Foetus needs 3 critical substrates for growth

• Oxygen – simple diffusion

• Glucose – Facilitated diffusion
• Amino acids – Active transport

Foetus burns glucose with Oxygen to create

energy  Adenosine Tri Phosphate (ATP)
ATP is used on aminoacids (esp Alanine) to
build proteins for growth
• Indian women –risk of developing GDM is
.

11.3 times compared to white women

• The prevalence of GDM in India varied from

3.8 to 21% in different parts of the
country, depending on the geographical
locations and diagnostic methods used.
(16.55%)

• GDM has been found to be more prevalent in

urban areas than in rural areas
 Effects on mother

• Repeated infections –------Urinary Tract Infection

Vaginal – Candidiasis

• Pre eclampsia –----- Plasma Angiotensin is

directly proportional to
blood glucose concentration

• Hydramnios--------------- Foetal polyuria

Large plcenta
Neural tube defect
 Effects on mother

• Preterm labour ------- vasculopathy

• Mal presentation
• CPD ------ macrosomia
• Traumatic delivery

• Retinopathy ---- BDR -> BDR -> PDR

• Nephropathy
 Effects on Foetus
• Abortions
• Malformations

Disruption of the normal function of the yolk sac

Oxidative metabolism and generation

of free oxygen radicals which are toxic

Glucose induced mutations in embryonic DNA

 .

System Type of anomaly Timing of lesion

(weeks post
conception)
Skeletal Caudal regression 3
Spina bifida 6
Neural Anencephaly 4
Myelocele 4
Hydrocephalus 5
Cardiovascular Dextrocardia 4
Conus arteriosus 5
Ventricular septal 6
Renal Agenesis/Hypoplasia 6
 To avoid fuel mediated teratogenesis

Pre pregnancy counselling

Excellent control of maternal metabolism

Folic acid supplementation

Anti oxidants

7.5% --- 0.8%

 Effects on Foetus
• Macrosomia
• Plethora

Insulin --- 11th week of gestation

Pancreatic foetal mass

Insulin secretion 16th week ---26th week

Dysfunction of anterior pituitary --- growth hormone

 .

Intra uterine foetal demise ---

Ketosis in mother
Metabolic disturbance in foetus - acidosis
Foetal blood hyperviscosity
Hormonal imbalance
Pre eclampsia
Universal screening for GDM is essential, as
it is generally accepted that women of
Asian origin and especially ethnic Indians,
are at a higher risk of developing GDM
and subsequent type 2 diabetes
 Universal screening for GDM
ADA procedure
ADA recommends two step procedures.
Step 1: A 50 g glucose challenge test (GCT) is used for
screening without regard to the time of last meal or time
of the day .
Step 2: If 1 hour GCT value is more than 140 mg/dl, 100g
Oral Glucose ToleranceTest (OGTT) is recommended and
plasma glucose is estimated at 0, 1, 2 and 3 hours.
Gestational Diabetes Mellitus is diagnosed (Carpenter and
Coustan criteria) if any 2
values meet or exceed
FPG > 95 mg/dl, 1 hr PG > 180 mg/dl, 2 hr PG > 155 mg/dl
and 3 hr PG > 140 mg/dl.
The drawback of this criteria is that, the glycemic
.

cut off
was originally validated against the future risk of
these women developing diabetes and not on
the fetal outcome .
Further, in the community health centers,
pregnant women are reluctant to undergo ADA
procedures for two reasons
1. The number of blood samples drawn are many
(a) for screening and (b) forsubsequent 3- hour
OGTT to confirm the diagnosis (4 blood samples).
2. They have to visit the ante-natal clinic on two
occasions – (a) for screening and (b) again for
diagnostic procedure.
To standardize the .

diagnosis of GDM, the World Health Organization

(WHO) recommends using a 2 hour 75 gm OGTT
with a threshold plasma glucose concentration of
greater than 140 mg/dl at 2 hours, similar to that
of IGT ( > 140 & < 199 mg/dl), outside pregnancy
WHO procedure also has a shortcoming in that, the
criteria suggested for diagnosis of GDM was also
not based on the maternal and fetal outcome but
probably the criteria was recommended for its easy
adaptability in clinical practice
A single test procedure to diagnose gestational
.

