Pre- Existing Type 1 and Type 2

Diabetes in Pregnancy
DR. P. MANJULA GUNARATNE
MBBS(COLOMBO), MRCOG(UK)

Introduction
Diabetes is the most common significant medical

disorder in pregnancy
The prevalence of both type 1 and type 2 diabetes are
increasing

WHO definition of Diabetes Mellitus

Normal

Fasting
(mmol/l)
<6.1

2 hour
(mmol/l)
<7.1

Impaired glucose tolerance

<7.0

7.8-11.1

Impaired fasting glucose

6.1-7.0

<7.8

Diabetes Mellitus

>7.0

>11.1

Physiology of Glucose Metabolism

In pregnancy physiology of glucose metabolism alters
Initially there is a reduction in fasting glucose (by about 10-20%) due

to

Increased renal clearance

Decreased gluconeogenesis.
Increased glucose uptake from maternal circulation by the growing fetus
Increased peripheral glucose uptake
Increased glycogenesis

This puts type 1 diabetic woman at risk of hypoglycaemia in the first

trimester
As pregnancy progresses the womans insulin requirements increases
as pregnancy is a state of insulin resistance due to placental production
of diabetogenic hormones

Human placental lactogen,

Cortisol,
Progesterone
Growth Hormone

Physiology Conti
Therefore carbohydrate metabolism later in pregnancy directed towards

providing the growing fetus with glucose and amino acids and liberating
more fatty acids, ketone bodies and glycerol as substrate for maternal energy
The insulin mediated glucose uptake into skeletal muscle also fall in
pregnancy
Non diabetic women increase their post-prandial insulin production by 50%
to counteract this
Women with diabetes are unable to mount an adequate response to
hyperglycaemia due to absence (type 1) or reduction (type 2)of functioning
beta cells
Women with type 1 diabetes will need to increase their dose to counteract
this physiological change
Type 2 diabetic women will usually require insulin during pregnancy to
achieve normoglycaemia

Effects of pregnancy on Diabetes

Diabetic ketoacidosis
Hypoglycaemia
Renal Impairment
Retinopathy

Diabetic Ketoacidosis
Diagnosis should be considered in any pregnant women with type 1 diabetes who becomes

unwell
Causes in pregnancy include

Hyperemesis gravidarum
Infections
Corticosteroids
Beta mimetics

Ketones

are present in pregnancy even in non diabetic women due to enhanced lipolysis
producing an increase in FFA and ketones
DKA is confirmed by raised blood glucose in the presence of reduced bicarbonate and raised
urinary ketones
DKA can present with severe dehydration and profound acidosis leading to organ
impairment and cardiac arrhythmias
Ketones cross the placenta and affect the fetus at high levels
Fetal monitoring during maternal DKA has showed an absence of variability of heart rate and
late decelerations. These reverse after the woman is treated and so immediate delivery is not
warranted until after maternal metabolic abnormalities have normalized
DKA treated with

IV glucose and insulin via a sliding scale

Serum potassium levels need to be closely monitored as insulin drives potassium into the cells and this should
be replaced intravenously

Hypoglycaemia
Diagnosed when blood glucose < 3.9mmol/l
In early pregnancy hypoglycaemia is more common due

to

Rapid improvement in glucose control to prevent congenital

abnormalities
Reduced hypoglycaemic awareness

To prevent severe hypoglycaemia

Insulin dose may need to reduce

They should be given concentrated glucose solution for
emergencies
They should be prescribed a glucagon injection with partner or
family members instructed how to administer

Renal Impairment
Diabetic nephropathy is usually a progressive disease and

divided into

Microalbuminuria albumin creatinine ratio 3.5-30mg/mmol

Macroalbuminuria- ACR >30mg/mmol
End stage renal failure raised serum creatinine and uraemia

Diabetic nephropathy in pregnancy is associated with

increased incidence of

Pre-eclampsia
Adverse fetal outcome
Risk of progression of maternal renal disease

Those women with diabetic nephropathy

Mild renal impairment usually reversible post pregnancy

Advanced nephropathy can lead to irreversible progression

Retinopathy
The prevalence of diabetic retinopathy increases

progressively with increasing duration of diabetes

Retinopathy starts to occur in type 1 after 3-5 years
and most patients will have some retinopathy at 20
years. Less women with type 2 found to have
retinopathy
In pregnancy there is a potential for retinopathy to
progress

