1. Preeclampsia and risk of Diabetes in Indian Women
Sutapa Agrawal
Epidemiologist
Centre for Control of Chronic Conditions
Public Health Foundation of India
New Delhi NCR, India

2. Introduction
Preeclampsia, a life threatening common multisystem pregnancy disorder that typically starts after 20th week of pregnancy
is related to increased blood pressure (BP ≥140/90 mmHg) and protein in mother’s urine (urinary albumin protein ≥ 300 mg/24 h)
Preeclampsia, the hypertensive disorders of pregnancy either alone or superimposed on preexisting hypertension
affects around 3 – 5% of pregnancies in developed countries and up to 7.5% pregnancies worldwide
As of 2013, pre-eclampsia remains one of the most important causes of maternal and fetal morbidity and mortality all over the world

3. Introduction
Epidemiological data from high income countries suggests that
women with preeclampsia are more likely to develop cardiovascular disease (risk is two to four times higher) later in life
Women with preeclampsia have been noted to exhibit insulin resistance during pregnancy
which predates the development of diabetes
The risk of preeclampsia also increases with increasing glucose intolerance
which may be a marker of future diabetes risk
The American Heart Association guidelines in 2011 thus recognized
pre-eclampsia and gestation hypertension as independent gender-specific cardiovascular risk factors

4. The context
India is in the midst of a demographic, epidemiological and nutrition transition
characterized by a growing population, increasing urbanisation, a shift in the patterns of diseases and changes in lifestyle
The past decade has seen a dramatic increase in lifestyle related non-communicable diseases
Given that preeclampsia shares many risk factors with cardiovascular disease
the increase in cardiovascular disease risk factors in women in the child bearing age will translate into a higher incidence of preeclampsia
There has not been any previous large-scale report
concerning the association of preeclampsia with diabetes risk in Indian women

5. Objectives
To examine the association between preeclampsia and diabetes risk in a large nationally representative sample of Indian women

6. Data and Methods
Cross-sectional data from India’s third National Family Health Survey (NFHS-3, )
To examine the association between preeclampsia and risk of diabetes
we restricted the sample to only those women who had a live birth in the five years preceding the survey
We further restricted our analyses to data pertaining to the most recent birth to minimize recall bias
This resulted in a final sample size of 39,657 participants

7. Outcome evaluation Current diabetes status was self-reported
The survey asked participants the question, ‘Do you currently have diabetes?’ with the response options of ‘yes’, ‘no’ and ‘don’t know’
However, neither data on physician-reported diagnosis of diabetes or fasting blood glucose was available in the NFHS-3 to verify a self-report

8. Assessment of preeclampsia symptoms
Self-reported symptoms suggestive of pre-eclampsia were obtained from 39,657 women age years who had a live birth in the preceding five years
In NFHS-3, mothers were specifically asked: “During this pregnancy, did you have difficulty with your vision during daylight?”, “During this pregnancy, did you have swelling of the legs, body or face?” The response options were “Yes”, “No”, and “Don’t know”

9. Assessment of preeclampsia symptoms
According WHO (2000) and NICE (2010) Guidelines ,
women who reported difficulty with vision during daylight, and swelling of the legs, body, or face, were coded as having symptoms of pre-eclampsia in this study
However, it was not possible to confirm clinical diagnosis of these symptoms
Data on blood pressure and proteinuria during pregnancy, which are typical clinical diagnostic markers of preeclampsia
were not available in the NFHS-3

10. Covariates
Diversified Dietary intake, often used as a proxy for dietary intake is measured in accordance to WHO criteria with slight modification having a dichotomous category: adequate and inadequate
Body Mass Index categories: underweight, normal, overweight, obese
Current tobacco smoking: no, yes
Current alcohol drinking: no, yes
Frequency of TV viewing: Not at all, less than once a week, at least once a week, almost everyday
Access to healthcare: Public Medical sector, NGO or Trust or Clinic Private Medical Sector, Other source
Socioeconomic characteristics: age, education, employment status, religion, caste/tribe, household wealth index, rural/urban residence, and geographic regions

11. Statistical Analysis
Descriptive statistics were calculated with the use of standard methods
Differences in categorical variables were tested using Pearson’s χ2 tests
A p-value of <0.05 was considered statistically significant
Multivariable logistic regression analysis was restored
in unadjusted, partially adjusted and fully adjusted models
Multivariable models were adjusted
for the above described health and lifestyle factors and socio-demographic characteristics of the woman
In all analyses sample weight was used to restore the representativeness of the sample
All analyses were conducted using the SPSS statistical software package Version 19