diabetes mellitus in the community

Seldom, a pregnant woman visiting the ante-
natal clinic for the first time comes in the
fasting state. If she is asked to come on
another day in the fasting state she maynot
return . Hence it is important to have a test
that detects the glucose intolerance without
the woman necessarily undergoing a test in
the fasting state and it is preferable to
perform the diagnostic test at the first visit
itself.
In the antenatal clinic, a pregnant woman after
undergoing preliminary clinical
examination, has to be given a 75g oral glucose
load*, without regard to the time of
the last meal. A venous blood sample is
collected at 2 hours for estimating plasma
glucose by the GOD-POD method. GDM is
diagnosed if 2 hr plasma glucose is 140
mg/dl.
Performing this test procedure in the non-fasting state is rational, as glucose
concentrations are affected little by the. time since the last meal in a normal
glucose
tolerant woman, whereas it will, in a woman with gestational diabetes .

After a meal, a normal glucose tolerant woman would be able to maintain

euglycemia despite glucose challenge due to brisk and adequate insulin
response, whereas, a woman with GDM who has impaired insulin
secretion . her glycemic level increases with a meal and with glucose
challenge, the glycemic excursion exaggerates further .

Therefore, this procedure assumes clinical relevance as

WHO criteria based on glucose concentration 2 h after 75 g glucose load was
able to correctly identify subjects with GDM.

Yet another reason for recommending the single step procedure is that, the
specificity of ADA screening with 50 gm 1-hr GCT without regard to time
of the last meal is low.
.
• ADVANTAGES
• The pregnant women need not be fasting.
• Causes least disturbance in a pregnant
woman’s routine activities.
• Serves as both screening and diagnostic
procedure.
 .

With 75 gm OGTT (WHO criteria)

Plasma Glucose InPregnancy OutsidePregnancy

2 hr > 200 mg/dl Diabetes Diabetes

2 hr > 140 mg/dl &
< 199 mg/dl GDM IGT
2 hr >120 mg/dl &
< 139 mg/dl GGI —
2 hr < 120 mg/dl Normal Normal
• By following the usual recommendation for
.

screening between 24 and 28 weeks of gestation,

the chance of detecting unrecognized type 2
diabetes before pregnancy (pre- GDM) is likely to
be missed .
• If the 2 – h PG is > 200 mg/dl in the early weeks of
pregnancy, she may be a pre-GDM and A1c of > 6 is
confirmatory
• {Normal A1c levels during pregnancy is 5.3 - 6}.
• A pregnant woman found to have normal glucose
tolerance [NGT], in the first trimester, should be
tested for GDM again around 24th – 28th week
and finally around 32nd – 34th week.
Patient Education .

The compliance with the treatment plan depends on the

patient’s understanding of:

· The implications of GDM for her baby and herself

· The dietary and exercise recommendations
· Self monitoring of blood glucose
· Self administration of insulin and adjustment of insulin doses
· Identification and treatment of hypoglycemia (patient and
family members)
· Incorporate safe physical activity (walking at usual pace/arm
exercise)
· Development of techniques to reduce stress and cope with
the denial.
Care should be taken to minimize the anxiety of the women.
Target Blood Glucose Levels
.

The occurrence of birth weight > 90th

percentile (macrosomia) was continuum as
fasting plasma glucose increased > 90
mg/dl [50] and the 2 hr plasma glucose > 120
mg/dl .
Thus, maintenance of Mean Plasma Glucose
(MPG) level ~ 105 to 110 mg/dl is desirable for
a good fetal outcome.
This is possible if FPG and 2 hour post prandial
peaks are ~90 mg/dl and ~120 mg/dl
respectively.
Medical Nutrition Therapy (MNT)
a) General Principles: All women with GDM
.
should receive nutritional
counseling. The meal pattern should provide adequate calories and nutrients
to meet the needs of pregnancy.
The expected weight gain during pregnancy is 300 to 400 gm/week and total
weight gain is 10 to 12 kg by term.

