Gestational diabetes mellitus (GDM)
is a common condition affecting
2–4% of pregnant women (1) and
is associated with adverse outcomes for
both the fetus and the mother. Previous
GDM is a major risk factor for type 2 diabetes,
which occurs in 20–60% of affected
women within 5 years of the
pregnancy (2). Women with a history of
GDM are also at increased risk of other
cardiovascular risk factors, such as obesity,
hypertension, dyslipidemia, and the
metabolic syndrome (3–5), as well as subclinical
atherosclerosis (6). Taken together,
these findings suggest that GDM
identifies a population of young women at
increased risk for cardiovascular disease
(CVD). We used population-based administrative
data to determine whether women
with GDM have a heightened risk for CVD
compared with women without GDM and
whether any increase in risk is independent
of subsequent type 2 diabetes.
RESEARCH DESIGN AND
METHODS— We conducted a population-
based retrospective cohort study
using administrative databases from Ontario,
Canada, that included hospital discharge
abstracts, physician service claims,
and demographic data. The Ontario Diabetes
Database is a validated registry of
physician-diagnosed nongestational diabetes
that is identified using these administrative
data (7). Individuals are linked
between all data sources via a unique
health card number, which is reproducibly
encrypted in all of these data sources.
Women aged 20–49 years who had a
hospitalization record indicating a live
birth between April 1994 and March
1997 were selected. For women who had
more than one birth during this period,
one birth was selected at random. Those
who had pregestational diabetes or a CVD
event (as defined below) in the prior 3
years were excluded.
Baseline characteristics were age at
delivery, region of residence, and socioeconomic
status (measured as the neighborhood
income quintile). Subjects with
missing data were excluded. Women
were defined as having GDM using an algorithm
analogous to that used by the validated
registry to exclude GDM: one
hospitalization record or two ambulatory
physician claims bearing the diagnosis of
diabetes or GDM between 120 days before
and 180 days after delivery.
The primary outcome (CVD events)
was defined as a hospitalization for acute
myocardial infarction, stroke, coronary
artery bypass, coronary angioplasty, or
carotid endarterectomy. The prespecified
secondary outcome (coronary artery disease
[CAD] events) was hospitalization
for acute myocardial infarction, coronary
artery bypass, or coronary angioplasty.
Subsequent diagnosis with diabetes was
identified if the woman entered the diabetes
registry postpartum. Although the
registry does not distinguish between
types, the majority of women developing
diabetes in this group would have type 2
diabetes. All women were followed until
March 2007, with censoring on death.
Subjects with GDM were matched
with 10 subjects without GDM based on
baseline characteristics. Kaplan-Meier
survival curves were constructed for both
outcomes. Cox proportional hazards regression
was used to model the association
of GDM with each outcome,
accounting for the matched design of the
study. For each outcome, an unadjusted
model and a model adjusting for subsequent
diagnosis of diabetes as a timedependent
covariate were built. The
assumption of proportionality was verified
by plotting log(–log[survival]) versus
log(time) to assess parallelism. The study
was approved by the institutional review
board of Sunnybrook Health Sciences
Centre.
Gestational diabetes mellitus (GDM)is a common condition affecting2–4% of pregnant women (1) andis associated with adverse outcomes forboth the fetus and the mother. PreviousGDM is a major risk factor for type 2 diabetes,which occurs in 20–60% of affectedwomen within 5 years of thepregnancy (2). Women with a history ofGDM are also at increased risk of othercardiovascular risk factors, such as obesity,hypertension, dyslipidemia, and themetabolic syndrome (3–5), as well as subclinicalatherosclerosis (6). Taken together,these findings suggest that GDMidentifies a population of young women atincreased risk for cardiovascular disease(CVD). We used population-based administrativedata to determine whether womenwith GDM have a heightened risk for CVDcompared with women without GDM andwhether any increase in risk is independentof subsequent type 2 diabetes.RESEARCH DESIGN ANDMETHODS— We conducted a population-based retrospective cohort studyusing administrative databases from Ontario,Canada, that included hospital dischargeabstracts, physician service claims,and demographic data. The Ontario DiabetesDatabase is a validated registry ofphysician-diagnosed nongestational diabetesthat is identified using these administrativedata (7). Individuals are linkedbetween all data sources via a uniquehealth card number, which is reproduciblyencrypted in all of these data sources.Women aged 20–49 years who had ahospitalization record indicating a livebirth between April 1994 and March1997 were selected. For women who hadmore than one birth during this period,one birth was selected at random. Thosewho had pregestational diabetes or a CVDevent (as defined below) in the prior 3years were excluded.Baseline characteristics were age atdelivery, region of residence, and socioeconomicstatus (measured as the neighborhoodincome quintile). Subjects withmissing data were excluded. Womenwere defined as having GDM using an algorithmanalogous to that used by the validatedregistry to exclude GDM: onehospitalization record or two ambulatoryphysician claims bearing the diagnosis ofdiabetes or GDM between 120 days beforeand 180 days after delivery.The primary outcome (CVD events)was defined as a hospitalization for acutemyocardial infarction, stroke, coronaryartery bypass, coronary angioplasty, orcarotid endarterectomy. The prespecifiedsecondary outcome (coronary artery disease[CAD] events) was hospitalizationfor acute myocardial infarction, coronaryartery bypass, or coronary angioplasty.Subsequent diagnosis with diabetes wasidentified if the woman entered the diabetesregistry postpartum. Although theregistry does not distinguish betweentypes, the majority of women developingdiabetes in this group would have type 2diabetes. All women were followed untilMarch 2007, with censoring on death.Subjects with GDM were matchedwith 10 subjects without GDM based onbaseline characteristics. Kaplan-Meiersurvival curves were constructed for bothoutcomes. Cox proportional hazards regressionwas used to model the associationof GDM with each outcome,accounting for the matched design of thestudy. For each outcome, an unadjustedmodel and a model adjusting for subsequentdiagnosis of diabetes as a timedependentcovariate were built. Theassumption of proportionality was verifiedby plotting log(–log[survival]) versuslog(time) to assess parallelism. The studywas approved by the institutional reviewboard of Sunnybrook Health SciencesCentre.
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