Preeclampsia as a Risk Factor for Diabetes

Preeclampsia as a Risk Factor for Diabetes: A PopulationBased Cohort Study
Denice S. Feig1,2,3,4,5*, Baiju R. Shah1,2,3,6, Lorraine L. Lipscombe1,2,3,7, C. Fangyun Wu3, Joel G. Ray1,2,3,8,
Julia Lowe1,6, Jeremiah Hwee3, Gillian L. Booth1,2,3,8,9
1 Department of Medicine, University of Toronto, Toronto, Canada, 2 Department of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada,
3 Institute for Clinical Evaluative Sciences, Toronto, Canada, 4 Department of Obstetrics & Gynecology, University of Toronto, Toronto, Canada, 5 Division of Endocrinology
and Metabolism, Mount Sinai Hospital, Toronto, Canada, 6 Division of Endocrinology and Metabolism, Sunnybrook Health Sciences Centre, Toronto, Canada, 7 Women’s
College Research Institute and the Division of Endocrinology and Metabolism, Women’s College Hospital, Toronto, Canada, 8 Keenan Research Centre, Li Ka Shing
Knowledge Institute, St. Michael’s Hospital, Toronto, Canada, 9 Division of Endocrinology and Metabolism, St. Michael’s Hospital, Toronto, Canada
Abstract
Background: Women with preeclampsia (PEC) and gestational hypertension (GH) exhibit insulin resistance during
pregnancy, independent of obesity and glucose intolerance. Our aim was to determine whether women with PEC or GH
during pregnancy have an increased risk of developing diabetes after pregnancy, and whether the presence of PEC/GH in
addition to gestational diabetes (GDM) increases the risk of future (postpartum) diabetes.
Methods and Findings: We performed a population-based, retrospective cohort study for 1,010,068 pregnant women who
delivered in Ontario, Canada between April 1994 and March 2008. Women were categorized as having PEC alone
(n = 22,933), GH alone (n = 27,605), GDM alone (n = 30,852), GDM+PEC (n = 1,476), GDM+GH (n = 2,100), or none of these
conditions (n = 925,102). Our main outcome was a new diagnosis of diabetes postpartum in the following years, up until
March 2011, based on new records in the Ontario Diabetes Database. The incidence rate of diabetes per 1,000 person-years
was 6.47 for women with PEC and 5.26 for GH compared with 2.81 in women with neither of these conditions. In the
multivariable analysis, both PEC alone (hazard ratio [HR] = 2.08; 95% CI 1.97–2.19) and GH alone (HR = 1.95; 95% CI 1.83–2.07)
were risk factors for subsequent diabetes. Women with GDM alone were at elevated risk of developing diabetes postpartum
(HR = 12.77; 95% CI 12.44–13.10); however, the co–presence of PEC or GH in addition to GDM further elevated this risk
(HR = 15.75; 95% CI 14.52–17.07, and HR = 18.49; 95% CI 17.12–19.96, respectively). Data on obesity were not available.
Conclusions: Women with PEC/GH have a 2-fold increased risk of developing diabetes when followed up to 16.5 years after
pregnancy, even in the absence of GDM. The presence of PEC/GH in the setting of GDM also raised the risk of diabetes
significantly beyond that seen with GDM alone. A history of PEC/GH during pregnancy should alert clinicians to the need for
preventative counseling and more vigilant screening for diabetes.
Please see later in the article for the Editors’ Summary.
Citation: Feig DS, Shah BR, Lipscombe LL, Wu CF, Ray JG, et al. (2013) Preeclampsia as a Risk Factor for Diabetes: A Population-Based Cohort Study. PLoS
Med 10(4): e1001425. doi:10.1371/journal.pmed.1001425
Academic Editor: Philippa Middleton, The University of Adelaide, Australia
Received October 14, 2012; Accepted March 5, 2013; Published April 16, 2013
Copyright: 2013 Feig et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was funded by the Canadian Diabetes Association, grant #OG-2-10-3000-DF (http://www.diabetes.ca/). This study was supported by the
Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. BRS and LL are
supported by Canadian Institute of Health Research New Investigator awards. The funders had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript. The opinions, results, and conclusions reported in this paper are those of the authors and are independent from the
funding sources. No endorsement by ICES or the Ontario Ministry of Health and Long-Term Care is intended or should be inferred.
