DIABETICMedicine

DOI: 10.1111/j.1464-5491.2010.02995.x

Original Article: Epidemiology

The risk of overt diabetes mellitus among women with
gestational diabetes: a population-based study

G. Chodick*†, U. Elchalal‡, T. Sella*†, A. D. Heymann*†, A. Porath*, E. Kokia*† and

V. Shalev*†
*Medical Division, Maccabi Healthcare Services, Tel Aviv, †Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv and ‡Department of Obstetrics & Gynecology,
Hadassah University Hospital and Hebrew University-Hadassah Medical School, Jerusalem, Israel

Accepted 16 February 2010

Abstract
Aims To determine the incidence of postpartum diabetes mellitus in the years following a diagnosis of gestational diabetes
mellitus (GDM) and to determine whether the severity of GDM, represented by the magnitude of the deviation of diagnostic tests
from the normal values or requirement for medications, is associated with the development of diabetes.
Methods A retrospective cohort study was performed among 185 416 pregnant women who had glucose challenge test or 3 h
oral glucose tolerance test (OGTT) in a large health maintenance organization in Israel. Subsequent diagnosis of diabetes was
ascertained by using an automated patient registry.
Results A total of 11 270 subjects were diagnosed with GDM, comprising 6.07% of the cohort. During a total follow-up
period of 1 049 334 person-years there were 1067 (16.9 per 1000 person-years) and 1125 (1.1 per 1000 person-years)
diagnoses of postpartum diabetes among GDM and non-GDM women, respectively. The cumulative risk of incident diabetes in
GDM patients with up to 10 years of follow-up was 15.7%, compared with 1% among the non-GDM population. Gestational
diabetes mellitus was associated with nearly an eightfold higher risk of postpartum diabetes after adjusting for important
confounders, such as socioeconomic status and body mass index. Among women with a history of GDM, the number of
abnormal OGTT values and use of insulin were associated with a substantially higher risk for developing diabetes.
Conclusions Three or four abnormal OGTT values and GDM requiring insulin or oral hypoglycaemic medications are
important predictors of postpartum diabetes risk in women with a history of GDM.
Diabet. Med. 27, 779–785 (2010)

Keywords diabetes mellitus, Gestational diabetes, glucose challenge test, Israel, oral glucose tolerance test
Abbreviations BMI, body mass index; CI, confidence interval; GCT, glucose challenge test; GDM, gestational diabetes
mellitus; HbA1c, glycated haemoglobin; ICD-9, The International Classification of Diseases (9th Revision); MHS,
Maccabi Healthcare Services; OGTT, oral glucose tolerance test

increased Cesarean section rate [4]. In addition, a history of

Introduction
GDM is associated with an increased long-term risk for the
Gestational diabetes mellitus (GDM) is defined as carbohydrate development of Type 2 diabetes mellitus [5].
intolerance of varying severity with onset or first recognition Following O’Sullivan’s classical report [6], many studies
during pregnancy [1]. In the USA, GDM affects between 2% and have documented the association between GDM and increased
5% of pregnant women [2], which is increasing with time in all risk of diabetes mellitus. However, a comprehensive systematic
ethnic groups [3]. Gestational diabetes mellitus is associated with review [7] of the studies on women with GDM found a large
adverse pregnancy outcomes, such as macrosomia and an variability in the cumulative incidence of diabetes mellitus,
ranging from 2.6 to over 70% in studies with a follow-up of
6 wk to 28 years postpartum. In addition, most of these
Correspondence to: Gabriel Chodick, PhD, Maccabi Healthcare Services, 27
Ha’Mered Street, Tel Aviv 68125, Israel. studies were limited by selective and small patient numbers
E-mail: [email protected] (n < 1000), short length of follow-up (<2 years), use of diverse

ª 2010 The Authors.

