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Articles

Type 2 diabetes mellitus after gestational diabetes:


a systematic review and meta-analysis
Leanne Bellamy, Juan-Pablo Casas, Aroon D Hingorani, David Williams

Summary
Background Women with gestational diabetes are at increased risk of developing type 2 diabetes, but the risk and time Lancet 2009; 373: 1773–79
of onset have not been fully quantified. We therefore did a comprehensive systematic review and meta-analysis to See Editorial page 1735
assess the strength of association between these conditions and the effect of factors that might modify the risk. See Comment page 1738
Northwick Park Hospital,
Methods We identified cohort studies in which women who had developed type 2 diabetes after gestational diabetes London, UK (L Bellamy MBBS);
were followed up between Jan 1, 1960, and Jan 31, 2009, from Embase and Medline. 205 relevant reports were hand Department of Epidemiology
and Population Health,
searched. We selected 20 studies that included 675 455 women and 10 859 type 2 diabetic events. We calculated and London School of Hygiene and
pooled unadjusted relative risks (RRs) with 95% CIs for each study using a random-effects model. Subgroups analysed Tropical Medicine, London, UK
were the number of cases of type 2 diabetes, ethnic origin, duration of follow-up, maternal age, body-mass index, and (J-P Casas MD); Department of
diagnostic criteria. Epidemiology and Public
Health, University College
London, London, UK
Findings Women with gestational diabetes had an increased risk of developing type 2 diabetes compared with those (Prof A D Hingorani FRCP); and
who had a normoglycaemic pregnancy (RR 7·43, 95% CI 4·79–11·51). Although the largest study (659 164 women; Institute for Women’s Health,
University College London,
9502 cases of type 2 diabetes) had the largest RR (12·6, 95% CI 12·15–13·19), RRs were generally consistent among
London, UK (D Williams FRCP)
the subgroups assessed.
Correspondence to:
Dr David Williams, Institute for
Interpretation Increased awareness of the magnitude and timing of the risk of type 2 diabetes after gestational diabetes Women’s Health, University
among patients and clinicians could provide an opportunity to test and use dietary, lifestyle, and pharmacological College London, 250 Euston
interventions that might prevent or delay the onset of type 2 diabetes in affected women. Road, London NW1 2PG, UK
d.j.williams@ucl.ac.uk

Funding None.

Introduction elucidation of the causes of these disorders, and for the


Gestational diabetes mellitus is defined as glucose prediction and possible prevention or delay of the
intolerance that is first detected during pregnancy.1 In the development of type 2 diabetes in women. We therefore
USA, this condition affects 135 000 pregnancies (3–5% of did a comprehensive systematic review and meta-
all pregnancies) per year.2,3 Shortly after delivery, glucose analysis to quantify the overall risk of women with
homoeostasis is restored to non-pregnancy levels, but gestational diabetes mellitus developing type 2 diabetes
affected women remain at high risk of developing type 2 mellitus, and to assess the effect of factors that might
diabetes mellitus in the future.4,5 modify this risk.
For any population and ethnic group, the risk of
gestational diabetes indicates the underlying frequency of Methods
type 2 diabetes.2,6 The incidences of gestational diabetes Search strategy and selection criteria
and type 2 diabetes are rising throughout the world, with We did an electronic search of Embase from 1974 to
huge health-care and economic costs.6,7 Diabetes pre- Jan 31, 2009, and Medline from 1960 to Jan 31, 2009,
disposes individuals to cardiovascular, renal, and retinal without language restrictions. Search term combinations
diseases, costing US$91·8 billion per year in the USA.8 were “gestational diabetes”, “diabetic pregnancy”,
Women who have had gestational diabetes are advised “diabetes mellitus”, “type 2 diabetes mellitus”, “NIDDM”,
to have their glucose tolerance assessed 6 weeks after and “non-insulin dependent diabetes mellitus”. All
delivery.9 However, low rates of attendance at the 6-week reference lists from the main reports and relevant reviews
follow-up10,11 suggest that health-care professionals, were hand searched for additional eligible studies.
women with gestational diabetes, or both, do not realise We identified retrospective and prospective cohort
the importance of this disorder as an early warning sign studies, reported between Jan 1, 1960, and Jan 31, 2009, in
of the susceptibility to develop type 2 diabetes in the which pregnant women of any parity or ethnic origin were
future; therefore an opportunity to promote health and identified as having gestational diabetes (exposed group)
prevent disease is missed. Moreover, no consensus exists and normoglycaemic pregnancies (control group).
on how and whether mothers should continue to be The outcome studied was the development of type 2
monitored after this period. diabetes at least 6 weeks after the end of the index
The association between gestational diabetes and pregnancy, and was defined with an oral glucose tolerance
type 2 diabetes mellitus has implications for the test or fasting plasma glucose concentration, or both,

