DIABETES IN PREGNANCY

Maternal Diabetes
Two lives.. Twice as special
An oppurtunity for primary prevention

-Maternal health
-Child health
 Definition
GDM is defined as carbohydrate in tolerance of variable severity
with onset or first recognition during pregnancy.

The definition is applicable regardless of whether insulin is used

to treat the disease or if the condition persists after pregnancy.

It does not exclude the possibility that unrecognized glucose

intolerance may have antedated the pregnancy
 Introduction
• Incidence of GDM is variable from 17% to 29%
of all pregnancies
• Associated with maternal and perinatal compli
cations.
• 90% of all Diabetics are GDM and 10% are due
to pregestational diabetes.
• 4 million pregnancies in India are complicated
by GDM
• This may contribute a part of MMR in India
 GDM prevalence linked to background IGT rates

GDM IGT
2% 2%
1980s Agarwal S, Gupta AN. Gestational Dia Ramachandran A, et .al., High prevalence of di
betes. J Assoc Physicians India 1982;3 abetes in an urban population in south India. B
0:203 MJ 1988;3; 297(6648):587-90

7.6% 8.2%
1990s Narendra J, Munichoodappa C, et al, Prevalence of
glucose intolerance during pregnancy. Int J Diab Dev
Ramachandran A, Snehalatha c, Dharmaraj D, Viswa
nathan M. Prevalence of glucose intolerance in Asian
Countries 1991;11:2-4 Indians. Diabetes Care 1992; 15:1348-55

16.6% 14.5%
V Seshiah, V Balaji, Madhuri S Balaji, CB Sanjeevi, A. Ramachandran A, Snehalatha C, Kapur A, Vijay V, Moha
2000s Green. Gestational Diabetes Mellitus in India. J Assoc n V,Das AK, Rao PV, Yajnik CS, Prasanna Kumar KM, Nai
Physicians India 2004;52:707 r JD.For the Diabetes Epidemiology Study Group in India
(DESI).Diabetologia 2001;44:1094-1101.
Significance of Diabetes and Pregnancy
• Malformation rate in 94/1000 Vs 9.7/1000 in general population

• Still birth is 15 times higher 25/1000 Vs 5/1000

• PNM is 3 times higher 19.9/1000 Vs 6.8/1000

• Recent concept of adult diseases having their origin inutero insults

has been established.

• 1989 WHO/IDF discussed the problem of hyperglycemia in pregnant

women. They wanted to achieve pregnancy outcome in diabetic wo
men same as in non diabetic women.
 FREINKEL HYPOTHESIS
Uterine At Birth After Birth

Macrosomia Obesity

Hypoglycemia
Maternal DM

Metabolic syndrome
placenta

A Insulin IGT/DM

A.A Fetus
Fat CVD
CHO
Diabetes and Pregnancy – Why it is relevant?
 IUGR & Macrosomia

Solution
Optimal nutrition+ Optimal glycemic cont
rol=Optimal birth weight
3000 – 3500 g.
SCREENING FOR DIABETES
 WHO Criteria

FPG (mg/dl) 2h PG (mg/dl)

IGT <126 140-200

Diabetes >126 >200

 ADA recommendation
Screening Procedure Criteria

Perform a 75-g OGTT , with The diagnosis of GDM is made

plasma glucose measurement when any of the following
fasting and at 1 and 2 h, at 24- plasma glucose values are
28 weeks of gestation in exceeded
women not previously
diagnosed with overt diabetes -Fasting >=
92mg/dL(5.1mmol/L)
The OGTT should be performed -1 hr >=180mg/dL(10.0
in the morning after an mmol/L)
overnight fast of at least 8 hrs. -2 hr>=153 mg/dL (8.5mmol/L)
THRESHOLDS FOR DIAGNOSIS OF GDM
 How to reduce this
• Early screening for GDM
• Monitoring frequently
• Proper uses of diet plan , exercise and insulin.
• Future concepts of CSII, CGMS, telemedicine,
e-health, will revolutionize the management of GD
M
 How to treat?
• MNT
• Exercise
• Insulin
• Glyburide
• Metformin
• Acarbose?
• Insulin pump
 Calorie allotment
• 30 kcal per kg current weight per day in pregnant
women who are BMI 22 to 25.
• 24 kcal per kg current weight per day in overweight
pregnant women (BMI 26 to 29).
• 12 to 15 kcal per kg current weight per day for severely
obese pregnant women (BMI >30).
• 40 kcal per kg current weight per day in pregnant
women who are less than BMI 22.

