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Risk
factors for development of diabetes mellitus in women with a history of
gestational diabetes mellitus
BIAN
Xuming 边旭明,
GAO Ping 高平,
XIONG Xiaoyan 熊晓燕,
XU Hang 许杭,
QIAN Meilun 钱美仑
and LIU Shanying 刘善英 Keywords:
gestational diabetes mellims . diabetes mellitus . oral glucose tolerance test Objective To
determine whether diabetes recurs in their later life when women have a history
of gestational diabetes mellitus (GDM) or abnormal glucose tolerance test
(impaired glucose tolerance, IGT). Methods
Three groups of women were investigated at 5-10 years postpartum. GDM
group (n = 45) had been diagnosed as having GDM in their previous pregnancy. IGT
group (n = 31 ) had a history of abnormal glucose tolerance test during previous
pregnancy. Normal control group (n = 39) was normal previous pregnant
population. Their previous obstetric and medical histories were thoroughly
reviewed. Fasting plasma glucose (FPG) and oral glucose (75 g) tolerance test (OGTT)
were repeated in all women. Results Diabetes
mellitus (DM) was diagnosed in 33.3% of patients in the GDM group, while in 9.7%
in the IGT group and in 2.6% in the normal control group. Incidence of recurring
DM in later life was significant higher in the GDM group (P = 0.017). When one
or more blood glucose values exceeding WHO criteria for diagnosis of diabetes in
their previous pregnancy, the incidence of DM in later life was 60% (3/5,
including GDM in women having four abnormal OGTT values), 41.7% (5/12) in women
having three, 25% (7/28) in women having two and 9.7% (3/31) in women having
one. The women with DM, also with a history of GDM and abnormal OGTT in previous
pregnancy, tends to have a high pregnant body mass index (BMI >25 kg/m2).
Conclusion The
women suffering from GDM during previous pregnancy have a high risk of
recurrence DM. Two or
more abnormal
OGTT values
during pregnancy, blood glucose level exceeding the maximal values at 1
and 2 hours after oral glucose loading and high pregnant BMI are concluded to be
useful factors in predicting the recurring DM in their later life.
Gestational diabetes mellitus (GDM) is defined as abnormal carbohydrate
metabolism of various severity first diagnosed during pregnancy, irrespective of
whether blood glucose levels is in the normal range after delivery.1 It
occurs in 1% - 8% of all pregnancies.2,3 GDM
is a high risk factor for
an adverse
pregnancy outcome,
which increases perinatal mortality and morbidity. Approximately 40% of
mothers with GDM will subsequently develop overt diabetes
mellitus (DM)
within 20
years after
the pregnancy. 4 This
is a retrospective study. Women with a history GDM were followed up at 5 - 11
years postpartum and the incidence of DM in this selective population was
assessed. Predictive factors of recurring DM were also investigated in order to
find possible ways of preventing or delaying the occurrence of DM in later life.
METHODS Original
case group
Since December 1984, all pregnancies presenting
for prenatal care at the Obstetric Out-patient Clinic of Peking Union Medical
College (PUMC) Hospital have been routinely screened for GDM. A 100 g oral
glucose tolerance test (OGTF) was performed at 24- 28 gestational weeks. The
diagnostic criteria recommended by the National Diabetes Data Group (NDDG) were
adopted.5 Blood glucose values
exceeding the following criteria were considered abnormal: fasting plasma
glucose (FPG) > 5.8 mol/L, at 1 hour > 10.6 mol/L, at 2 hours > 9.2
mmol/L, at 3 hours >8.1 mmol/L. Pregnancies
which had
two or
more abnormal OGTY blood glucose values were diagnosed as GDM. Women who
only had one abnormal value were considered
as having impaired glucose tolerance (IGT). From
December 1984
to December
1990, 49 pregnancies were
diagnosed as GDM, and 36 as IGT.