Journal compilation ª 2010 Diabetes UK. Diabetic Medicine, 27, 779–785 779
DIABETICMedicine Risk of overt diabetes following gestational diabetes • G. Chodick et al.

tests for glucose tolerance in pregnancy, and lack of [11] modification of the National Diabetes Data Group criteria
information on potential risk factors, such as personal conversion method, based on the presence of two or more of the
anthropometric measures or severity of GDM. following values in the 100 g OGTT: fasting serum glucose
In Israel, the standardized modality of screening is a glucose concentration exceeding 5.3 mmol ⁄ l (95 mg ⁄ dl); 1 h serum
challenge test (GCT), a measurement of serum glucose glucose concentration 10.0 mmol ⁄ l (180 mg ⁄ dl) or above;
concentration 1 h after a 50 g oral glucose load. A glucose 2 h serum glucose concentration exceeding 8.6 mmol ⁄ l
value of 7.8 mmol ⁄ l (140 mg ⁄ dl) or above is considered (155 mg ⁄ dl); and 3 h serum glucose concentration exceeding
abnormal and necessitates a second test, the 3 h oral glucose 7.8 mmol ⁄ l (140 mg ⁄ dl). All other study subjects were defined as
tolerance test (OGTT), for diagnosis of GDM. non-GDM.
In the Diabetes Prevention Program, both lifestyle
modification (such as body weight loss) and treatment with
Data collection and outcomes
metformin were found to be effective in delaying the progression
from impaired glucose tolerance to diabetes mellitus in women We examined the MHS database records of women in the study
with previous GDM [8]. Thus, calculating the exact long-term cohort from date of glucose challenge testing in the most recent
patterns of diabetes mellitus incidence in women with GDM and pregnancy to death, leaving MHS, date of diagnosis of
identifying patients at increased risk is of growing importance for postpartum diabetes mellitus, or 1 June 2009, whichever
effective screening and evidence-based case management. Given occurred earlier. Diagnosis of postpartum diabetes was
the considerable variability in the reported risk of diabetes detected using the patient’s entry data to the MHS Diabetes
mellitus among GDM patients, we sought to determine the long- Registry during this period. The MHS database was used to
term incidence of postpartum diabetes mellitus in the years collect a range of clinical and demographic parameters at index
following a diagnosis of GDM and to examine whether severity date. Height and weight were measured by a nurse or a physician
of GDM is associated with a higher risk of developing diabetes during office visits. Body mass index (BMI) was categorized into
mellitus. normal weight (<25 kg ⁄ m2), overweight (25–29 kg ⁄ m2) and
obese (‡30 kg ⁄ m2) using the World Health Organization
classification [12]. Socioeconomic level was categorized into
Patients and methods
quintiles according to the poverty index of the member’s
Maccabi Healthcare Services (MHS) is the second largest health enumeration area as defined by 1995 national census based on
maintenance organization in Israel, insuring 1.8 million several parameters, including household income, educational
members countrywide. In 2008, MHS covered 24.6% of the qualifications, crowding, material conditions and car ownership
total population and 26.1% of the 1.56 million Israeli women [13]. Gestational diabetes mellitus was further categorized into
aged 15–45 years. The annual number of births in MHS GDM with no insulin treatment, managed conservatively, and
(n = 39 291) comprised 24.1% of all births in Israel [9]. GDM requiring treatment with insulin or oral hypoglycaemic
According to the Israeli National Health Insurance Act, MHS agent, which was identified through pharmaceutical purchases.
may not bar any citizen who wishes to join it, and therefore every Data on mortality were retrieved from the Israel National
section in the Israeli population is represented in MHS. Population Registry, which maintains a registry of all citizens and
Nonetheless, MHS coverage in the non-Jewish populations is permanent residents, using record linkage based on a unique
substantially lower compared with the Jewish one. identification number. To control for differences in access to care
Over recent years, MHS has developed a central registry and an increased frequency of laboratory tests for detection of
consisting of all patients diagnosed with diabetes mellitus using diabetes mellitus among GDM patients, we included the number
the following entry criteria: laboratory test results of glycated of postpartum 75 g OGTT and fasting plasma glucose tests in the
haemoglobin (HbA1c) ‡ 7.25% or glucose ‡11.1 mmol ⁄ l multivariable models.
(200 mg ⁄ dl), (for individuals that are included in the register
on this criterion alone, supporting data for the diagnosis of
Statistical analysis
diabetes is required at 6 months), or two or more purchases of
diabetes medication over a 2 month period. Also included are The Chi-square test for categorical variables and analysis of
patients with a diagnosis of diabetes (according to ICD-9 code) in variance for continuous variables were performed to determine
the medical chart with HbA1c ‡ 6.5% or fasting glucose significant differences in baseline characteristics between study
‡6.9 mmol ⁄ l (125 mg ⁄ dl). These criteria have been validated groups. We used the Kaplan–Meier method to calculate the
and provide a specificity of 99.9% [10]. cumulative incidence rate for the development of postpartum
We collected data on all 50 g glucose challenge tests performed diabetes. The proportional Cox regression model with years
in MHS between 13 March 1995 and 27 May 2009. We of follow-up as the time scale was used to estimate hazard
excluded all women who had any indication of pre-existing ratios and 95% confidence intervals (CI) [14] for variables
diabetes mellitus, who had received infertility treatments or who significantly associated with increased risk of developing
were not in the relevant age range (15–50 years old). Women postpartum diabetes. Significance level was set at P = 0.05.
with GDM were defined according to the Carpenter & Coustan The proportional hazards assumption was checked graphically