Hence the meal plan aims to provide sufficient calories to sustain adequate
nutrition for the mother and fetus and to avoid excess weight gain and
post prandial hyperglycemia.

Calorie requirement depends on age, activity, pre pregnancy weight and

stage of pregnancy.
Approximately 30 to 40 Kcal/kg ideal body weight or an increment of 300
kcal/day above the basal requirement is needed in 2nd and 3rd
trimesters.
Pregnancy is not the ideal time for obesity correction.

Underweight subjects or those not gaining weight as expected,

particularly in the third trimester, require admission to ensure adequate
nutrition to prevent low birth weight infants.
Calorie Counting:
.

As a part of the medical nutrition therapy, pregnant diabetic

woman are advised to wisely distribute their calorie consumption
especially
the breakfast. This implies splitting the usual breakfast into two equal
halves
and consuming the portions with a two hour gap in between.

By this the undue peak in plasma glucose levels after ingestion of the total
quantity is avoided.
The two hours post prandial plasma glucose falls by 20 – 30 mg/dl.

More than 90 % of GDM can be managed by MNT (Observation from

the Diabetes in Pregnancy Awareness & Prevention [DIPAP] Project,
supported by the Government of Tamil Nadu and World Diabetes
Foundation [WDF]).
Explanatory note: .

This advice, of splitting the breakfast into two

portions, has scientific basis as the peaking of
plasma glucose is high with breakfast (due to
dawn phenomenon) than with lunch and dinner.

In a normal person, insulin secretion is higher with

breakfast than with lunch or dinner , whereas,
GDM mothers have deficiency in first phase
insulin secretion and to match this insulin
deficiency the challenge of quantity of
food at one time should also be less.
• Dawn phenomenon, sometimes called the dawn effect,
is an early-morning (usually between 2 a.m. and 8 a.m.)
.

increase in blood sugar (glucose) relevant to people with

diabetes.
• Dawn phenomenon is caused
• by the release of counter regulatory hormones such as
cortisol, glucagon, or epinephrine, all of which can signal
the liver to release glucose.
• by insufficient insulin administration the night before,
incorrect medication dosages,
• by eating carbohydrate snacks at bedtime.
• Dawn phenomenon can be managed in many patients by
avoiding carbohydrate intake at bedtime, adjusting the
dosage of medication or insulin, switching to a different
medication, or by using an insulin pump to administer
extra insulin during early-morning hours.
Initiating Insulin Therapy
.
Once diagnosis is made, medical nutritional therapy (MNT) is
advised initially for
two weeks.
If MNT fails to achieve control , insulin may be initiated.

A. Preferable to start with Premix insulin 30/70 of any brand.

Starting dose: 4 units before breakfast
Every 4th day increase 2 units till 10 units
If FPG remains > 90 mg/dl advised 6 units before breakfast & 4
units before dinner
Review with blood sugar test Adjust dose further

Total insulin dose per day can be divided as 2/3 in the morning
and 1/3 in the evening.
* Initially if Post breakfast plasma glucose is high Start Premix
50/50
B. If GDM is diagnosed in the third trimester,
.

MNT is advised for a week.

Insulin is initiated if MNT fails.

C. If 2- hour PG > 200 mg/dl at diagnosis, a

starting dose of 8 units of premixed
insulin could be administered straightaway
before breakfast and the dose has to be
titrated on follow-up. Along with insulin therapy,
MNT is also advised.
Insulin Analogs .

If Post prandial glucose is still not under control –

consider using rapid-acting insulin analogs.
Rapid acting insulin analogues, (Aspart - Novorapid/
Lispro -Humalog) have been found to be safe and
effective in achieving the targeted post prandial
glucose value
during pregnancy .
Lispro analogue is approved by US FDA
Aspart has been approved for use in pregnancy both
by US FDA and European Union.
Pen injectors are very useful and the patient’s
acceptance is excellent.
Note:
.

