
should
be
documented
and
quantified
prior
to
pregnancy
with
an
ACR
or
PCR.
▪Creatinine
clearance
{PET
is
increased
in
the
presence
of
microalbuminuria
(30–
300
mg/day)
although
to
a
lesser
degree
than
in
those
with
frank
nephropathy
(>300
mg/day).

14. ▪Retinopathy
▪fundoscopy,
ophthalmology
assessment.
▪If
necessary,
proliferative
retinopathy
may
be
treated
with
photocoagulation
prior
to
conception
▪Neuropathy
▪clinical
assessment
▪Cardiac
disease.
3.
Education
▪Good
control:
▪Decreased
F
congenital
abnormalities&
preeclampsia
▪improved
pregnancy
outcome
▪Effects
of
hyperglycaemia
on
fetus
▪Need
for
tight
control
▪To
inform
doctor
as
soon
as
pregnancy
confirmed
▪Some
drugs
may
need
stopping
(ACEIs).
4.
General
health:
▪stop
smoking
▪optimize
weight
(aim
for
a
normal
BMI),

15. 6.
Medications
▪
Folic
acid:
{Increased
risk
of
NTD}:
1mg
folic
acid.
▪
Rubella
status:
offer
vaccination
if
not
rubella
immune.
▪
Contraception:
until
good
control
achieved
▪
Unplanned
pregnancy
is
a
risk
factor
for
LFGA
▪
Contraindications
to
pregnancy
▪
ischaemic
heart
disease
▪
untreated
proliferative
retinopathy,
▪
severe
gastroparesis
▪
severe
renal
impairment
(CKD
4/5;
creatinine
>250
μmol/L).
II.
Antenatal
care
▪Multidisciplinary
team
with
a
diabetologist.
1.
Medical
management
1.
Control
of
DM
▪
Diet:
▪
Strict
adherence
to
a
low-sugar,
low-fat,
high-fibre
diet
▪
low
glycaemic
index.
▪
Starvation
and
severe
calorie
restriction
should
be
avoided
because
of
the
risk
of
ketoacidosis
▪
HbA1c
every
month:
▪
reflects
control
over
the
preceding
2mths.
.

16. ▪
Home
blood
glucose
monitoring
(HBGM)
▪
using
▪
glucose
oxidase
strips
and
glucose
meters
or
▪
ideally
a
continuous
glucose
monitoring
sensor
(CGMS)
(such
as
the
Freestyle
Libre®).
▪
spend
more
time
within
target
glucose
levels.
▪
lower
rate
of
LGA
babies,
and
improved
neonatal
outcome
▪Test
blood
glucose
levels
at
least
4
times/d
▪usually
before
meals
but
post-meal
glucose
may
give
tighter
control
▪before
going
to
bed
at
night.
▪
Target
capillary
blood
glucose
▪
Fasting:
3.5–5.3
mmol/L
(63-95mg/dl)
▪
1
H
PP:
<7.8
mmol/L
(140mg/dl)
(the
same
for
types
1,
2
and
gestational
diabetes).
▪
Outcomes
such
as
b
wt
&
neonatal
hypoglycaemia
correlate
better
with
postprandial
than
with
preprandial
glucose
levels.
▪
Using
postprandial
targets
also
leads
to
better
improvements
in
maternal
HbA1C
levels.

17. ▪
Management
of
type
1
diabetes
▪
Increasing
doses
of
insulin
throughout
pregnancy,
although
insulin
requirements
may
fall
or
be
variable
in
1
st
trimester.
▪
The
inevitable
result
of
tighter
control
is
an
increased
risk
of
hypoglycaemic
attacks.
▪
Women
should
be
warned
about
risks
of
hypoglycaemia&
unawareness
of
hypoglycaemia
particularly
in
1st
trimester.
▪
usually
require
a
‘snack’
mid-morning,
mid-afternoon,
and
before
retiring
at
night.
▪
Women
should
be
provided
with
concentrated
glucose
solution
for
use
in
the
event
of
hypoglycaemia.
▪
Relatives
or
partners
may
be
taught
how
to
administer
IM
glucagon
injections
to
avert
profound
hypoglycaemia
in
situations
where
the
woman
is
unable
or
unwilling
to
eat
or
drink.
The
woman
should
be
advised
that
glucagon
provides
only
temporary
relief
from
hypoglycaemia
and
should
always
be
followed
by
oral
▪
Most
women
are
managed
with
basal
bolus
regimens
using
fast-acting
insulin
analogues
(Humalog®
insulin
lispro,
Novorapid®
insulin
aspart)
taken
with
meals.
▪
The
long-acting
insulin
analogues
detemir
and
glargine
are
the
long-acting
insulins
of
choice
in
pregnancy.
▪
Glargine
dose
is
often
divided
into
a
BD
regime
from
ws
16
to
20
in
order
to
achieve
good
preprandial
control.
▪
In
some
countries
NPG
(isophane)
insulin
is
still
used
in
pregnancy
and
this
is
also
often
used
as
a
BD
regime.
▪
Insulin
often
need
to
be
increased
in
the
presence
of
infection,
use
of
corticosteroids
▪
Women
should
be
offered
blood
ketone
testing
strips
and
a
meter
and
advised
to
test
for
ketonaemia
if
they
become
hyperglycaemic
or
unwell.