Competing Interests: The authors have declared that no competing interests exist.
Abbreviations: GDM, gestational diabetes; GH, gestational hypertension; HR, hazard ratio; PEC, preeclampsia.
* E-mail: d.feig@utoronto.ca
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Introduction
The prevalence of type 2 diabetes is increasing dramatically
worldwide [1] with the greatest rise in incidence occurring in
adults under the age of 50, including young women [2].
Randomized trials have shown that type 2 diabetes can be
prevented or delayed in high-risk groups by a variety of lifestyle
and therapeutic interventions [3,4]. However, identifying at risk
populations to screen for type 2 diabetes is a critical step in
translating these findings into clinical practice. Gestational
diabetes is a major risk factor for the development of diabetes
[5] and thus women with this condition are an ideal population to
target diabetes prevention strategies. Similarly, other disorders of
pregnancy associated with insulin resistance may heighten the
propensity for women to develop diabetes in the years following
pregnancy, and such women may also be suitable targets for
diabetes prevention.
Hypertensive disorders in pregnancy, including gestational
hypertension (GH) and preeclampsia (PEC), affect approximately
8% of all pregnancies [6]. More recently, women with PEC/GH
have been noted to exhibit insulin resistance during pregnancy
that is independent of obesity and glucose intolerance [7,8].
Studies done during pregnancy suggest that insulin resistance
predates the development of PEC, implying that insulin resistance
may play a role in its etiology [7,8]. Moreover, women with other
disorders associated with insulin resistance tend to have increased
rates of PEC/GH. For example, several studies have shown that
women with gestational diabetes mellitus (GDM) have an
increased risk of PEC/GH [9,10], as do women with polycystic
ovary syndrome [11]. The risk of PEC/GH also increases with
increasing glucose intolerance [10,12,13].
Given the finding of insulin resistance in women with PEC/GH,
and the association of PEC/GH with other disorders associated
with insulin resistance in pregnancy, these conditions may be a
marker of future diabetes risk, even in the absence of GDM. A few
studies have looked at this association but have failed to take into
account the presence of GDM. This study sought to examine
whether women with PEC or GH during pregnancy have an
increased risk of developing diabetes in the years following
pregnancy even in the absence of GDM, and to determine
whether the combination of PEC/GH and GDM confers a greater
risk of postpartum diabetes, over and above the risk seen with
GDM alone.
Methods
Ethics Statement
This protocol received ethical approval from the Institutional
Review Board at Sunnybrook Health Sciences Centre in Toronto.
Data Sources
We conducted a population-based cohort study using administrative health claims to examine the impact of PEC/GH on the
subsequent risk of diabetes. The Government of Ontario acts as a
single payer for all medically necessary services across a full
spectrum of providers and hospitals to provide all residents of
Ontario (approximately 12 million residents) with universal public
health insurance. Large provincial health administrative databases
are used to capture the details of this utilization and can be linked
anonymously on an individual level using a unique personal
identifier to provide a complete health services use profile for each
resident.
Study Population and Eligibility
We identified all women age 15 to 50 y of age who delivered in
an Ontario hospital between April 1, 1994 and March 31, 2008
from the Canadian Institute for Health Information Discharge
Abstract Database. For women who had multiple deliveries during
the time period, one delivery was chosen at random to be the
index episode from which they were followed forward in time.
Women with a diagnosis of diabetes before their pregnancy were
identified and excluded from the study using the Ontario Diabetes
Database [14], an administrative data derived registry of Ontario
residents diagnosed with non-gestational diabetes. The database
has been validated against primary care charts and was shown to
have a sensitivity of 86% and a specificity of greater than 97%
[14]. We restricted the cohort to women who were residents of
Ontario and had coverage under the province’s health plan for a
full 2 y prior to baseline so that we could reliably determine their
diabetes status.
Women in our cohort were categorized as having PEC, GH, or
GDM on the basis of their hospitalization records and outpatient
data from physicians’ services claims. Women who were diagnosed
with both PEC and GH were assigned to the PEC group. Women
assigned to the GH group had GH alone. Women whose
hospitalization record at the time of delivery included a diagnostic
code for diabetes or who had three or more outpatient medical
claims for diabetes up to 120 d prior to their delivery were
identified as having GDM. Women were considered to have a
premature delivery if the delivery was ,37 wk gestation.