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Articles

measured to assess heterogeneity with RevMan and


435 potentially relevant titles and Phase 1 STATA (version 10.0). We investigated potential sources
summaries identified of identified heterogeneity among studies by stratification
according to the number of cases of type 2 diabetes
230 excluded: (<100, 100–500, and >500); ethnic origin (white,
No desirable outcomes non-white, and mixed race populations); average
Outcomes during pregnancy only
Editorials follow-up (<5 years and ≥5 years); average maternal age
Letters at index pregnancy (<30 years and ≥30 years); average
News articles
body-mass index of mothers at the end of their index
pregnancy and follow-up (<25 kg/m², 25–30 kg/m²,
205 (47%) full-text studies reviewed Phase 2 >30 kg/m²); study design (prospective and retrospec-
tive); and variation in criteria used in each study to
137 excluded (webappendix pp 1–9)
diagnose gestational diabetes and type 2 diabetes. In
30 reviews these analyses, we used 99% CIs to reduce the potential
2 case-control studies for chance differences arising from multiple testing.
4 cross-sectional studies
1 follow-up <6 weeks Small-study bias and publication bias were assessed with
18 outcome inferred only funnel-plot analysis. RRs were unadjusted because they
12 no association with study question
23 insulin resistance after gestational
were calculated from raw data.
diabetes
15 only gestational diabetes assessed Role of the funding source
10 only type 2 diabetes assessed
1 foreign, not available in There was no funding source for this study. The
British Library corresponding author, on behalf of all authors, had full
20 repeat study group
1 normoglycaemic group lost to access to all the data in the study and had final
follow-up responsibility for the decision to submit for publication.

68 (16%) relevant studies—ie,


Results
cohort studies in women with Phase 3 Figure 1 shows the study selection process (reasons for
gestational and type 2 diabetes mellitus exclusion are listed in webappendix pp 1–13). 48 of
68 full-text reports meeting all the inclusion criteria were
48 excluded (webappendix pp 10–13) subsequently excluded because of the absence of an
because no control group appropriate control or reference population. The
20 remaining studies (table),5,15–18,21–35 contributed 675 455
20 (5%) included in meta-analysis Phase 4
women with type 2 diabetes to the meta-analysis, and
31 867 of these had previous pregnancies affected by
Figure 1: Study selection process
gestational diabetes with a total of 10 859 incident cases
Modified with permission from Centre for Reviews and Dissemination.20 of type 2 diabetes.
Figure 2 shows the overall RR of women developing
according to the National Diabetes Data Group,12 WHO type 2 diabetes after a pregnancy complicated by
criteria,13 countrywide guidelines,14 or specified local gestational diabetes with evidence of heterogeneity in
criteria.15,16 Cohort studies of women with diabetes the risk estimate. Generally, small studies had large
mellitus before the index pregnancy were excluded. effect estimates (figure 3), but the largest study18 included
in the meta-analysis had the largest effect estimate
Data gathering and statistical analysis (figure 2).
Two independent reviewers (LB and DW) checked each Figure 4 shows the potential sources of heterogeneity
full-text report for eligibility, and extracted and tabulated by study characteristics, participant characteristics, and
all relevant data. Disagreement was settled by consensus diagnostic criteria for gestational diabetes and type 2
between all authors. If there was more than one report diabetes. Effect estimates were broadly consistent in all
relating to the same cohort, the report with the information the subgroups analysed (figure 4B; figure 4C). There was
See Online for webappendix most relevant to our analysis was included (webappendix some heterogeneity in effect estimates when studies
for studies excluded at full-text review). Additional tabular were grouped according to the number of cases of type 2
data, including the largest study in the meta-analysis, were diabetes (<100, 100–500, and >500; figure 4A).
provided by direct contact with the corresponding Heterogeneity was reduced by exclusion of the largest
authors.17,18 All procedures conformed to the guidelines for study (χ²=1·48, df=1, p=0·22, I²=32·2%). No significant
meta-analysis of observational studies in epidemiology.19 heterogeneity was evident from the subgroup analysis of
We used RevMan (version 5) to calculate unadjusted the criteria used for the diagnosis of gestational diabetes
summary relative risks (RRs) with 95% CIs, using a and type 2 diabetes in the studies included in the analysis
random-effects model for all analyses. τ² and I² were also (figure 4C).