ª 2010 The Authors.

780 Journal compilation ª 2010 Diabetes UK. Diabetic Medicine, 27, 779–785
 Original article DIABETICMedicine

and found to be reasonably fulfilled. Survival analyses were compared with 1% among the non-GDM population. The risk
repeated with restriction only for patients with GDM. of developing diabetes mellitus among GDM subjects increased
linearly with follow-up time, with no evidence of a plateau in
incidence of 10 years postpartum. The similar cumulative
Results
incidence of diabetes mellitus over 9 years of follow-up in the
A total of 11 270 subjects were diagnosed with GDM, present cohort and a previous cohort from Melbourne
comprising 6.1% of 185 416 study subjects. Baseline (Australia), where the diagnosis of diabetes mellitus was based
characteristics of GDM and non-GDM patients are given in on a 75 g OGTT and fasting blood glucose tests, are depicted in
Table 1. The GDM patients were significantly (P < 0.001) more Fig. 1.
likely to be older (32.7 vs. 30.6 years), overweight or obese In a multivariable logistic regression, women diagnosed with
(36.77 vs. 17.06%). Overall, 125 subjects died and 17745 GDM had an adjusted 7.7-fold higher hazard ratio (95% CI,
individuals left MHS during the total follow-up period. 7.1–8.4) of diabetes mellitus compared with non-GDM women.
During a total follow-up period of 1 049 334 person-years Other variables associated with diabetes mellitus were older age,
(5.7 person-years per participant), there were 1067 (16.9 per low socioeconomic status and BMI. Women with a BMI of
1000 person-years) and 1125 (1.09 per 1000 person-years) ‡30 kg ⁄ m2 had a hazard ratio of 5.1 (95% CI, 4.4–6.0) to
diagnoses of postpartum diabetes among GDM and non-GDM develop diabetes mellitus compared with normal-weight women
women, respectively. The cumulative risk of incident diabetes in (Table 2). In addition, having frequent fasting blood glucose tests
GDM patients with up to 10 years of follow-up was 15.7%, was also associated with increased risk of diabetes mellitus.

Table 1 Characteristics of study participants and clinical outcomes during follow-up period, according to gestational diabetes mellitus (GDM) status

No GDM (n = 174 146) GDM (n = 11 270) Total (n = 185 416)