18. ▪
Management
of
type
2
diabetes
▪
Most
women
require
tt
with
insulin
during
pregnancy.
▪
Metformin
▪
biguanide
can
be
used
as
an
adjunct
or
alternative
to
insulin
(NICE).
▪
Thiazolidinediones
▪
e.g.,
rosiglitazone,
pioglitazone
▪
reduce
peripheral
insulin
resistance.
▪
Out
with
pregnancy
they
are
used
as
2
nd
line
therapy
added
to
either
metformin
or
sulphonylureas
▪
Their
use
is
avoided
in
pregnancy.
▪
Sitagliptin
▪
dipeptidyl
peptidase-4
(DPP-4)
inhibitor
increasing
the
production
of
insulin
and
decreasing
the
production
of
glucagon
by
the
pancreas.
▪
It
is
also
avoided
in
pregnancy.
▪
Glucagon-like
peptide-1
(GLP-1)
receptor
agonists
and
SGLT2
inhibitors
are
also
avoided
in
pregnancy.
2.
Prevention
of
Diabetic
complications
▪
Retinopathy:
▪
ophthalmological
examination
with
digital
imaging
of
the
retina
with
mydriasis
using
tropicamide
pre-pregnancy
and
in
early
pregnancy
if
their
annual
assessment
occurred
more
than
3
months
previously
and
at
28
weeks.
If
diabetic
retinopathy
is
present,
the
next
assessment
should
be
at
16–20
weeks.
Laser
photocoagulation
can
be
used
either
to
treat
or
prevent
proliferative
retinopathy
in
pregnancy.
▪
Diabetic
retinopathy
is
not
a
contraindication
to
rapid
optimization
of
glycaemic
control
nor
to
vaginal
delivery.
▪
Women
with
pre-proliferative
diabetic
retinopathy
should
have
ophthalmological
follow
up
for
at
least
6
months
postpartum.

19. ▪
Nephropathy:
▪
Referral
to
a
nephrologist
pre-pregnancy
or
in
early
pregnancy
if
the
serum
creatinine
is
≥120
μmol/L
or
the
protein
leak
is
>0.5
g/day
or
albumin
creatinine
ratio
[ACR]
>
30
mg/mmol.
▪
Women
with
diabetic
nephropathy:
▪
regular
monitoring
of
renal
function
▪
quantification
of
proteinuria
(protein
creatinine
ratio
[PCR]
or
albumin
creatinine
ratio
▪
Hypertension
▪
30%
of
women
with
diabetic
nephropathy
▪
75%
will
develop
hypertension
by
the
end
of
pregnancy.
▪
Strict
control
of
hypertension
in
pregnancy
is
important
to
prevent
ongoing
renal
damage.
▪
Therefore
in
hypertensive
or
nephropathic
women
with
diabetes,
a
low
threshold
for
antihypertensive
therapy
(e.g.,
135/85)
is
used.

20. 2.
Obstetrical
management
Antenatal
1.
Regular
BP
and
urinalysis
checks
to
detect
PET
2.
US:
1.
Dating
&
viability
scan:
early
2.
NT
scan:
at
11–13
w
3.
Anomaly
scan
at
18–20
w’,
including
4-chambered
assessment
of
f
heart.
4.
Regular
scans
for
f
growth
and
liquor
volume
in
the
third
trimester
(e.g.
28,
32,
and
36
w)
to
detect
macrosomia
and
polyhydramnios
3.
Low-dose
aspirin
to
all
women
with
diabetes
{increased
risk
of
PET}.
4.
Corticosteroids
▪
to
induce
fetal
lung
maturation
▪
additional
insulin
prescribed
▪
close
monitoring
to
avoid
severe
hyperglycaemia
and
DKA.