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Study type, year, country Ethnic Mean maternal age GDM criteria Total women Mean follow-up Definition of T2DM
origin (years; SD or 95% CI) studied (degree of (SD or 95% CI)
of women with matching GDM/
GDM/non-GDM non–GDM)
Feig et al18 Retrospective cohort, 2008, Mixed 29·3 (5·5) Canadian Institute for 659 164 5·2 yearsi Ontario Diabetes
Canada Health Information Databaseii,37
(discharge summary)36
Lee H et al15 Prospective cohortiii, 2008, Non-white 33·6 (4·8) National Diabetes Data 1736v (248 IGT) 2·1 yearsi Localvi
Korea Group, 1979iv,38
Madarász Retrospective cohortiii, 2008, White 33·1/30·0 (5·9) WHO, 1999vii,39 107 3·6 years (GDM; 0·8)/ WHO, 1999viii,40
et al21 Hungary 8·1 years (non-GDM; 5·1)
Gunderson Prospective cohort, 2007, USA Mixed Matched range 18–30 Obstetric laboratory 2408 Total 20 year follow-up American Diabetes
et al22 reports (72% followed for entire Association, 1997ix/diabetes
time) medication/self report
Vambergue Prospective cohort, 2007, Mixed 27·0 (5·2)/28·8 (5·8) Carpenter and 581xi,xii (175 AGT) 6·75 years (0·8) American Diabetes
et al23 France Coustanx,41 Association, 1997ix
Lee A et al24 Retrospective cohort, 2007, Mixed 30·7 (5·1)/30·5 (4·6) Australian Diabetesxiii,42 6253xiv 2·2 years (GDM),i WHO, 1998viii,40
Australia (pregnancy guidelines) 8·6 years (non-GDM)i
Ferraz et al17 Prospective cohort, 2007, Brazil Non-white 26·9/25·1 WHO, 1999xv,43 178xvi 6·2 years (0·8) WHO, 1999viii,40
Krishnaveni Prospective cohort, 2007, India Non-white Matched age range Carpenter and 524 5 years WHO, 1999viii,40
et al25 Coustanx,41
Morimitsu Prospective cohort, 2007, Brazil Mixed 32/27 (7) American Diabetes 34xviii 16–24 weeks American Diabetes
et al26 Association, 1997xvii,14 Association, 1997ix
Järvelä et al5 Retrospective cohortiii, 2006, White 31·6 (17·7–46·5)/31·3 Finnish Diabetes 870v,xii,xiv 5·7 years (GDM; 1·0–11·6) Medication for T2DM
Finland (18·8–46·0) Associationxix,44 6·1 (non-GDM; 1·5–13·1) linked to databasexx,45
Albareda Prospective cohort, 2003, White 30·7/30·4 Second and third GDM 766xiv 6·16 years (0·05–13·73) WHO, 1998viii,40
et al27 Spain workshop
conferencexxi,46,47
Åberg et al28 Retrospective cohort, 2002, White Matched range 20–45 European Association 290 1 year WHO, 1985xxiii
Sweden for Study of
Diabetesxxii,48
Linné et al16 Retrospective cohort iii, 2002, White 32·6/30·6 Localxxiv 80v,xvi,xxv 15 years Localxxvi
Sweden
Bian et al29 Retrospective cohort, 2000, Non-white 29/29 (23–40) National Diabetes Data 84v,xiv,xviii,xxvii 5–11 years WHO, 1985xxiii
China Group, 1979iv
Ko et al30 Prospective cohort, 1999, Non-white 34·0 (4·1)/34·4 (6·4) Localxxviii 1232v 6 weeks WHO, 1985xxiii
China
Osei et al31 Retrospective cohort, 1998, Non-white 31·3 (2·0)/36·0 (0·9) National Diabetes Data 65xxix 7 years National Diabetes Data
USA Group, 1979iv Group, 1979xxx,49
Damm et al32 Retrospective cohort, 1994, White 30·1/26·7 Localxxxi 298xiv 7·5 yearsi WHO, 1985xxiii
Denmark
Benjamin Retrospective cohort, 1993, Mixed 27·2/26·5 Localxxxii,50 94v,xii,xvi,xxxiii,51 4·8 years (GDM)/ National Diabetes Data
et al33 New Mexico 5·5 years (non-GDM) Group, 1979xxx,49
O’Sullivan34 Prospective cohort, 1991, USA Mixed ·· Localxxxii 943 22–28 years WHO, 1985xxiii
Persson Retrospective cohort, 1991, White 31 (20–46)/30 (16–43) WHO, 1985 xxxiv,51
186 v,xii,xix,xxxv
3–4 years WHO, 1985xxiii
et al35 Sweden