Baseline Variables and Study Outcomes
Women in our cohort were followed from 180 d post delivery
(to avoid the potential misclassification of women with GDM
undergoing routine postpartum follow-up) until March 31, 2011
for the development of diabetes, on the basis of the presence of a
new record in the Ontario Diabetes Database.
We gathered demographic and clinical characteristics from
administrative data to be applied in our adjusted multivariable
models (see Text S1 for codes used). The age of the women was
obtained through the Registered Persons Database, which
contains demographic and residential information on all residents
of Ontario. The Johns Hopkins Adjusted Clinical Groups (ACG)
System [15] was used to create separate case-mix categories
(known as collapsed ambulatory diagnostic groups [CADGs]) that
reflect an individual’s underlying level of morbidity. These groups
were created using diagnostic codes from hospitalization records
and physicians’ services claims from the period 2 y prior to but
excluding the delivery date. This system is a widely used method
for case-mix adjustment and correlates well with health care
utilization. The stable chronic medical category includes a variety
of chronic conditions such as hypercholesterolemia, mitral valve
disorders, atrioventricular block, and simple chronic bronchitis.
The unstable chronic disease includes such conditions as ischemic
heart disease, chronic obstructive lung disease, chronic liver
disease, chronic kidney disease, and malignancy, among others
(see Table S1 for a listing of all categories). Diagnostic codes for
diabetes and hypertension were not included in the creation of the
case-mix categories. Hypertension prior to pregnancy was assessed
using the Ontario Hypertension Database, a validated database
that identifies all individuals in Ontario who have been diagnosed
with hypertension with sensitivity of 73% and a specificity of 95%
[16]. For the purpose of our study, a woman was identified to have
prior hypertension if the diagnosis date was greater than 280 d
before the delivery. Women found to be in the Hypertension
Database and diagnosed with GH were removed from the cohort,
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as women, by definition, cannot have GH and have hypertension
prior to pregnancy. Information on individual-level income was
not available in our data sources; therefore, neighborhood
characteristics derived from the Canadian census were used as a
proxy. The median household income level of each woman’s
neighborhood of residence was attributed to them using their
postal code at the time of their delivery. Baseline parity was only
available for a subgroup of women in our cohort who delivered
between April 1, 2002 and March 31, 2008, therefore a sensitivity
analysis was performed in this subset to assess the influence of
parity on the association between PEC and diabetes incidence. To
test whether the severity of PEC modified the association between
PEC and diabetes incidence, we stratified our population of
women with this condition (with or without concomitant GDM)
on the basis of whether or not they had a premature delivery.
Statistical Analysis
We calculated descriptive statistics and used one-way ANOVA,
the Kruskal–Wallis test, and the chi-square test to compare the
baseline characteristics of women in our different exposure groups.
Incidence rates were expressed on the basis of the number of new
cases of diabetes per 1,000 person-years of follow-up. A Cox
proportional hazards model was used to examine the impact of
PEC, GH, or GDM (with or without concomitant PEC or GH) on
the risk of developing diabetes. Women were censored when
follow-up was terminated; this happened at the time of death, loss
of health care coverage if the women moved out of the province, if
they experienced an outcome event, or at the end of the
observation window. The covariates included in our model were
age, socioeconomic status, hypertension (prior to pregnancy), comorbidity, and parity (for the subset of women for whom it was
available).
The proportional hazards assumption was tested [17], and
interaction terms using a time-dependent covariate were inserted
into the model in a second sensitivity analysis. Parity was felt to be
an important covariate but was only available after 2002. For this
reason a sensitivity analysis was done to assess the influence of
parity on the risk of development of diabetes during the period
after 2002. Women with PEC who deliver early are considered to
have more severe PEC. Using PEC along with preterm delivery as
a proxy for PEC severity, we performed a sub-analysis. Number
needed to follow was also calculated among a random sample of
100,000 women [18]. The analyses were done using SAS version
9?2 (SAS Institute Inc).
