International Journal of Gynecology and Obstetrics (2008) 101, 7476

a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m

w w w. e l s e v i e r. c o m / l o c a t e / i j g o

CLINICAL ARTICLE

Risk factors for pre-eclampsia in pregnant Chinese

women with abnormal glucose metabolism
Yu Sun, Huixia Yang , Wei Jie Sun
Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China
Received 3 September 2007; received in revised form 10 October 2007; accepted 14 October 2007

KEYWORDS
Abnormal glucose
metabolism;
Pre-eclampsia;
Risk factors;
Diabetes;
Body mass index

Abstract
Objectives: To investigate the incidence and risk factors for pre-eclampsia in pregnant Chinese
women with abnormal glucose metabolism. Methods: A retrospective cohort study was
performed on 1499 pregnant women with abnormal glucose metabolism at Peking University
First Hospital from January 1995 to December 2004. Results: The overall prevalence of preeclampsia in women with abnormal glucose metabolism was 9.4% (141/1499). The prevalence of
pre-eclampsia in women diagnosed with diabetes mellitus prior to pregnancy was higher than
that of gestational diabetes mellitus and gestational impaired glucose tolerance patients (29.1%
vs 8.7% and 7.8%, P b 0.01). Pre-pregnancy body mass index was significantly higher in women
with pre-eclampsia than in those without. A higher rate of pre-eclampsia was found in women
with chronic hypertension and those with poor glucose control. The independent risk factors
for pre-eclampsia were chronic hypertension and elevated pre-pregnancy body mass index.
Conclusions: The type of diabetes, chronic hypertension, and elevated pre-pregnancy body mass
index are high risk factors for pre-eclampsia in pregnant women with abnormal glucose
metabolism.
2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd.
All rights reserved.

1. Introduction
In the last decade, the 50-g oral glucose challenge test (GCT)
has been popularized, and management of gestational
impaired glucose metabolism has become standard in most

Corresponding author. Department of Obstetrics and Gynecology,

Peking University First Hospital, No.1 Xianmen Street, Beijing,
100034, China. Tel./fax: +86 10 66186087.
E-mail address: yanghuixia_99@yahoo.com (H. Yang).

hospitals in China. The incidence of maternal and fetal

complications such as infection, polyhydramnios, and neonatal respiratory distress syndrome has decreased remarkably. Pre-eclampsia, however, is still a common complication
among women with abnormal glucose metabolism during
pregnancy. Previous studies have shown that maternal and
fetal outcomes are seriously affected when abnormal glucose
metabolism is complicated with pre-eclampsia [1,2].
The incidence of pre-eclampsia in all pregnant women
was 6.57% in Peking University First Hospital, Beijing, China,
between January 1995 and December 2004. The incidence of

0020-7292/$ - see front matter 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd.
All rights reserved.
doi:10.1016/j.ijgo.2007.10.008

Risk factors for pre-eclampsia in pregnant Chinese women with abnormal glucose metabolism

75

Table 1 Blood glucose values at glucose challenge test (GCT) and oral glucose tolerance test (OGTT) and glycated hemoglobin
(HbA1C) levels among women in pre-eclamptic and non pre-eclamptic groups

PE
NPE

GCT (mmol/L)

OGTT (mmol/L)

HbA1C

No.

No.

BG

No.

FBG

1h

2h

3h

No.

Level (%)

141
1358

113
1259

10.0 3.6
9.6 2.2a

121
1239

6.1 2.1
5.5 1.4a

11.3 1.8
11.1 1.6

9.3 2.2
9.0 1.8

6.4 2.5
6.1 1.9

71
672

5.8 1.1
5.4 0.8 a

Abbreviations: GCT, glucose challenge test; OGTT, oral glucose tolerance test; BG, blood glucose; FBG, fasting blood glucose; HbA1C,
glycated hemoglobin; PE, pre-clamptic; NPE, non pre-eclamptic.
a
P b 0.01.

gestational hypertension and chronic hypertension was 3.05%

and 0.86%, respectively. The rate of pre-existing diabetes
mellitus was 0.42%. The prevalence of gestational diabetes
mellitus (GDM) and gestational impaired glucose tolerance
(GIGT) was 3.81% and 3.07%, respectively.
This retrospective study was designed to investigate
the risk factors for pre-eclampsia in pregnant women with
abnormal glucose metabolism to improve pregnancy
outcomes.