n % of total n % of total n % of total P value*

Mean age at index 30.59 (5.18) 32.74 (5.51) 30.72 (5.22) <0.001
date [years (sd)]
Mean GCT 108.14 (28.55) 162.07 (27.01) 110.11 (30.24) <0.001
[mg ⁄ dl (sd)]
Mean GCT 6.01 (1.59) 9.00 (1.50) 6.12 (1.68)
[mmol ⁄ l (sd)]
Socioeconomic Lowest quartile 33067 18.99% 2190 19.43% 35257 19.02% <0.001
status Second quartile 67 515 38.77% 3991 35.41% 71 505 38.56%
Third quartile 29 447 16.91% 2076 18.42% 31 523 17.00%
Highest quartile 38 729 22.24% 2633 23.36% 41 362 22.31%
NA 5388 3.10% 380 3.37% 5768 3.11%
Smoking Current 17 996 10.33% 1207 10.71% 19 203 10.36% <0.001
Past 3338 1.92% 251 2.23% 3589 1.94%
Never 140 929 80.93% 9270 82.25% 150 199 81.01%
Unknown 11 883 6.82% 542 4.81% 12 425 6.70%
Body mass index <25 kg ⁄ m2 35 330 20.29% 1649 14.63% 36 979 19.94% <0.001
25–30 kg ⁄ m2 17 429 10.01% 1885 16.73% 19 314 10.42%
>30 kg ⁄ m2 12 285 7.05% 2259 20.04% 14 544 7.84%
Unknown 109 102 62.65% 5477 48.60% 114 579 61.80%
Parity 1 46 511 26.71% 2965 26.31% 49 476 26.68% <0.001
2 55 226 31.71% 3056 27.12% 58 282 31.43%
3 41 592 23.88% 2730 24.22% 44 322 23.90%
4+ 30 817 17.70% 2519 22.35% 33 336 17.98%
Year of 1995–1998 29 783 17.10% 1995 17.70% 31 778 17.14% <0.001
index date 1999–2002 40 477 23.24% 3439 30.51% 43 916 23.69%
2003–2005 37 616 21.60% 2788 24.74% 40 404 21.79%
2006–2009 66 270 38.05% 3048 27.06% 69 318 37.39%
Study end-points Mean 5.17 years (3.95 years) 5.70 years (3.65 years) 5.66 years (4.00 years) <0.001
follow-up
(sd)
Deaths 100 0.06% 25 0.22% 125 0.07% <0.001
Left MHS 17 114 9.83% 631 5.60% 17 745 9.57% <0.001
Incident DM 1067 0.61% 1125 9.98% 2192 1.18% <0.001

DM, diabetes mellitus; GCT, glucose challenge test; and MHS, Maccabi Healthcare Services.
*For comparisons between GDM and non-GDM populations.

ª 2010 The Authors.

Journal compilation ª 2010 Diabetes UK. Diabetic Medicine, 27, 779–785 781
DIABETICMedicine Risk of overt diabetes following gestational diabetes • G. Chodick et al.

Proportion with diabetes mellitus

0.2 crude incidence density rates of diabetes mellitus among GDM
MHS, GDM
subjects with two, three and four positive OGTT values were
9.7, 25.4 and 80.1 per 1000 person-years, respectively. The rate
Melbourne, GDM of development of diabetes among women who had GDM,
0.1
according to the number of positive OGTT values (log-rank
P < 0.001) is given in Fig. 2. According to this survival analysis,
the 10 year risk of diabetes mellitus in women with two
Melbourne, non-GDM abnormal values was 10.1%, compared with 22.1% and
51.5% in women with three or four abnormal values,
0.0 MHS, non-GDM
0 3 6 9 respectively. In a multivariable model, increased number of
Years abnormal OGTT values was associated with increased risk of
diabetes mellitus. Other factors positively associated with
FIGURE 1 The cumulative incidence of diabetes mellitus by life-table
postpartum diabeties mellitus among GDM patients were age
analysis in Maccabi Healthcare Services (MHS, Israel) and Melbourne
(Australia) [15]. at pregnancy, low gravidity, low socioeconomic status, obesity
and GDM treated with insulin (Table 3).

In stratified analyses among GDM patients, the number of

Discussion
positive values on 3 h OGTT was positively associated with
age, BMI, glucose challenge test level and an increased The results of the present study suggest that GDM, and
proportion of GDM patients treated with insulin. For particularly GDM treated with insulin or other hypoglycaemic
example, women who had all four values above the cut-off agents, and three or four abnormal OGTT values, are important
levels had a mean prior glucose challenge test level of predictors of future development of diabetes mellitus. As shown
180 mg ⁄ dl (10 mmol ⁄ l) and 29% of them were treated with in Fig. 1, the cumulative risk for diabetes mellitus in the present
insulin, compared with 159 mg ⁄ dl (8.83 mmol ⁄ l) and 5.7% study is almost identical to the results of a previous study from
among women with GDM who had two positive values. The Mercy Hospital for Women in Melbourne, Australia [15], in