Results
A total of 1,709,019 deliveries were captured in Ontario from
April 1994 to March 2008. Among those that were excluded from
the study, 1.3% had pregestational diabetes. A further 7.3% were
excluded because they were not Ontario residents or lacked
coverage under Ontario’s Health Insurance Plan for a full 2 y
prior to delivery (see Figure 1). Among the 1,010,068 pregnant
women available for analysis, 22,933 cases of PEC alone, 27,605
cases of GH alone, 30,852 cases of GDM alone, 2,100 cases of
GDM+GH, and 1,476 cases of GDM+PEC were identified. The
range of follow-up was 1 d to 16.5 y, with a median follow-up of
8.5 y. Overall 35,077 women developed diabetes (3.5%).
Demographic and clinical characteristics of women included in
the study, stratified by their PEC, GH, and GDM status is
presented in Table 1. Women with GDM tended to be older and
were more often in the lowest income quintile. Previous
hypertension was more common in women with GH or PEC
than women without either, particularly if they had concomitant
GDM. The level of co-morbidity was low across all groups but
somewhat higher in those with GDM+GH and GDM+PEC
compared to women without these conditions.
The unadjusted cumulative incidence of diabetes, stratified by
GDM, GH, and PEC status, is presented in Figure 2. Among
women in our cohort, both PEC and GH were associated with an
elevated cumulative probability of developing diabetes. Women
with GDM had an even higher cumulative probability of
developing diabetes but this appeared to be heightened by the
co-presence of PEC or GH.
The incidence rate of diabetes per 1,000 person-years is
illustrated in Table 2. Women with GH or PEC had higher
incidence rates of diabetes than those without either (5.26 per
1,000 person-years, 6.47 per 1,000 person-years, and 2.81 per
1,000 person-years, respectively). Those with GDM had a much
higher incidence rate than those without GDM. Women with
GDM and either PEC or GH had a higher incidence rate than
Figure 1. Cohort flow chart illustrating the inclusion and exclusion of participants into the study. *Mothers either lacked coverage under
Ontario’s Health Insurance Plan at the admission delivery date or had health insurance for less than 2 y prior to their delivery.
doi:10.1371/journal.pmed.1001425.g001
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women with GDM alone (55.02 per 1,000 person-years, 55.09 per
1,000 person-years versus 39.77 per 1,000 person-years, respectively). The mean age at diagnosis of diabetes overall was 37.34,
with a median age of 37.0. The number needed to follow for 5 y to
detect one case of diabetes was 4,511 for GH alone, 123 for PEC
alone, 68 for GDM alone, 105 for GDM+GH, and 31 for
GDM+PEC (see Table 3).
In the unadjusted Cox proportional hazards model, women
who had GH or PEC during pregnancy had double the risk of
developing diabetes in the 16.5 y following delivery, compared to
women who had neither during pregnancy (Table 2). Women with
GDM had a 15-fold increased rate of developing diabetes over
those without GDM, PEC, or GH, while women with GDM+PEC
and GDM+GH during pregnancy had the highest rates with a 20-
to 21-fold increased rate. These effects were only modestly
reduced after adjusting for age, income quintile, hypertension
prior to pregnancy, and co-morbidity, (hazard ratio [HR] 1.95
[1.83–2.07] for GH alone, HR 2.08 [1.97–2.19] for PEC alone,
HR 12.77 [12.44–13.10] for GDM alone, HR 18.49 [17.12–
19.96] for GDM+GH, HR 15.75 [14.52–17.07] for GDM+PEC)
(Table 2). See Table S2 for the number of women at risk at the end
of each follow-up year.
A sensitivity analysis was done to assess the influence of parity
on the risk of development of diabetes using data from 2002–2008.
The association between future DM and GH/PEC and GDM
became even stronger when adjusting for parity (along with age,
income quintile, prior hypertension, and co-morbidity) (HR for
GH alone 1.82 [95% CI 1.63–2.03], HR for PEC alone 1.92 [95%
CI 1.63–2.28], HR for GDM alone 16.56 [95% CI 15?81–17.34],
HR for GDM+GH 23.48 [21.01–26.24], HR for GDM+PEC
22.53 [18.54–27.38]).
In the second sensitivity analysis, a time-dependent covariate
was added into the adjusted model as an interaction term. There
was a time-varying effect among the groups on the risk of
developing diabetes, especially those with GDM. The risk for
developing diabetes in women with GH and PEC stayed fairly
stable at the 2-y, and median follow-up times (GH HR = 1.99 for
all times; PEC HR = 2.26 and HR = 2.01, respectively). For those
with GDM, however, the risk of developing diabetes decreased
over time compared with the women without GH/PEC or GDM
(HR = 19.09 at 2 y, HR = 8.20, at median follow-up of 8.5 y).