Eighty-five pregnancies
during the
same period
were recruited as normal control. OGGT of all normal controls were in the
normal range. They also matched well in age, social background and gestational
age of birth with GDM and IGT pregnancies. The mean age of all pregnancies was
29 years (range: 23 to 40). Gestational age at birth was 34 - 42 weeks. Follow-up
methods
From
1995 to 1996, each woman from original case group was contacted by letter, phone
calls and home visits inquiring about the possibility of returning to our
obstetric out-patient clinic
for follow-up.
Informed consent
was obtained and an approval was obtained from the Ethics Committee of
PUMC Hospital. For each returning woman, a questionnaire was completed and blood
glucose levels were tested. Other clinical parameters were measured, including
the patient's weight and height, for calculating body mass index (BMI). They
were also questioned about any existing symptoms of DM.
If DM had
been diagnosed,
the information about the process of diagnosis, where and when, would be
filed. Fasting plasma glucose (FPG) was tested in all subjects. 75 g OGTT was
ordered when anyone had a normal value of fasting plasma glucose. The subject
took 300 ml cooled solution containing 75 g of glucose by mouth, and then
capillary blood samples were taken at required intervals. Blood glucose levels
were measured using glucose oxidase method.
According to the criteria of the World Health Organization,6
the patients were considered as having DM, when FPG was ≥
7.8 mmol/L and, or at 2 hours was ≥
11.1 mmol/L. When FPG was < 7.8 mmol/L and at 2 hours was 7.8 - 11.1 mol/L,
patients were diagnosed as having IGT. Statistical
analysis A
computer
statistical package,
STATA (Version 3.0), was
adopted to perform all statistical analyses. The χ2
test and the Fisher exact test were used for comparison of frequencies. All
tests were two-tailed and a P value < 0.05 was considered significant. RESULTS Among
49 women with a history of GDM, 45 (GDM group, n= 45) returned to our clinic
with a response rate of 91.85%, while 31 (IGT group, n: 31) of 36 women with a
history of IGT returned with a rate of 86.1%. In the normal control group, 39 of
85 (control group, n: 39) visited our clinic with the rate of only 45.9 %. Incidence
of recurring DM
The overall incidence of recurring DM was 16.5 % (19/115) in the all
three groups. Among the 19 cases with recurring DM, 18 were diagnosed before
returning back to our clinic and 1 was during the follow-up study.
As shown in Table 1, the incidence of recurring DM
in the GDM group is twelve fold over that of the control group (P < 0.05).
There is no statistically significant difference between the IGT group and
control group. During the follow-up study, 6 women were diagnosed as IGT.
Characteristics
of abnormal OGTT values in previous GDM The
characteristics of abnormal
0GTT values
of gestational diabetes mellitus and the incidence of DM occurring at 5 -
10 years postpartum are shown in Table 2. Abnormal OGTT in their previous
pregnancy is positively correlated with the subsequent DM.
The women suffering from DM during 5 - 10 years postpartum, or IGT tended
to have more abnormal values of OGTT during their previous pregnancy. The
tendency is more apparent in the DM and IGT group than in the normal controls.
Among
the 18 patients who were diagnosed as having DM before lemming to our follow-up,
the abnormal glucose values of OGTT tested during previous pregnancy were often
found at 1 hour and 2 hour (Table 3).
Body
mass index (BMI) and the occurrence of diabetes mellitus The
relationship between BMI and DM is shown in Table 4.
In the GDM group, 8/45 (17.8%) was overweight. However, only 5.1% (2/39) in the
control group were overweight. The risk of recurring DM significantly increased
in the women who had higher antepmtum BMI ( ≥25
kg/m2).
