Globally the burden of GDM and hypertension in pregnancy is increasing, and in India too it is 5-15%. Although insulin resistance is a physiological phenomenon in normal pregnancy, in predisposed individuals this could lead to hyperinsulinemia with development of GDM, hypertensive disorders of pregnancy or both Early recognition is the key to prevent feto-maternal complications in these medical disorders

1. Prediction of Gestational Diabetes
Mellitus and Hypertensive Disorders in
Pregnancy using Insulin Resistance at
11-14 weeks of Gestation
A Prospective Observational Study
Dr. Indraneel Jadhav, Dr. Shashikala K Bhat
Dr. TMA Pai Hospital, Udupi
Manipal Academy of Higher Education

2. Introduction
 Globally the burden of GDM and hypertension in pregnancy is increasing, and
in India too it is 5-15%.
 Although insulin resistance is a physiological phenomenon in normal
pregnancy, in predisposed individuals this could lead to hyperinsulinemia
with development of GDM, hypertensive disorders of pregnancy or both
 Early recognition is the key to prevent feto-maternal complications in these
medical disorders

3. Fuel Metabolism in Pregnancy
• ↑ Insulin sensitivity
• ↑ Insulin secretion
• All changes for increased fetal glucose requirement
First and early second trimester
• ↑ Insulin resistance
• ↓ Insulin secretion
• Due to: ↑↑ Diabetogenic hormones secreted by placenta
Late second and early third trimester
Hence, late pregnancy is characterized by:
Fetal growth
Accelerated starvation
Peripheral insulin resistance
(Diabetogenic Hormones : hPL, Prolactin, Cortisol, Estrogen and Progesterone)

4. Insulin Resistance (IR)

5. • Presence of one
 Type 2 Diabetes Mellitus
 High Fasting Glucose
 Insulin Resistance (determined by
any method)
• Presence of two or more
• Hypertension >140 mm of Hg and /or Diastolic
Blood pressure > 90 mm of Hg. and /or
antihypertensive usage
• Hypertriglyceridemia [2 SD for that pregnancy wk ]
• ↓ HDL-Cholesterol [2 SD for that pregnancy wk ]
• Waist/hip ratio >0.85 and or BMI> 30 kg/m
2
WHO Diagnostic Criteria for Metabolic Syndrome during pregnancy
Insulin Resistance (IR)

6. Aim and Objectives
1. Prediction of gestational diabetes mellitus and hypertensive
disorders in pregnancy using insulin resistance at 11-14weeks of
gestation
2. To evaluate if combined maternal markers (insulin resistance and
uterine artery Doppler pulsatility index) in first trimester of
pregnancy (11-14 weeks) is more effective in predicting the same

7. Inclusion and exclusion criteria
• Inclusion criteria :
Antenatal women with singleton pregnancies booked from 1st trimester and willing to deliver
in our hospital
• Exclusion criteria :
• Women with multiple pregnancies
• Women with pre-gestational diabetes
• Women with chronic hypertension
• Women with renal disease
• Smokers or with history of illicit drug use
• Fetus with suspected chromosomal abnormality at NT scan

8. Material & Methods
• Study Site: Dr. TMA Pai Hospital, Udupi, MAHE
• Study Population: Antenatal women booked in Dr. T.M.A Pai Hospital,
Udupi from 1st trimester satisfying inclusion criteria
• Sample Size: Anticipating a sensitivity (p) of 80 %, with precision (d) of
10 % and prevalence of 10% of Gestational Diabetes
Mellitus/Hypertensive disorders of pregnancy, with ratio of 1:3 for the
positives to negatives, sample size was 160
• Study Design: Prospective observational study
• Time Frame: 1 Year (01/12/2015 – 30/11/2016)

9. Material & Methods
• Fasting blood sugar:
Glucose oxidase and peroxidase method by fully Automated Analyzer Hitachi 902
• Fasting insulin:
Specific chemi-luminescence tests
• Insulin resistance by Homeostasis Model Assessment (HOMA) formula:
• Uterine artery Doppler pulsatality index
 Using Philips HD7 machine by a trained sonographer

10. A total of 209 cases were recruited in the study at 11-
14weeks
 2 were excluded from study in view of abortion
 9 women were lost to follow up
 198 were followed up with one step GCT at 24-28weeks
and regular BP monitoring
165 delivered in study period and were analysed for IR
and prediction of GDM/hypertensive disorders
 118 also underwent uterine artery Doppler PI during the
11-14 weeks’ NT scan and were analysed for combined
screening and prediction of GDM/hypertensive disorders
Recruitment-to-analysis flow of the study
Total recruited at 11-14wk
N=209
Excluded
Lost to follow-up (9)
Abortion (2)
N=11
Followed up with GCT and
regular BP monitoring
N=198
Delivered during the study period
N= 165
Analysed with HOMA IR and
Uterine Artery Doppler
N=118