2. Methods
Of the 20,512 women who delivered at Peking University First
Hospital between January 1995 and December 2004, data
for 1499 pregnant women with abnormal glucose metabolism
were reviewed. A total of 141 cases were complicated with preeclampsia, while the remaining 1358 cases were not preeclamptic. The 1499 patients included 86 cases of diabetes
mellitus prior to pregnancy, 779 cases of GDM, and 634 cases of
GIGT. Of these 1499 patients, 1372 were screened using GCT and
1360 were diagnosed using a 75-g 3-hour oral glucose tolerance
test (OGTT). Glycated hemoglobin (HbA1C) results were only
available in 743 patients. The study was approved by the
Research Ethics Committee of the Peking University First
Hospital.
Diabetes mellitus was diagnosed prior to the start of pregnancy.
A diagnosis of GDM was based on a fasting blood glucose (FBG)
level N 5.8 mmol/L (105 mg/dL) on more than 2 occasions, or 2 or
more abnormal values of OGTT, with cut-off values of 5.8 mmol/L
(105 mg/dL), 10.6 mmol/L (190 mg/dL), 9.2 mmol/L (165 mg/dL),
and 8.1 mmol/L (145 mg/dL) at fasting, 1, 2, and 3 h, respectively.
GIGTwas diagnosed when there was only 1 abnormal value during
OGTT.
All patients were divided into 2 groups according to the
glycemic level after treatment: the well-controlled group and
the poorly-controlled group. Well-controlled was defined as
having FBG 5.8 mmol/L (105 mg/dL) and 2-hour postprandial
glucose level 6.7 mmol/L (120 mg/dL). All other patients were
considered poorly-controlled.
Pre-eclampsia was diagnosed as blood pressure 140/90 mm Hg
on 2 or more occasions of at least 6 hours apart and proteinuria
300 mg/24 h or 1 +dipstick after 20 weeks of gestation.
SPSS version 10.0 (SPSS, Chicago, IL, USA) was used for
statistical analysis. Categorical data were analyzed with 2 test
or Fisher exact test, and continuous data were compared using
the t test. Logistic regression was used for multiple factor
analysis.

3. Results
There was no statistical difference between women with and
without pre-eclampsia for maternal age (30.5 4.4 years vs
30.7 3.9 years, P N 0.05). Pre-pregnancy body mass index
(BMI, calculated as the weight in kilograms divided by height
in meters squared) and parity of those women in the preeclampsia group were significantly higher than women
without (27.6 4.7 vs 25.1 3.9, P b 0.01; 1.0 0.6 vs 0.8
0.6, P b 0.01).
The overall incidence of pre-eclampsia in the abnormal
glucose metabolism group was 9.4% (141/1499) and 29.1%
(25/86) in the diabetes mellitus group, which was much
higher than in the GDM and GIGT groups at 8.8% (68/779) and
7.8% (48/634), respectively (P b 0.01). In comparison, the
incidence of pre-eclampsia was 6.35% (1207/19,013) in the
non-diabetic group and 6.57% (1348/20,512) among all
pregnant women in the hospital during the study period.
In women with pre-eclampsia the GCT blood glucose
level, FBG level, and HbA1C level were all higher than in
women without pre-eclampsia (P b 0.01) (Table 1). Most of
the women with pre-existing diabetes mellitus were not
included in the GCT and OGTT group, but were included in
the HbA1c group.
The incidence of pre-eclampsia in the poorly-controlled
group was 14.0% (39/279) and 8.36% (102/1220) in the wellcontrolled group (x2 = 8.41, P b 0.01). Of all the patients,
1010 achieved euglycemia by diet alone. In these women the
incidence of pre-eclampsia was 9.9% (100/1010). Of the 489
women who received insulin, the incidence of pre-eclampsia
was 15.1% (74/489; P b 0.01).
A higher rate of pre-eclampsia was found among women
with chronic hypertension compared with those without
(33.3% vs 8.8%, P b 0.01). However, no difference was
found between women with or without poor obstetric
histories. Logistic regression was used for multiple factor

Table 2 Risk factors for pre-eclampsia in women with

gestational impaired glucose metabolism
Risk factor

OR

95% CI

Pre-pregnancy BMI
Chronic hypertension

1.131
7.174

0.006
0.030

1.036-1.234
1.207-42.63

Abbreviations: OR, odds ratio; CI, confidence interval; BMI, body

mass index.