1. Usually women with gestational diabetes do not require > 20 units of

insulin per day for glycemic control

2. Pre-gestational diabetic women during pregnancy may require high dose

of insulin. A few may require Multiple-Daily Injections (MDIs), usually
given as short acting insulin before breakfast and lunch and intermediate–
acting insulin or pre-mix before dinner.

3. Insulin dose is always individualized and has to be adjusted on follow-up.

4. If insulin requirement drops, placental insufficiency or fetal jeopardy has

to be suspected (may also be due to increased utilization of maternal
glucose by the supercharged beta cell mass of the macrosomic fetus –
“fetal handling of maternal glucose”
• GDM women usually have high post breakfast plasma glucose level
compared to
• post lunch and post dinner. The period between breakfast and lunch is
often
• problematical because of the physiological tendency to hyperglycemia at
this time,
• and may necessitate substantial increases in the morning dose of short-
acting
• insulin, together with careful adjustment of meal timing and snacks to
avoid
• hypoglycemia [40]. A few GDM women may have high post lunch and
dinner
• plasma glucose. Insulin dose has to be adjusted by frequent monitoring of
• postprandial blood glucose.
• Insulin secretagogue [Glybenclamide]
• A randomized unblinded clinical trial compared the use
of insulin and glyburide in
• women with GDM who were not able to meet glycemic
goals on meal plan.
• Treatment with either agent resulted in similar
perinatal outcomes. All these patients
• were beyond the first trimester of pregnancy at the
initiation of therapy [64].
• Publications on other drugs belonging to this group are
dismal.
Metformin .

A randomized controlled study found that in women with

gestational diabetes mellitus, metformin (alone or with
supplemental insulin) was not associated with
increased perinatal complications as compared with insulin
.
Metformin has been found to be useful in women with
polycystic ovarian disease (PCOD) who failed to
Conceive .
Continuing this drug after conception is still a controversy,
but there are a few studies favoring continuation of
metformin throughout pregnancy in these women

More studies are required before routinely ecommending

oral anti-diabetic drugs during pregnancy.
Measuring Other Parameters
.
MATERNAL
If the glucose intolerance is detected in the early pregnancy,
A1c level will be helpful to differentiate between a pre gestational
diabetic and GDM.
If the A1c level is more than 6%, she is likely to be a pre GDM.

A1c is useful in monitoring the glucose control during pregnancy, but

not for the day to day management. A1c level may serve as a
prognostic value.

The blood pressure has to be monitored during every visit. If blood

pressure is found to be more than 130/80, advise alpha-
methyldopa 125 mg and dose to be adjusted on follow-up.

Examination of the fundus and estimation of microalbuminuria,

every trimester is recommended particularly in women with
pregestational diabetes.
FETAL .

Fetal Surveillance:
Ultrasound Fetal Measurement: Ultrasound monitoring is
recommended every trimester.

A fetal echo is a must at 24 week, especially in prediabetics

to rule out cardiac defects
.
Foetal biophysical profile in the late trimester is advisable.

Doppler umbilical blood flow measurement or

cardiotocograph [CTG] may be performed around 36 weeks
of gestation in GDM with other pregnancy complications
such as pre-eclampsia, hypertension, antepartum
hemorrhage and intrauterine growth retardation.
 .
Plasma Glucose and Insulin IV Fluid
PLASMA GLUCOSE INSULIN / IV FLUIDS
At time of onset of labour
< 70 mg/dl 5% GNS - 100 ml/hr
90-120 mg/dl NS - 100 ml/hr
120-140 mg/dl NS -100 ml/hr plus
4 units of Reg. Insulin

140-180 mg/dl NS - 100 ml/hr plus

6 units of Reg. Insulin

>180 mg/dl NS - 100 ml/hr plus

8 units of Reg. Insulin
Drip rate: 16 to 20 drops per minute.
Maternal Capillary blood glucose to be checked by
glucometer every 1 hour and drip rate adjusted.