AGT=abnormal glucose tolerance. FPG=fasting plasma glucose. IGT=impaired glucose tolerance. i=median values at follow-up only. ii=includes all individuals diagnosed with diabetes ≥90 days after delivery
living within Ontario, Canada. iii=report is cited as a case-control study in the summary but as a cohort study in the methods. iv=two or more FPG concentrations ≥5·8 mmol/L or 1 h glucose ≥10·6 mmol/L, 2 h
glucose ≥9·2 mmol/L, 3 h glucose ≥8·1 mmol/L after 100 g glucose load. v=matched by age. vi=FPG concentrations ≥7 mmol/L only. vii=FPG concentrations ≥7 mmol/L or 2 h glucose ≥11·1 mmol/L, or both, after
75 g oral glucose load. viii=FPG concentrations ≥7 mmol/L, or 2 h glucose ≥11·1 mmol/L after 75 g glucose load. ix=FPG concentrations ≥7 mmol/L or 2 h glucose ≥11·1 mmol/L, or both, after 75 g glucose load.
x=FPG concentrations ≥5·3 mmol/L or 2 h plasma glucose ≥8·6 mmol/L, or 3 h glucose ≥7·7 mmol/L after 100 g oral glucose load. xi=matched by ethnic origin. xii=matched by parity. xiii=FPG concentrations
≥5·5 mmol/L or 2 h glucose ≥8·0 mmol/L after 75 g glucose load (before Jan 01, 1999, FPG ≥7·8 mmol/L, 1 h glucose ≥9 mmol/L and 2 h glucose ≥7·0 mmol/L after 50 g glucose load). xiv=matched by year of
delivery. xv=FPG concentrations ≥7 mmol/L or 2 h glucose ≥11·1 mmol/L, or both, (group also included gestational impaired glucose tolerance=FPG <7 mmol/L and 2 h glucose 7·8–11·1 mmol/L) after 75 g oral
glucose load. xvi=matched by body-mass index. xvii=two or more FPG concentrations ≥5·3 mmol/L, 1 h glucose ≥10·0 mmol/L, 2 h glucose ≥8·6 mmol/L, 3 h glucose ≥7·8 mmol/L after 100 g glucose load.
xviii=matched by gestational age at study entry. xix=FPG concentrations ≥4·8 mmol/L or 1 h glucose ≥10·0 mmol/L, or 2 h glucose ≥8·7 mmol/L after 75 g oral glucose load. xx=medications obtained from
central drug register with complete population coverage plus questionnaire. xxi=two or more FPG concentrations ≥5·8 mmol/L, 1 h glucose ≥10·6 mmol/L, 2 h glucose ≥9·2 mmol/L, 3 h glucose ≥8·1 mmol/L
after glucose (75 g) load. xxii=FPG concentrations ≥6 mmol/L or 2 h glucose ≥9 mmol/L after 75 g glucose load. xxiii=FPG concentrations ≥7·8 mmol/L, or 2 h glucose ≥11·1 mmol/L after 75 g oral glucose load.
xxiv=2 h glucose concentration ≥9 mmol/L after 75 g glucose load. xxv=matched by waist to hip ratio. xxvi=2 h glucose concentration >10 mmol/L after 75 g glucose load. xxvii=matched by social background.
xxviii=two or more FPG concentrations ≥5·0 mmol/L or 1 h glucose ≥9·5 mmol/L, 2 h glucose ≥8·1 mmol/L, 3 h glucose ≥7·0 mmol/L after 50 g glucose load. xxix=study included a third group of 15 women who
were not included in this meta-analysis. xxx=FPG concentrations ≥7·8 mmol/L or 2 h glucose 11·1 mmol/L after 75 g glucose load. xxxi=two or more venous plasma glucose concentrations >3 SD from the mean
in women without gestational diabetes after 50 g glucose load (0 min: 6·4 mmol/L; 30 min: 10·1 mmol/L; 1 h: 10·1 mmol/L; 90 min: 8·7 mmol/L; 2 h: 7·6 mmol/L; 150 min: 7·6 mmol/L; 3 h: 6·6 mmol/L).
xxxii=fasting venous whole blood glucose concentration ≥5 mmol/L or 2 h venous whole blood glucose ≥8·0 mmol/L or 3 h glucose ≥6·9 mmol/L) after 100 g glucose load. xxxiii=matched by length of follow-up.
xxxiv=FPG concentrations ≥7 mmol/L and 2 h glucose ≥7·8 mmol/L after 75 g oral glucose load. xxxv=matched by prepregnancy weight and weight gain.