11. HOMA – IR analysis in Present Study
(n= 165)
Sensitivity Specificity
Positive
Predictive value
Negative
Predictive value
1.87 80.5 67.2 44.6 91.3
1.9 78 67.2 43.8 90.3
0
10
20
30
40
50
60
70
80
90
100
Percentage%
Probable cut -off values for HOMA - IR
• Likelihood ratio with taking HOMA – IR cut off as
1.87 was 2.5.
• Hence, in this study HOMA – IR cut off was taken
as 1.87 for further analysis

12. Baseline Characteristics in Present Study
(n= 165)
Age (yrs) Height (cm) Weight (kg) BMI (kg/m2) SBP (mm Hg) DBP (mm Hg) GCT
HOMA -IR < 1.87 27.92 157.08 50.646 20.52 115.34 71.36 104.43
HOMA -IR > 1.87 27.86 156.96 57.82 23.53 116.57 71.57 118.89
P value 0.013 0.139
HOMA - IR with study parameters
(n = 165)
• HOMA –IR values positively correlated with BMI in present study (p value - 0.013)
• Higher HOMA –IR values showed higher one step GCT values but was not statistically significant

13. HOMA – IR Analysis and Obstetrical Outcome
(n=165)
• Positives - developed either GDM/HTN during their pregnancy
25%
75%
GDM/HTN cases
Positives = 41
Negatives = 124
Negatives Positives
HOMA -IR < 1.87 84 9
HOMA -IR > 1.87 40 32
0
10
20
30
40
50
60
70
80
90
HOMA - IR with Obstetrical outcome
(n = 165)
• HOMA- IR values showed 78.5 % diagnostic accuracy in detecting positives

14. HOMA – IR analysis and Obstetrical outcome
(n=165)
HOMA –IR was more effective in detecting GDM (p value - 0.0001)
Gestational HTN GDM IUGR Oligo hydramnios Poly hydramnios
HOMA -IR < 1.87 3 6 6 2 2
HOMA -IR > 1.87 8 26 4 2 0
P value 0.0001
0
5
10
15
20
25
30
Cases
HOMA - IR with specific outcome
(n = 165)

15. Uterine Artery Doppler Analysis in Present Study
(n= 118)
•Likelihood ratio with taking uterine artery Doppler PI
cut off as 1.3 was 1.14 with diagnostic accuracy of
only 55 %.
•Hence, disregarded as a diagnostic parameter in
further analysis
Sensitivity Specificity
Positive Predictive
value
Negative
Predictive value
1.3 78.1 31.4 29.8 79.4
0
10
20
30
40
50
60
70
80
90
Percentage%
Probable cut off value for Uterine artery
Doppler

16. Uterine Artery Doppler in Present Study
(n= 118)
Characteristic Median Inter-quartile range
Right Uterine artery Doppler 1.3 0.9, 1.6
Left Uterine artery Doppler 1.3 1.0 , 1.8
There is a limited role for uterine artery Doppler study in early pregnancy to identify
pregnancies with increased risk of developing hypertensive disorders or GDM
Negatives Positives
Ut doppler < 1.3 27 7
Ut.Doppler >1.3 59 25
0
10
20
30
40
50
60
70
Cases
Ut. Artery Doppler PI with Obstetrical outcome
(n = 118)

17. Combined Uterine artery Doppler and HOMA –IR
(n= 118)
• Likelihood ratio with combined uterine artery Doppler PI cut-off as 1.3 and HOMA –IR
cut-off as 1.87 was 1.4
• Early uterine artery Doppler and HOMA –IR combined may be particularly useful in
identifying most severe spectrum of disease and at risk population
Sensitivity Specificity
Positive
Predictive
value
Negative
Predictive
value
Ut. Doppler -1.3 and HOMA -
IR -1.87
93.8 22.1 30.9 90.5
0
10
20
30
40
50
60
70
80
90
100
Percentage%
Combined Uterine Doppler and HOMA - IR
Negatives Positives
Ut doppler < 1.3 19 2
Ut.Doppler >1.3 67 30
0
10
20
30
40
50
60
70
80
Cases
Combined
(n = 118)

18. Strengths and limitations of study
• First study in India to use insulin resistance in early pregnancy for
prediction of GDM/hypertensive disorders in pregnancy
• As Doppler was not performed for all pregnant women at 11-14
weeks, the combined screening could not be studied adequately.

19. Conclusion
HOMA – IR can be used to predict GDM/Hypertensive disorders of pregnancy at
11-14 weeks gestation with reasonable accuracy
Uterine artery Doppler PI when used alone, is not a useful marker for prediction of
GDM/hypertensive disorder of pregnancy
Combined screening algorithm with HOMA –IR and uterine artery Doppler has
limited role and may help only in select high risk population
The prospect of screen positive women being given low dose aspirin (75mg) and
advice regarding appropriate dietary management to help prevent the
development of hypertensive disorders/GDM in later gestation needs to be
explored by larger trials