• Jovanovic-Peterson L, Peterson, CM. Nutritional

management of the obese gestational diabetic
woman. J Am Coll Nutr 1992; 11:246.
 How long MNT?
• Consensus and hard data are lacking regarding how long diet
therapy should be maintained before initiating pharmacologic
treatment.
• 70% of the subjects with initial fasting plasma glucose less th
an 95 mg/dL achieved targeted levels of glycemia within 2 we
eks of dietary management, but no significant improvement o
ccurred thereafter

• McFarland et al obstet gynecol 1999

Exercise Prescription
 Can continue prepregnancy
activity
 Keeping physically active is
essential for good glycemic
control
 Upperbody ergometric exe
rcise useful
 Do not start new vigorous e
xercise for glucose control
 Uterine contractions,fetal
tachy, maternal heart rate
to be monitored
 ORAL AGENTS IN
PREGNANCY
Glyburide study:
› Randomized trial glyburide vs insulin
› 404 GDMs FPG >95 but <140 mg/dl or 2-
hr pp >120 on diet
› Similar success of glucose control in both
groups

Langer et al: NEJM 200:343:1134

Animal insulin  Insulin Analogues
• 1920- Introduction of insulin revolutionized Di
abetes Management
• 1920- Introduced insulin had impurities and b
atch to batch variation
• 1980- higher quality insulin from bovine and p
orcine sources . Then came recombinant Insuli
n
 IDEAL AGENT SHOULD FULFILL
• Mimic physiological control
• No adverse effect upon maternal and fetal out
come.
• Should not interfere with antenatal , perinatal
and post natal care
• Insulin Analogues fulfills all the criteria when g
iven in right doses in right manner.
 ADVANTAGES
• Batch to Batch consistency
• No allergy, antibody formation
• No immune mediated lipoatrophy
• Glucose control is similar in endogenous insuli
n production
• Preprandial hypoglycemia and postprandial hy
perglycemia are well controlled.
• Mealtime flexibility is possible with analogues.
 Safety issues with Insulin Analogues
• Ideal insulin
- Mimic physiological insulin secretion
- Does not cross placenta
- No mitogenic potential
- Since IgG bound insulin can cross placenta, th
erapeutic agent should not induce antibody ge
neration
STRUCTURAL MODIFICATION OF INSULIN ANALOGUE

Insulin Lispro 28-29 Proline and Lysine are interchanged

Insulin Aspart Proline at 28 replaced by aspartic acid. (decreases hexamer

formation )
Insulin glulisine Position 3 of Lysine with Asparagine ; Lysine at 29 replaced by
glutamine
Insulin glargine Asparagine at A2 1 is replaced by glycine. 2 arginine added to C
terminal of Beta chain
Insulin detemir Binds with albumin. Threonine omitted at position 30th of Beta
chain and replaced by myristic acid at C 14 FA chain. (delays’
absorption by albumin binding)
Pharmacokinetics of HI and IA
RECEPTOR BINDING, METABOLIC AND
MITOGENIC POTENCY OF IA
HAPO: Hyperglycemia And Adverse Pregnancy O
utcome
• 9 countries, 25 centers, 23,325 patients
• 7 year study
• Women were screened between 24-32weeks with fa
sting glucose, 1 hour and 2 hour post 75 gm glucose
.
• Medical caregivers were blinded to results except th
at exceeded pre defined cut offs[ 5.8 fasting, 11.1 p
ost 75 gm glucose] and were then removed from th
e study.
• Birth weight, maternal complications, operative deli
very, insulin levels in newborn were studied.

Int J,Gynecology & Obstetrics. 2002,78, (1);69-77

 GLYCEMIC STATUS IN GDM

FASTING HYPOGLYCEMIA

POSTPRANDIAL HYPERGLYCEMIA

Normalisation of this is possible by Insulin Analo

gues.
Insulin aspart qualifies for use in GDM
• Insulin analogues does not cross the placenta
but placental concentration is higher than in
maternal blood.
Insulin Aspart in pregnancy status compar
ed with Human Insulin
Moshe Hod et al.,
Studied insulin aspart in Type I diabetic patient
Randomized parallel group open label
Multinational study
- Decreased hypoglycemic spells
- Increased fetal outcome
Insulin Aspart in pregnancy status com
pared with Human Insulin
Primary objective – Hypoglycemic attacks
Secondary objective – Analyze maternal/fetal ou
tcome
- HbA1c
- 8 point glucose profile
- Number of mild hypoglycemia
- cord blood insulin AB
• Mean cord blood insulin level is lower in IA group
 INSULIN TACTICS

Twice-daily Split-mixed Regimens

Regular
NPH
Insulin Effect

B L S HS B

6-2
C
FUTURE CONCEPTS IN INSULIN
THERAPY
Continuous Subcutaneous Insulin Infus
ion (CSII)
• Blood glucose levels monitored continuously
• Pre specified insulin dose is subcutaneously de
livered by pump
• This minimized timing and dosing errors.
Continuous Glucose Monitoring Syste
m (CGMS)
• Blood glucose is assessed periodically
• Insulin dose is calculated
• CGMS integrated monitoring system with a del
ivery device
• Hence round the clock blood glucose is control
led.
 e-health system
• Patient has her data in USB device which can b
e analyzed and seek guidance from internet.
 CSII & CGMS
• Paradigm device connects CGMS and delivery
device through bluetooth. This early trial is ab
out to be started in USA.
THANK YOU