12. Results
Overall, 28.7% (n=11,361) women reported symptoms suggestive of preeclampsia during their last pregnancy
1.3% (n=512) women reported diabetes currently
The prevalence of symptoms suggestive of pre-eclampsia in women with diabetes was 1.8% (95%CI: ) compared with 1.1% (95%CI: ) in women with no pre-eclampsia symptoms
In the multivariable analysis, preeclampsia was associated with 1.6 times (OR: 1.68; 95%CI: ; p<0.0001) higher risk for diabetes even after controlling for diversified dietary intake and body mass index

13. Results
In the unadjusted analysis, the likelihood of having diabetes was significantly higher
among women who reported preeclampsia symptoms (OR: 1.71; 95% CI: ; p<0.0001) than those who did not reported a preeclampsia symptoms
Controlling for diversified dietary intake and body mass index slightly attenuated (OR:1.65; 95% CI: ; p<0.0001)
the positive relationship between preeclampsia symptoms and diabetes
The positive association between preeclampsia symptoms and diabetes remained virtually unchanged (OR: 1.73; 95% CI: )
when current tobacco smoking, alcohol drinking, frequency of TV viewing and access to healthcare were additionally controlled
Jointly controlling for all of these factors and socio-demographic characteristics, the positive association (OR: 1.68; 95%CI: )
between symptoms suggestive of preeclampsia during pregnancy and diabetes remains strong and statistically significant in the fully adjusted analysis

14. Main Findings
We examined the association between symptoms suggestive of preeclampsia during pregnancy and diabetes risk
in a large, nationally representative sample of Indian women
The symptoms of preeclampsia during pregnancy, was associated with almost a 2-fold increased likelihood of having diabetes
even after controlling for several important confounding variables
These findings highlight a possible new risk factor for diabetes in developing country as well and
support the need to counsel patients with hypertensive disorders during pregnancy regarding postpartum diabetes screening prevention

15. The possible pathway
Common pathogenic pathways may underlie the association between preeclampsia and diabetes
Not only do women with preeclampsia have insulin resistance during pregnancy, several studies have also found higher levels of insulin resistance in women with a history of preeclampsia years after delivery
even after controlling for body mass index and excluding women with previous gestational diabetes mellitus
Women with a history of preeclampsia also show manifestations of the metabolic syndrome years after delivery, a syndrome known for its association with insulin resistance

16. The possible pathway
Other possible explanations for this association may be the following
both cardiovascular disease and preeclampsia share common risk factors including dyslipidemia, increased insulin resistance, hypertension, obesity, and endothelial dysfunction, turning pregnancy into a “stress test” with the development of hypertensive disorders during pregnancy identifying a woman destined to develop cardiovascular disease (Staff and Redman 2014)
pregnancy, and especially preeclampsia, may induce permanent arterial changes—the proatherogenic stress of pregnancy, excessive in many women with preeclampsia, could activate arterial wall inflammation that fails to resolve after delivery, increasing the risk for future cardiovascular disease (Chen et al 2014)
Staff AC, Redman CW. IFPA award in placentology lecture: preeclampsia, the decidual battleground and future maternal cardiovascular disease, Placenta 2014; 35(supplement): S26–S31.
Chen CW, Jaffe IZ, Karumanchi SA. Pre-eclampsia and cardiovascular disease, Cardiovascular Research, 2014; 101 (4): 579–586.

17. Strengths of the study
To our knowledge, this is the largest nationally representative cross-sectional study of the population based association between preeclampsia symptoms and diabetes risk in an Asian population
We could adjust for obesity, which in itself is associated with insulin resistance, and is a well-known risk factor for the development of diabetes and preeclampsia

18. Limitations
Most variables in the analyses (with the exception of anthropometrics) were self-reported, including a symptomatic rather than clinical measure of preeclampsia and diabetes; it is possible that self-reported data may suffer from recall bias
Due to the nature of the data, we could not identify the gestational onset of preeclampsia
Family history, physical activity, glucose, and blood pressure measures the other known risk factors for diabetes were not collected in the survey
Non-differentiation between type 1 from type 2 diabetes; however, given the mean age of the women was 26.4 y (±5.6SD), it is most likely that the majority of the women developed type 2 diabetes

19. Conclusions
This study provides first empirical evidence that there is a strong association between symptoms suggestive of preeclampsia during pregnancy and diabetes risk
in a large nationally representative sample of Indian women
These findings have important implications for maternal and child health
especially given the increase in obesity-related diseases in this low resource settings
A history of preeclampsia during pregnancy should therefore alert clinicians to the need for preventative counseling and more vigilant screening for diabetes
women should be encouraged to have a more rigorous follow-up and adopt a healthier lifestyle

20. Conclusions
Future studies should focus on strategies to prevent the progression of cardiovascular disease in women exposed to preeclampsia, thereby improving long-term cardiovascular health in women
Further research to verify accuracy of reporting of symptoms of preeclampsia is needed in Indian setting

21. Thank you !