Similar patterns were seen in the GDM+GH and the GDM+PEC
groups (HR = 25.28, HR = 12.86; and HR = 24.54, HR = 11.13,
at 2 and 8.5 y, respectively).
A sub-analysis was performed looking at PEC severity by
assessing PEC along with preterm delivery. There was a trend
towards a greater incidence of diabetes among women with PEC
who had a preterm delivery (Figure 3). Those women with GDM
and PEC and preterm delivery experienced the highest risk of
developing diabetes, HR 30.73 (95% CI 23.73–39.78) (Figure 3).
Discussion
In this study the presence of PEC or GH, in the absence of
GDM, was associated with a 2-fold increased incidence of diabetes
when followed up to 16.5 years after pregnancy, after controlling
for several important confounding variables. In the setting of
GDM, these conditions were associated with a further elevation in
diabetes risk, over and above the already substantial (,13-fold)
increase resulting from GDM alone. This risk was even higher in
the setting of preterm delivery, suggesting that diabetes incidence
rises with increasing severity of these hypertensive disorders. These
findings highlight a possible new risk factor for diabetes, and
support the need to counsel patients with hypertensive disorders of
pregnancy regarding postpartum diabetes screening prevention.
Common pathogenic pathways may underlie the association
between both GDM and PEC/GH leading to an increased risk of
diabetes. Firstly, each of these conditions is associated with insulin
resistance [7,8,11,19,20]. Not only do women with PEC/GH have
insulin resistance during pregnancy, several studies have also
found higher levels of insulin resistance in women with a history of
PEC/GH years after delivery, even after controlling for body mass
index and excluding women with previous GDM [21,22]. Women
with a history of PEC/GH also show manifestations of the

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metabolic syndrome years after delivery, a syndrome known for its
association with insulin resistance [23–26]. Endothelial dysfunction and markers of chronic vascular inflammation have been
found in women with PEC as well as women with GDM, both
during and after pregnancy [27–30]. These entities have been
shown to precede the development of overt hyperglycemia in
patients at risk for type 2 diabetes [30]. We hypothesize that these
common mediators are likely to increase the risk of type 2 diabetes
in women with a history of PEC.
We found that the risk of developing diabetes over the years was
stable for those with GH and PEC alone; however, the risk
decreased over time in women with GDM. It may be that those with
a very high risk develop diabetes early on. Those who remain have
an inherently lower risk leading to the lower HR ratio observed.
This finding is consistent with what we know about the natural
history of diabetes postpartum. Some groups develop diabetes at a
very high rate early on (50% within 5 y of delivery) [31].
Three previous studies looked at the risk of developing type 2
diabetes in women with a history of PEC/GH. In one study,
women enrolled in the Mater–University of Queensland Study of
Pregnancy between 1981 and 1984 who had PEC/GH at baseline
were 1.76 times more likely to report having developing diabetes
21 y later [32]. However, approximately one-half of their original
cohort were lost to follow-up. In a Danish cohort of women with
PEC or GH, the risk of diabetes postpartum was also found to be
increased over a median of 14.6 years [33]. Neither of these
preceding studies were able to isolate the risk imparted by PEC/
GH from that of GDM. A third registry study of women with PEC
in Norway also found an increased risk of diabetes in women with
PEC, however follow-up was short, only 3.7 y, and the diagnosis of
diabetes was made in women using medications for diabetes,
possibly under-estimating the true incidence of diabetes [34].