Table 2 Adjusted hazard ratios and 95% confidence intervals (CI) for factors associated with diabetes mellitus in women with and without a history
of gestational diabetes

n Hazard ratio 95% CI P value*

Age Per year 185 415 1.03 (1.02, 1.04) <0.001

Parity 1 49475 1 (ref.) — —
2 58 282 0.80 (0.70, 0.91) <0.001
3 44 322 0.77 (0.68, 0.87) <0.001
4+ 33 336 0.80 (0.71, 0.91) <0.001
Body mass <25 kg ⁄ m2 36 978 1 (ref.) — —
index (kg ⁄ m2) 25–30 kg ⁄ m2 19 314 2.28 (1.93, 2.71) <0.001
>30 kg ⁄ m2 14 544 5.12 (4.38, 5.97) <0.001
Missing 114 579 1.34 (1.14 1.58) <0.001
Socioeconomic Highest quartile 35 257 1 (ref.) — —
Status† Third quartile 71 505 1.22 (1.06, 1.41) 0.006
Second quartile 31 523 1.29 (1.14, 1.45) <0.001
Lowest quartile 41 362 1.66 (1.45, 1.90) <0.001
Number of None 29 394 1 (ref.) — —
postpartum 1 47 353 3.08 (1.89, 5.01) <0.001
glucose tests 2 33 280 2.93 (1.80, 4.78) <0.001
3–5 48 160 4.67 (2.97, 7.36) <0.001
6–10 21,600 10.01 (6.38, 15.71) <0.001
11 or more 5628 35.91 (22.88, 56.35) <0.001
Smoking† Never 19 203 1 (ref.) — —
Current 3589 1.10 (0.95, 1.26) 0.197
Past 150 198 0.85 (0.64, 1.14) 0.271
GDM No 174 145 1 (ref.) — —
Yes 11 270 7.70 (7.05, 8.41) <0.001

*P value for deviation from 1.

†Patients with missing data are not shown.

ª 2010 The Authors.

782 Journal compilation ª 2010 Diabetes UK. Diabetic Medicine, 27, 779–785
 Original article DIABETICMedicine

found in studies from Ontario [16] and Nova Scotia [17] in

No. of abnormal values Canada, based on administrative service claims. The results from
2
0.6 3 all four large cohort studies indicate that gestational diabetes is
4 associated with a long-term increased risk of diabetes, with no
Cumulative incidence

indication of leveling-off after 5 years of follow-up, as was

suggested in a previous systematic review of 28 studies that were
0.4
published between 1965 and 2001 [7]. In addition to differences
between investigated populations in risk factors such as parity,
prepregnancy BMI, pregnancy weight gain and more general
0.2 differences between investigated populations such as ethnicity
and lifestyle, this discrepancy may be attributed to many of the
reviewed studies being relatively small (n < 1000) or having only
0.0 a short follow-up period, and therefore statistically
0 2 4 6 8 10 12 14 underpowered to detect a significant long-term increase in risk.
Follow-up (years) In the multivariable risk factor analysis, women with a history
of GDM had a nearly eightfold higher risk of developing
FIGURE 2 The cumulative incidence of diabetes mellitus by life-table postpartum diabetes mellitus compared with non-GDM women.
analysis during a 14 year period of follow-up among gestational diabetes
Our risk estimate is well within the 95% confidence interval of a
patients, according to number of abnormal oral glucose tolerance test values.
pooled relative risk calculated in the Mercy Hospital study [15],
as well as in a meta-analysis of six controlled follow-up studies
which 17% of the women who were diagnosed with GDM [18]. However, a substantially higher adjusted hazard ratio
developed diabetes within 10 years postpartum, based on 75 g (37.28; 95% CI, 34.00–40.88) was found in the Ontario cohort
and fasting blood glucose tests. Somewhat higher risks were study [16] on 659 164 subjects. This exceptionally high relative

Table 3 Adjusted hazard ratios and 95% confidence intervals (CI) for factors associated with diabetes mellitus in women with a history of gestational diabetes