Effects of Diabetes on Pregnancy

Maternal complications
Fetal complications

Maternal complications
Severe hypoglycaemia and hypoglycaemic unawareness during

pregnancy
Diabetic ketoacidosis
Retinopathy
Nephropathy
Miscarriage rates are higher in diabetic women with high
HbA1c at the start of pregnancy
Pre-eclampsia- increased particularly women with renal disease
and hypertension pre-pregnancy and obesity
Infections- increased incidence of UTI & post operative wound
infection
Caesarean section- increased

Fetal complications
Fetal loss
Congenital malformations

diabetes associated with 3-5 fold increase incidence of congenital

abnormalities
Main defects are cardiac, neural tube defects, malformations of GIT,
urinary & musculoskeletal systems
Hyperglycaemia is toxic environment to developing embryo

Macrosomia & Shoulder dystocia

Glucose transferred across placenta by facilitated diffusion to fetus

Maternal hyperglycaemia lead to fetal hyperglycaemia and fetus respond
to high glucose levels by secreting more insulin
Insulin is a growth factor and high levels stimulate fetal growth leading to
macrosomia
Macrosomia is associated with increased incidence of shoulder dystocia,
Erbs palsy, prolonged labour, polyhydramnios and asphyxia

Stillbirth

Most frequent between 32-36 week

Pre-eclampsia
Polyhydramnios
Obstructed labour
Hypoglycaemia
Respiratory distress syndrome
Jaundice

Management
Pre-pregnancy
Antenatal
Labour & Delivery
Postnatal

Pre-pregnancy Management
Folic Acid

Women with diabetes have high incidence of NTD

They should be prescribed higher dose of folic acid pre-conceptually until 12 weeks (5mg/day)
(NICE recommendation)

Glycaemic control

HbA1c reflects glucose control over last 3 months

Women should aim HbA1c <6.1 (NICE recommendation)
women who are planning to become pregnant should be offered monthly HbA1c measurements.
(NICE recommendations)
Once pregnancy is achieved HbA1c should not be used as it is no longer accurate and insulin
adjustments should be according to blood glucose values
Those with HbA1c >10% should be advised to avoid pregnancy (NICE recommendation)
Women with type 1 diabetes who are planning to become pregnant should be offered ketone
testing strips and advised to test for ketonuria or ketonaemia if they become hyperhglycaemic or
unwell (NICE recommendation)

Retinal assessment

They should be offered annual retinal assessment (NICE recommendation)

Renal assessment (NICE recommendation)

Offer renal assessment including microalbuminuria

If serum creatinine >120umol/l or eGFR <45ml/minute/1.73m 2 refer to nephrologist

Pre-pregnancy Management Conti..

Diet, Body weight, Exercise

Those with BMI>27kg/m2 advise to loose weight (NICE recommendation)

Medications

ACE inhibitors or Angiotensin receptor blockers

Statins(HMG CoA reductase inhibitor)

Should not be used in pregnancy as they are associated with oligohydramnios, renal failure, hypotension and
skull defects in fetus
Traditional advice was to take ACEI until a positive pregnancy test and then stop
But new evidence suggest this practice is not safe and women should not conceive on ACEI
The only exception may be women with heavy proteinuria controlled on ACEI and nephrologist should review
the case
NICE recommends ACE inhibitors and Angiotensin receptor blockers should be stopped before conception or
as soon as pregnancy is confirmed
Alternative antihypertensives are methydopa, nifidipine, labetolol
To reduce cholesterol levels
Discontinue them pre-conceptually as they are associated with CNS and limb deficiencies in the fetus
NICE recommends to discontinue statins before conception or as soon as pregnancy confirmed

Metformin

Can be used pre-conception and during pregnancy (NICE recommendation)

Antenatal Management
The pregnancies should be jointly managed with obstetrician,

midwife, dietician, diabetic nurse and diabetologist

NICE target blood glucose measurements

Fasting

3.5-5.9mmol/l

1 hour post-meal

<7.8mmol/l

HbA1c should not be used routinely for assessing glycaemic

control in 2nd & 3rd trimesters (NICE recommendation)

Glycaemic Control
Aim should be to achieve euglycaemia safely in pregnancy to prevent

maternal and fetal morbidity

Women with type 1 diabetes

Will already be on insulin and possible regimens are

Twice a day mixed insulin combination of long and short acting insulin
Basal bolus regimen short acting insulin with each meal and long acting insulin at
night
Insulin pump short acting insulin in a pump infusing subcutaneously continuously at
a low rate with boluses pre-meal

NICE recommends offering pumps in pregnancy if adequate glycaemic control

cannot be achieved on basal bolus regimen without significant disabling
hypoglycaemia
Maternal insulin does not cross placenta

The problem with human insulin are the slow onset and long duration of action that
puts the patient at risk of hypoglycaemia and production of antibodies
Newer analogues mimic bodys own insulin secretion and associated with less
hypoglycaemic events

Glycaemic Control Conti..