Strengths of our study include that this study was a large,
population-based study with long and complete follow-up (over
Figure 2. Cumulative future risk of diabetes mellitus in association with a pregnancy affected by preeclampsia, gestational
hypertension, and gestational diabetes. *Follow-up period begins 180 d postpartum. This figure was produced using a competing risk method.
doi:10.1371/journal.pmed.1001425.g002

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1,000,000 women followed for up to 16.5 y). Our study also
examined the risk of diabetes associated with both GH and PEC,
while controlling for the presence of GDM, and examined the
combined impact of GDM and PEC/GH together. We were also
able to examine the severity of PEC with the addition of preterm
delivery. Some limitations of this study include our inability to
adjust for clinical factors, in particular, obesity, which in itself is
associated with insulin resistance, and is a well-known risk factor
for the development of GDM [35] and PEC [36]. Obesity is not
well captured in our inpatient hospitalization database, nor is it
well coded in our outpatient database, which is based on physician
outpatient billing codes. Furthermore, family history, physical
activity, glucose, and blood pressure measures are also known risk
factors. We were, however, able to adjust for several other
important confounding variables including maternal age, prior
hypertension, income quintile, parity, and co-morbidity. One
previous study was able to adjust for obesity and physical activity,
and the risk of developing diabetes was still significant [30]. From
our data sources we could not differentiate type 1 from type 2
diabetes; however, given the mean age at diagnosis was 37.4 y, it is
most likely that the majority of the women developed type 2
diabetes in the years after pregnancy. Women with a history of
GDM may be offered routine glucose testing postpartum, thus
leading to more diagnoses of diabetes compared with women with
a history of PEC. This situation may have led to under-reporting
of diabetes in women with a history of PEC; therefore the rate of
development of diabetes in these women may even be higher than
reported. Follow-up of women with hypertensive disease in
pregnancy may lead to more interactions with the health care
system compared to women without hypertensive diseases in
pregnancy, thus leading to more diabetes testing and diagnosis and
a possible bias towards overestimating the risk; however, there is
currently no standard recommendation to screen women with
GH/PEC for diabetes postpartum. Our capture of GH and PEC
may have been incomplete. In a study looking at the accuracy of
hospital data in the perinatal period using ICD-10 codes, when
diagnosing GH and PEC, sensitivity was reduced (58.6% and
50.0%, respectively), however specificity was excellent (99% and
99.8%, respectively) [37]. Finally, the algorithms used to describe
a number of the variables used in the study (GDM, PEC, GH)
have not been formally validated.

Figure 3. Sub-analysis modeling the relationship among preeclampsia, gestational hypertension, gestational diabetes, and
preterm delivery in the development of diabetes. Model also adjusts for age, income quintile, prior hypertension, and co-morbidity using the
Johns Hopkins collapsed ambulatory diagnostic group (CADG). The bands represent 95% confidence intervals.
doi:10.1371/journal.pmed.1001425.g003
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In summary, in this large, population-based study, we found
that the presence of either PEC or GH during pregnancy were
strong predictors for the development of diabetes years following
the pregnancy, and the presence of PEC or GH in a woman with a
history of GDM increased the risk of diabetes over and above that
observed with GDM alone. These findings have important
implications for maternal health, especially given the increase in
obesity-related diseases. A history of PEC or GH during
pregnancy should alert clinicians to the need for preventative
counseling and more vigilant screening for diabetes.
Supporting Information
Table S1 Distribution of co-morbidity categories (collapsed
ambulatory diagnostic groups)* among women stratified by
gestational diabetes diagnosis. *Collapsed ambulatory diagnostic
groups [CADGs] were created using the Johns Hopkins Adjusted
Clinical Groups (ACG) System. CADG category number 12
(pregnancy) was not included in the analyses.
(DOCX)
Table S2 Number of women at risk at the end of each follow-up
year in Ontario, from 1994 to 2011. *Year 0 indicates the
beginning of the follow-up period.
(DOCX)

Acknowledgments
We thank Charles Victor for his invaluable assistance with analysis and
interpretation of data.
Author Contributions
Conceived and designed the experiments: DSF BS LL JR JL GB.
Performed the experiments: FW. Analyzed the data: DSF BRS LLL FW
JGR JH GLB. Wrote the first draft of the manuscript: DSF. Contributed to
the writing of the manuscript: DSF BRS LLL FW JGR JL JH GLB.
ICMJE criteria for authorship read and met: DSF BRS LLL FW JGR JL
JH GLB. Agree with manuscript results and conclusions: DSF BRS LLL
FW JGR JL JH GLB.