76
analysis. Independent variables included age, parity, prepregnancy BMI, GCT results and OGTT, HbA1C level,
glycemic control, poor previous obstetric history, and
chronic hypertension. The dependent variable was preeclampsia. Elevated pre-pregnancy BMI and chronic
hypertension were found to be independent risk factors
(Table 2).

4. Discussion
Although the pathogenesis of pre-eclampsia and eclampsia
remains unclear, recent studies have demonstrated that the
incidence of pre-eclampsia is higher among women with
gestational impaired glucose metabolism. In the 1990s,
Garner et al. [3] found that the incidence of pre-eclampsia
in GDM patients was 24 times that of healthy pregnant
women. In 2002, Vambergue et al. [4] reported the incidences
of GDM with pre-eclampsia and GIGT with pre-eclampsia as
17.0% and 10.8%, respectively. stlund et al. [5] later
reported a study of 430,852 cases in which the incidence of
pre-eclampsia in 3448 women with GDM was much higher than
in women without GDM (6.1% vs 2.8%).
In the present study the pre-eclampsia rate of gestational
impaired glucose metabolism (including diabetes mellitus,
GDM, and GIGT) was 9.4% over the past decade, significantly
higher than in normal pregnancies. We also found that the
pre-eclampsia rate varied with different degrees of glucose
metabolism impairment. The pre-eclampsia rate of women
with diabetes was significantly higher than that of women
with GDM or GIGT. Therefore, it is necessary to carefully
monitor women with impaired glucose metabolism, particularly those with diabetes mellitus, for early diagnosis and
treatment of pre-eclampsia.
Our study has shown that GCTresult, FBG level, and HbA1C
level are closely related to the occurrence of pre-eclampsia
for women with abnormal glucose metabolism. This finding
indicates that the blood glucose level of women recently
diagnosed with gestational impaired glucose metabolism is an
important risk factor for pre-eclampsia. The main pathogenesis is that hyperglycemia can reduce prostacyclin and nitric
oxide production, enhancing vessel constriction and resulting
in abnormal blood flow and hypertension [6]. The finding that
the rate of pre-eclampsia was higher among insulin dependent pregnant women than in those using diet control alone
supports this theory. However, the incidence of pre-eclampsia
can be significantly reduced by well-controlled blood glucose
levels. In our study the incidence of pre-eclampsia in the wellcontrolled group was lower than in the poorly-controlled group
(8.36% vs 14.0%). Yogev et al. [7] reported that the severity of
GDM correlates with pre-eclampsia incidence, and better
control of glucose can reduce pre-eclampsia rate.
Several studies have investigated different theories for
risk factors for pre-eclampsia with gestational impaired
glucose metabolism. Barden et al. [8] believed that the
severity of insulin resistance and metabolic syndrome are
risk factors closely related to pre-eclampsia. Hinton and
Sibai [9] reported that the risk for pre-eclampsia increased

Y. Sun et al.
when diabetes was complicated with chronic hypertension,
renal disease, and mild proteinuria. In our study, using
logistic regression analysis, pre-pregnancy BMI and chronic
hypertension were shown as independent risk factors for preeclampsia with gestational impaired glucose metabolism.
Insulin resistance of obese patients is elevated, leading to
the increased response of small vessels to sympathetic nerve
activation. Meanwhile, hyperlipidemia leads to vessel
endothelial cell dysfunction. Hyperinsulinemia can also
cause hyperplasia of vessel smooth muscle cells, resulting
in narrow vessel cavity, higher blood resistance, and hypertension [10]. This might be the crucial pathogenesis of preeclampsia in women with gestational impaired glucose
metabolism. While chronic hypertension is accompanied by
glucose metabolism impairment, persistent hypertension
and hyperglycemia will exacerbate existing microvessel
changes. Capillary base membranes become thicker and
vessel cavities become narrower; subsequently, higher blood
pressure leads to pre-eclampsia. This pathogenesis is more
common among women with pre-gestational diabetes with
pregnancy. Therefore, it is critical to carefully monitor
pregnant women with both impaired glucose metabolism and
chronic hypertension. Well controlled blood glucose level
and stable controlled blood pressure can reduce the
incidence of pre-eclampsia.

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