n Hazard ratio 95% CI P value*

Age Per year 11270 1.04 (1.03, 1.05) <0.001

Parity 1 2965 1 (ref.) — —
2 3056 0.86 (0.72, 1.02) 0.08
3 2730 0.80 (0.67, 0.95) 0.009
4+ 2519 0.81 (0.68, 0.95) 0.01
Socioeconomic Highest quartile 2190 1 (ref.)
status† Third quartile 3991 1.08 (0.89, 1.32) 0.424
Second quartile 2076 1.14 (0.97, 1.35) 0.111
Lowest quartile 2633 1.40 (1.16, 1.68) <0.001
Body mass index <25 kg ⁄ m2 1649 1 (ref.) — —
25–30 kg ⁄ m2 1885 1.68 (1.33, 2.12) <0.001
>30 kg ⁄ m2 2259 2.68 (2.16, 3.33) <0.001
Missing 5477 1.13 (0.90, 1.42) 0.298
Smoking† Never 1207 1 (ref.) — —
Current 251 1.09 (0.90, 1.32) 0.378
Past 9270 0.83 (0.54, 1.29) 0.408
Abnormal OGTT 2 7849 1 (ref.) — —
values 3 2753 1.92 (1.67, 2.20) <0.001
4 668 4.00 (3.40, 4.71) <0.001
GDM treatment Conservative 10 256 1 (ref.) — —
Insulin ⁄ oral hypoglycaemic 1014 2.77 (2.39, 3.20) <0.001
Number of postpartum glucose tests None 1234 1 (ref.) — <0.001
1 1639 1.96 (1.04, 3.70) 0.04
2 1567 1.73 (0.91, 3.26) 0.09
3–5 3252 2.27 (1.28, 4.05) 0.005
6–10 2330 4.44 (2.52, 7.84) <0.001
11+ 1248 12.51 (7.11, 22.01) <0.001

GDM, gestational diabetes mellitus; and OGTT, oral glucose tolerance test.
*P value for deviation from 1.
†Patients with missing data are not shown.

ª 2010 The Authors.

Journal compilation ª 2010 Diabetes UK. Diabetic Medicine, 27, 779–785 783
DIABETICMedicine Risk of overt diabetes following gestational diabetes • G. Chodick et al.

risk is intriguing given that the crude relative risk after 9 years of Some important limitations of our study include our inability
follow-up was less than 10. to control for important modifiable and non-modifiable risk
Among the GDM population, we found that three and four factors, such as physical activity [26] and family history of
abnormal OGTT values were associated with a nearly two- and diabetes [27]. Body mass index was missing for 48.6% and
fourfold higher risk of developing diabetes compared with 62.7% of the GDM and non-GDM women, respectively. The
women having two abnormal values, respectively. Although such small but statistically significant increased risk of diabetes
association has been rarely reported [19], our observation is mellitus in women with missing information on weight or
consistent with several studies indicating that among women height suggests that data on BMI was somewhat less available for
with an OGTT test, those with one abnormal value have a women with higher BMI. This potential information bias could
twofold greater risk of subsequent diabetes compared with have resulted in an overestimation of the association between
women having no abnormal values [20]. This pattern of linear GDM and diabetes mellitus. Also, similar to other diabetes
increase in the risk of diabetes mellitus with increasing number of registries, the MHS diabetes registry does not distinguish
abnormal OGTT tests reflects the continuum between normal between Type 1 and Type 2 diabetes mellitus; however, the
glucose tolerance, impaired glucose tolerance and ultimately, majority of women in whom diabetes develops after gestational
diabetes. diabetes tend to have Type 2 diabetes [15]. In one report [28], the
Body mass index was a strong predictor for the development of prevalence of glutamic acid decarboxylase antibodies (a marker
postpartum diabetes mellitus. Women with a BMI of 30 kg ⁄ m2 for autoimmune or Type 1 diabetes) in women with GDM
or above had more than a fivefold higher risk compared with suggested that only 5% of the women who developed diabetes
women at a normal BMI level. This is in agreement with many had Type 1 diabetes. The diagnosis of GDM remains
[21], but not all [22], studies on GDM patients that found a controversial, without universal acceptance of a particular set