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Preeclampsia and Future Risk of Diabetes
PLOS Medicine | www.plosmedicine.org 7 April 2013 | Volume 10 | Issue 4 | e1001425
Editors’ Summary
Background. Diabetes is a chronic disease that occurs
either when the pancreas does not produce enough insulin
(a hormone that regulates blood sugar), known as type 1
diabetes, or when the body cannot effectively use the insulin
it produces—type 2 diabetes. Raised blood sugar, is a
common effect of uncontrolled diabetes and over time leads
to serious complications and even death. Worryingly, the
global burden of type 2 diabetes is increasing worldwide,
and the World Health Organization estimates that 90% of the
347 million people with diabetes currently have type 2
diabetes. Previous studies have shown that type 2 diabetes
can be prevented or delayed in high risk groups by a range
of lifestyle and treatment interventions and so it is important
to identify potential high risk groups to screen for type 2
diabetes.
Why Was This Study Done? Gestational diabetes (a form
of diabetes that is related to pregnancy) is a major risk factor
for developing type 2 diabetes. Therefore, diabetes prevention strategies should target women with gestational
diabetes. Likewise, other common disorders of pregnancy
possibly associated with insulin resistance, such as preeclampsia (a condition in which affected women have high
blood pressure, fluid retention, and protein in their urine)
and gestational hypertension (high blood pressure associated with pregnancy), may lead to the future development of
type 2 diabetes. So women with these conditions may also
benefit from diabetes prevention strategies. Therefore, in
this large database study from Ontario, Canada, the
researchers examined whether pregnant women with
preeclampsia or gestational hypertension had an increased
risk of developing diabetes in the years following pregnancy
even if they did not have gestational diabetes.
What Did the Researchers Do and Find? The researchers
used a comprehensive Canadian health database to identify
all women age 15 to 50 years of age who delivered in an
Ontario hospital between April 1994 and March 2008. They
then identified women who had preeclampsia, gestational
hypertension, or gestational diabetes through hospital
records and outpatient information. The researchers then
used records from the Ontario Diabetes Database to record
whether these women went on to develop diabetes in the
period from 180 days after delivery until March 2011.
Using these methods, the researchers identified 1,010,068
pregnant women suitable for analysis, of whom 22,933 had
only preeclampsia, 27,605 had only gestational hypertension,
and 30,852 had only gestational diabetes: 2,100 women had
both gestational diabetes and gestational hypertension and
1,476 women had gestational diabetes and preeclampsia.
Overall, 35,077 women developed diabetes (3.5%) in the
follow-up period (median of 8.5 years) at a median age of 37
years. In a modeling analysis, the researchers found that
women with gestational diabetes had a 15-fold increased
rate of developing diabetes compared to women without
gestational diabetes, gestational hypertension, and preeclampsia, while women with gestational diabetes plus
either preeclampsia or gestational hypertension had a 20- to
21-fold increased rate. These results were slightly reduced
after adjusting for age, income quintile, hypertension prior to
pregnancy, and co-morbidity, giving a hazard ratio (HR) of
1.95 for gestational hypertension alone, an HR of 2.08 for
preeclampsia alone, an HR of 12.77 for gestational diabetes
alone, an HR of 18.49 for gestational diabetes plus
gestational hypertension and finally, an HR of 15.75 for
gestational diabetes plus preeclampsia.
These Findings Mean? These findings suggest that both
preeclampsia and gestational hypertension without gestational diabetes are associated with a 2-fold increased
incidence of diabetes in the years following pregnancy after
controlling for several important variables. When combined
with gestational diabetes, these conditions were associated
with a further elevation in diabetes incidence additional to
the 13-fold increased incidence resulting from gestational
diabetes alone. A limitation of this study was the lack of
information on obesity and body mass index, factors which
are also associated with increased risk of developing
diabetes. Nevertheless, these findings highlight a possible
new risk factor for diabetes, and suggest that clinicians
should be aware of the need for preventative measures and
vigilant screening for diabetes in women with a history of
preeclampsia or gestational hypertension.
Additional Information. Please access these Web sites via
the online version of this summary at http://dx.doi.org/10.
1371/journal.pmed.1001425.
N NHS Choices has information about preeclampsia, gestational diabetes, and gestational hypertension
N Living with diabetes is a useful resource for patients with
diabetes
N The Preeclampsia Foundation has more information about
preeclampsia
Preeclampsia and Future Risk of Diabetes
PLOS Medicine | www.plosmedicine.org 8 April 2013 | Volume 10 | Issue 4 | e1001425