DISCUSSION Significance
of OGTT during pregnancy When
we started the screening for GDM in pregnancies using 3 hours OGTT, we thought
that only women with either a family history of DM or a poor obstetrical history
should be taken into account. However, among the 45 pregnancies diagnosed as
having GDM in our study, only 1 had a family history of DM, 17 had positive
obstetrical history and 2 had both. That means,
if we screened the pregnancies only according to these two high risk
factors, over half of the cases of GDM would have been missed. So we realized
the importance of screening all patients at 24 - 28 weeks of gestation using
OGTT. Nevertheless,
performing an OGTT in pregnancy has certain problems. It is time-consuming and
75 to 100 g of glucose taken by mouth often causes nausea. The women often tend
to refuse four venepunctures within 3 hours. All these make the subjects
reluctant to participate in the screening. The study indicated that blood
glucose values at 1 hour and 2 hours after ingestion of oral glucose load were
the most reliable one in identifying diabetes mellitus. The simplified 50 g
glucose tolerance test, which only
need 1 hour blood glucose to be tested, is
a useful test for identifying the majority of the high risk gravida.7 When
the result of the simplified 50 g test is abnormal, 75 g OGTT should be ordered
to confirm the sensitivity and specificity of the diagnosis..8 GDM
as a high risk factor of recurring of DM In
our study, 33% of the patients with a history of GDM were diagnosed as having DM
during the follow-up, while only 2.6 % in the control group. This shows that GDM
is a high risk factor for the subsequent development of DM. Other studies with
long-period of follow-up have shown an even higher rate of subsequent
development of DM. Henry et al9
reported a rate of 40% at 17 years postpartum. O' Sullivan4
reported a rate of > 50% during a 28 years follow-up.
In China, long term
follow-up data is not available yet to fully assess the true rate. OGTT
in predicting DM
The results of our retrospective study show that there is a positive
correlation between abnormal OGTF in previous pregnancy and recurring DM. We
also found that abnormal plasma glucose values at 1 hour and 2 hours were the
most predictive regarding the development of DM. A possible explanation for this
is insulin resistance. 10
Following the ingestion of 100 g glucose, a normal pregnant woman
secretes additional mounts of insulin to accelerate the metabolism of the
glucose. The insulin reaches peak level at 30 - 60 minutes after orally
ingestion of glucose, and then
the blood
glucose level
decreased appropriately. However, for women with GDM, the capacity of
compensation in this situation is damaged because they do not have the ability
to raise insulin output, due to pancreaticβ
cell dysfunction. Blood sugar level declines at a slower rate than that of the
normal and then the 1 hour and 2 hours glucose level are elevated, compared with
normal pregnant women. If
pancreatic β
cells are not able to respond appropriately during pregnancy, the women are more
at the risk of suffering from GDM. 11 The
observation of abnormal values of OGTT in previous pregnancy was not found to be
a statistically significant independent variable because of the time limit of
our study. It can only show a trend for a positive correlation. Obesity
and DM
In 1982, O' Sullivan4 indicated
that there was a close relationship between obesity and DM after a 10 - 16 years
follow-up. We also found that the
women with abnormal OGTT and BMI over 25 kg/m2, had relatively high
risk of development of DM. The risk was about 3.5 fold over the women with low
BMI. Antepartum obesity was related to the subsequent development of DM. The
result is quite similar to other recently published studies. 12,13
Obesity may also play a causative or possibly additive role in the
development of DM after GDM. Continuous
excessive stimulation
on pancreatic
β
cells leads
to hyperinsulinemia, which may alter the sensitivity of the target cells
and lower their sensitivity to insulin. In
conclusion, we found that: 1. Women with a history of GDM are at high risk of
developing GM at 5 - 10 years postpartum; 2. Abnormal plasma glucose values at 1
hour and 2 hours of OGTT are important indicators in predicting the development
of DM; 3. High maternal BMI during pregnancy is an additive risk factor for
developing GM. REFERENCES
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Received August 15, 1999 )
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China (Bian XM, Gao P, Xiong XY, Xu H, Qian ML and Liu SY)
Chin Med J 2000; 113(8): 759-762 |
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