positive association between pregestational, gestational and of diagnostic criteria; however, the crude rate of GDM in our
postgestational BMI and the risk of developing diabetes mellitus. study (6.1%) is comparable with a previous study among Jewish
This relationship has been explained by modifiable risk factors, women in Israel (5.7%) [29], supporting the external validity of
such as low level of physical activity, increased dietary fat, and our findings. Our definition of GDM was based on OGTT tests,
avoidance of other lifestyle factors that adversely influence and therefore women who had a glucose challenge test level of
insulin resistance [23]. Following several studies which have ‡7.8 mmol ⁄ l (140 mg ⁄ dl) but who did not have an OGTT (12%
shown that progression to Type 2 diabetes is potentially of the cohort) were considered as non-GDM women. This
preventable by lifestyle or medical intervention in high-risk conservative approach may have led to attenuated calculated risk
subjects [8], our results underline the importance of promoting ratios.
secondary prevention efforts aimed to prevent or control the Our study used survival analysis to assess a large cohort of
progression of gestational diabetes to Type 2 diabetes women with and without GDM to determine long-term
mellitus. cumulative risk of diabetes mellitus and predictors for later
The present historical prospective study examining the development of diabetes mellitus. Primary care providers can
association between GDM and postpartum diabetes mellitus is use our results of antepartum indices (e.g. number of abnormal
one of the largest done to date with respect to follow-up period OGTT values, GDM treated with insulin, older age, obesity
and size of study population. The utilization of the validated etc.) as informative risk markers to identify those at highest risk
MHS diabetes registry, with its high validity and on-going, real- for Type 2 diabetes who would most benefit from targeted
time updating reduces the threat of misclassification bias in our interventions to prevent or delay the progression of impaired
assessment of diabetes incidence. An additional strength of the glucose tolerance to Type 2 disease, such as frequent screening
present database study is the very low turnover rate of the study tests, lifestyle changes and use of anti-diabetic medications
population (approximately 10% discontinued membership [30].
during the entire study period), affording minimal loss to
follow-up, compared with relatively high losses to follow-up in
many of the previous longitudinal studies that have attempted to Competing interests
follow women with gestational diabetes [15,24,25]. The bias There was no external funding or support for the study. Gabriel
resulting from higher drop-out rates and diminished cohort Chodick had full access to all the data in the study and takes
retention is particularly important longer after delivery, and thus responsibility for the integrity of the data and the accuracy of the
is particularly important in long follow-up studies. Furthermore, data analysis.
nearly 85% of our cohort were tested for fasting blood glucose
during the follow-up period, thus reducing the bias resulting from
closer diabetes screening of GDM women. Other study References
advantages include a prospective study design, the use of
1 Metzger B, Coustan D. Summary and recommendations of the
administrative databases to avoid the problem of differential Fourth International Workshop-Conference on Gestational
recall bias, and the systematic and comprehensive collection of Diabetes Mellitus. Diabetes Care 1998; 21 (suppl 2): B161–
personal sociodemographic data and medical history. B167.