21. II.
Intrapartum
❑
Timing
and
mode
of
delivery
▪should
be
individualized,
based
on
▪EFW
▪obstetric
factors
▪previous
mode
of
delivery
▪Gestation
▪glycaemic
control
▪antenatal
complications
▪Balance
the
risks
of
▪PTL
and
its
associated
complications
▪late
IUD
and
macrosomia
with
its
complications.
❑Timing
of
delivery
(NICE)
▪
induction
of
labour
or
elective
CS
if
indicated
between
37
and
38
+
6
w
for
women
with
▪
no
maternal
or
fetal
complications
▪
good
glycaemic
control.
▪
Delivery
should
be
expedited
if
complications
occur.

22. ❑Mode
of
delivery
▪Vaginal
delivery
is
preferred.
▪Continuous
electronic
fetal
monitoring
▪Shoulder
dystocia
▪more
common
at
all
birth
weights
than
in
the
non-diabetic
population.
▪
CS:
(both
elective
and
emergency)
are
increased
▪
Overall:
67%
▪
Emergency:
38%.
▪
{high
rate
of
macrosomia
(21%
of
babies
weighed
more
than
4
kg;
6%
>4.5
kg),
this
high
rate
may
be
unavoidable.
▪Elective
CS
if
▪EFW
is
>4.5kg.
▪EFW
is
4–4.5kg
use
obstetric
factors
to
influence
decision.
▪Antibiotic
and
thromboprophylaxis

23. ❑
Glycaemic
control
▪
type
2
diabetes
An
insulin
infusion
is
not
usually
required
▪
type
1
diabetes
▪
sliding
scale/variable
rate
insulin
infusion.
▪
IV
infusions
of
short-acting
insulin
and
dextrose
are
administered
throughout
active
labour
and
delivery
via
separate
giving
sets,
to
allow
acceleration
of
glucose
infusion
and
cessation
of
insulin
in
the
event
of
hypoglycaemia.
▪
women
using
insulin
pumps:
continue
these
in
labour
but
to
discontinue
for
CS.
▪
The
capillary
blood
glucose
should
be
estimated
hourly,
and
the
insulin
infusion
rate
altered
according
to
a
sliding
scale
determined
by
the
individual
daily
insulin
requirements.
▪
The
usual
dose
range
is
2–6
U/hr.
▪
The
target
glucose
level
during
labour
and
delivery
is
4–7
mmol/L
(72-126mg/dl),
the
aim
being
to
avoid
hypoglycaemia.
▪
The
dextrose
infusion
(5%
or
10%)
should
provide
500
mL
of
fluid
every
8
hours.
▪
Insulin
drives
extracellular
potassium
into
the
cells.
It
is
important,
therefore,
to
include
potassium
replacement
with
the
i.v.
dextrose
to
avoid
hypokalaemia
which
may
otherwise
result
especially
if
glucose
levels
are
high.

24. III.
Post-partum
care
▪Baby
▪early
feeding
▪glucose
monitoring.
▪Breast-feeding
▪Encourage
▪Avoid
oral
hypoglycaemic
drugs
if
breastfeeding
▪metformin
and
insulin
are
safe.
▪
Type
1
diabetes
▪
Following
delivery
of
the
placenta,
the
rate
of
infusion
of
insulin
is
halved
▪
Postpartum,
insulin
requirements
return
rapidly
to
pre-pregnancy
levels.
▪
Once
women
are
eating
normally,
SC
insulin
at
either
the
pre-pregnancy
dose
or
at
a
25%–40%
lower
dose
if
the
women
intends
to
breastfeed,
which
is
associated
with
increased
energy
expenditure.
▪
type
2
diabetes
▪
who
are
breastfeeding
can
resume
or
continue
taking
metformin
or
glibenclamide
(glyburide).
▪
Other
oral
hypoglycaemic
drugs
are
avoided
in
breast
feeding.

25. ▪Contraception
•
Avoid
the
COCP
if
▪breast-feeding
or
▪vascular
complications.
▪Progesterone-based
contraception
Safe
▪No
contraindications
to
an
IUCD.
▪should
be
fitted
from
6w
post-partum
onwards.
▪Sterilization
or
vasectomy
▪should
be
considered
if
the
family
is
complete.