Women with type 2 Diabetes

They may be on sulphonylureas (gliclazide, glibenclamide), biguanides

(metformin), alpha glucosidase inhibitors, thiazolidinediones, maglitinides, GLP-1
analogues and DPP-IV inhibitors
During pre-pregnancy they should stop all above medications except metformin
and glibenclamide

NICE recommendation

Advise women to check fasting and 1 hour post prandial during pregnancy
Those treated with insulin should check blood glucose levels before going to bed at
night
Women with type 1 diabetes should check ketonuria or ketonaemia if they become
hyperglycaemic or unwell
Women with insulin treated diabetes should be provided with concentrated glucose
solution and women with type 1 diabetes should be given glucogon and instruct
family members how to use it

Dietary advice and weight management

Dietician review recommends in all cases

Screen for maternal complications

Prescription of low dose Aspirin should be considered in those with

additional risk factors for pre-eclampsia

Renal assessment (NICE recommendation)

Baseline renal function and urinary protein quantification at the beginning of

pregnancy should be done
Serum creatinine >120umol/l or protein excretion >2g/day refer to nephrologist
Consider thromboprophylaxis if >5g/day proteinuria (macroalbuminuria)

Retinal screening (NICE recommendation)

At first ANC if they have not seen last 6 months
If any retinopathy present additional testing should be performed at 16-20 weeks
Repeat at 28 weeks if first examination is normal
Diabetic retinopathy is not a contraindication for rapid optimisation of blood
glucose
Women who had proliferative diabetic retinopathy should have ophthalmological
follow up for at least 6 months following delivery

Screen for Fetal Complications

Ultrasound scans (NICE recommendation)

Fetal cardiac scan if abnormalities detected at anomaly scan.

Look for 4 chamber view of heart and outflow tract
Monitor fetal growth at 28.32,36 weeks

Labour & Delivery

Induction

NICE recommends delivery after 38 completed weeks

Shoulder dystocia is a recognized complication
They have higher incidence of Caesarean section

Steroid administration

For fetal lung maturation can lead to type 1 diabetic developing DKA
This can be reduced by

Increasing SC insulin (for 5 days post injection)

Insulin sliding scale regimen

Glycaemic control peri-delivery

Strict glycaemic control during labour & delivery is vital to prevent neonatal
hypoglycaemia
Blood glucose should be kept between 4-7mmol/l (NICE recommendation)
They may need insulin dextrose infusion in sliding scale
Neonatal hypoglycaemia is due to maternal hyperglycaemia driving fetal pancreas to
produce increased amount of insulin. Post delivery the fetus needs time to down
regulate insulin production and this lag period exposes the fetus to hypoglycaemia

Postnatal
Women with diabetes need to stay in hospital for at least 24 hours post-

delivery to assess that the baby is maintaining normoglycaemia and

feeding is established
Post-delivery insulin resistance falls due to the absence of placental
hormones, and therefore women should convert back to pre-pregnancy
regimen
Type 1 diabetics should be warned about the potential for hypoglycaemia
when breastfeeding and advised to eat prior to feeding and have a snack
available
Type 2 diabetics can continue taking metformin
Glipizide and glibenclamide are not detected in breast milk and therefore
are safe in breastfeeding
All other oral hypoglycaemic agents should be avoided until after
breastfeeding is discontinued

References
Pre-existing type 1 and type 2 diabetes in

pregnancy : Kimberley Lambert, Sarah Germain :

Obstetrics, Gynaecology & Reproductive Medicine ,
december 2010
Diabetes in Pregnancy : NICE Guideline 63 :March
2008
Pre-existing (Type 1 and type 2) diabetes in
pregnancy: P Gilby, P V Carroll: Obstetrics
Gynaecology and Reproductive Medicine: December
2007

Thank You