ª 2010 The Authors.

784 Journal compilation ª 2010 Diabetes UK. Diabetic Medicine, 27, 779–785
 Original article DIABETICMedicine

2 Ferrara A, Hedderson M, Quesenberry C, Selby J. Prevalence of 19 Bian X, Gao P, Xiong X, Xu H, Qian M, Liu S. Risk factors for
gestational diabetes mellitus detected by the National Diabetes Data development of diabetes mellitus in women with a history of ges-
Group or the Carpenter and Coustan plasma glucose thresholds. tational diabetes mellitus. Chin Med J 2000; 113: 759–762.
Diabetes Care 2002; 25: 1625–1630. 20 Carr D, Newton K, Utzchneider K, Tong J, Gerchman F, Kahn S
3 Ferrara A. Increasing prevalence of gestational diabetes mellitus: a et al. Modestly elevated glucose levels during pregnancy are asso-
public health perspective. Diabetes Care 2007; 30: S141–S146. ciated with a higher risk of future diabetes among women without
4 Hoffert Gilmartin A, Ural S, Repke J. Gestational diabetes mellitus. gestational diabetes mellitus. Diabetes Care 2008; 31: 1037–1039.
Rev Obstet Gynecol 2008; 1: 129–134. 21 Baptiste-Roberts K, Barone B, Gary T, Golden S, Wilson L, Bass E
5 Metzger B. Long-term outcomes in mothers diagnosed with gesta- et al. Risk factors for type 2 diabetes among women with gesta-
tional diabetes mellitus and their offspring. Clin Obstet Gynecol tional diabetes: a systematic review. Am J Med 2009; 122:
2007; 50: 972–979. 207–214.
6 O’Sullivan J, Mahan C. Criteria for the oral glucose tolerance test in 22 Cho N, Lim S, Jang H, Park H, Metzger B. Elevated homocysteine
pregnancy. Diabetes 1964; 13: 278–285. as a risk factor for the development of diabetes in women with a
7 Kim C, Newton K, Knopp R. Gestational diabetes and the incidence previous history of gestational diabetes mellitus: a 4 year prospec-
of type 2 diabetes: a systematic review. Diabetes Care 2002; 25: tive study. Diabetes Care 2005; 28: 2750–2755.
1862–1868. 23 Dornhorst A, Rossi M. Risk and prevention of type 2 diabetes in
8 Diabetes Prevention Research Group. Reduction in the incidence of women with gestational diabetes. Diabetes Care 1998; 21 (suppl 2):
type 2 diabetes with lifestyle intervention or metformin. N Engl J B43–B49.
Med 2002; 346: 393–403. 24 Löbner K, Knopff A, Baumgarten A, Mollenhauer U, Marienfeld S,
9 Bendelac J. Membership in Sick Funds 2008. Jerusalem: Israel Garrido-Franco M et al. Predictors of postpartum diabetes in
National Insurance Institute, 2009. women with gestational diabetes mellitus. Diabetes 2006; 55:
10 Heymann A, Chodick G, Halkin H, Kokia E, Shalev V. [Description 792–797.
of a diabetes disease register extracted from a central database]. 25 Golden S, Bennett W, Baptist-Roberts K, Wilson L, Barone B, Gary
Harefuah 2007; 146: 15–79. T et al. Antepartum glucose tolerance test results as predictors of
11 Carpenter M, Coustan D. Criteria for screening tests for gestational type 2 diabetes mellitus in women with a history of gestational
diabetes. Am J Obstet Gynecol 1982; 144: 768–773. diabetes mellitus: a systematic review. Gend Med 2009; 6 (suppl 1):
12 World Health Organization. Obesity: Preventing and Managing the 109–122.
Global Epidemic. Report of a WHO Consultation on Obesity, 3–5 26 Knowler W, Barrett-Connor E, Fowler S, Hamman R, Lachin J,
June 1997. Geneva, Switzerland: World Health Organization, Walker E et al. Reduction in the incidence of type 2 diabetes with
1998. lifestyle intervention or metformin. N Engl J Med 2002; 346:
13 Central Bureau of Statistics. Census of Population and Housing. 393–403.
State of Israel: Jerusalem, 1998. 27 Lauenborg J, Hansen T, Jensen D, Vestergaard H, Molsted-Peder-
14 Cox DR. Regression models and life tables (with discussion). J R sen L, Hornnes P et al. Increasing incidence of diabetes after ges-
Stat Soc Series B Stat Methodol 1972; 32: 187–220. tational diabetes: a long-term follow-up in a Danish population.
15 Lee A, Hiscock R, Wein P, Walker S, Permezel M. Gestational Diabetes Care 2004; 27: 1194–1199.
diabetes mellitus: clinical predictors and long-term risk of devel- 28 Beischer N, Wein P, Sheedy M, Mackay I, Rowley M, Zimme P.
oping type 2 diabetes: a retrospective cohort study using survival Prevalence of antibodies to glutamic acid decarboxylase in women
analysis. Diabetes Care 2007; 30: 878–883. who have had gestational diabetes. Am J Obstet Gynecol 1995;
16 Feig D, Zinman B, Wang X, Hux J. Risk of development of diabetes 173: 1563–1599.
mellitus after diagnosis of gestational diabetes. CMAJ 2008; 179: 29 King H. Epidemiology of glucose intolerance and gestational
229–234. diabetes in women of childbearing age. Diabetes Care 1998; 21
17 Russell C, Dodds L, Armson B, Kephart G, Joseph K. Diabetes (suppl 2): B9–B13.
mellitus following gestational diabetes: role of subsequent preg- 30 Metzger B, Buchanan T, Coustan D, De Leiva A, Dunger D,
nancy. BJOG 2007; 115: 253–260. Hadden D et al. Summary and Recommendations of the Fifth
18 Cheung N, Byth K. Population health significance of gestational International Workshop-Conference on Gestational Diabetes
diabetes. Diabetes Care 2003; 26: 2005–2009. Mellitus. Diabetes Care 2007; 30 (suppl 2): S251–S260.

ª 2010 The Authors.

Journal compilation ª 2010 Diabetes UK. Diabetic Medicine, 27, 779–785 785