Table: Gestational diabetes mellitus (GDM) and development of type 2 diabetes mellitus (T2DM)

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Country T2DM/GDM T2DM/no GDM Relative risk (95% CI)

Feig et al,18 1995–2002 Canada 2874/21 823 6628/637 341 12·66 (12·15–13·19)
Lee H et al,15 1995–97 Korea 71/620 22/868 4·52 (2·83–7·21)
Madarasz et al,21 1995 Hungary 21/68 0/39 24·93 (1·55–400·64)
Gunderson et al,22 1985–206 USA 43/166 150/2242 3·87 (2·87–5·22)
Vambergue et al,23 1992 France 53/295 1/111 19·94 (2·79–142·47)
Lee A et al,24 1971–2003 Australia 405/5470 16/783 3·62 (2·21–5·93)
Ferraz et al17* Brazil 6/70 7/108 1·32 (0·46–3·78)
Krishnaveni et al,25 1997–98 India 13/35 8/489 22·70 (10·09–51·08)
Morimitsu et al,26 1999–2001 Brazil 7/23 0/11 7·50 (0·47–120·11)
Järvelä et al,5 1984–94 Finland 23/435 0/435 47·00 (2·86–771·65)
Albareda et al,27 1966–93 Spain 44/696 0/70 9·07 (0·56–146·25)
Åberg et al,28 1991–99 Sweden 21/229 1/61 5·59 (0·77–40·66)
Linné et al,16 1964–65 Sweden 10/28 0/52 38·38 (2·33–631·74)
Bian et al,29 1964–65 China 15/45 1/39 13·00 (1·80–93·93)
Ko et al,30 1988–95 China 105/801 7/431 8·07 (3·79–17·19)
Osei et al,31 1990–91 USA 10/15 0/35 47·25 (2·95–757·28)
Damm et al,32 1978–85 Denmark 33/241 0/57 16·06 (1·00–258·06)
Benjamin et al,33 1961–88 New Mexico 14/47 3/47 4·67 (1·43–15·21)
O’Sullivan,34 1954–60 and 1962–70 USA 224/615 18/328 6·64 (4·19–10·52)
Persson et al,35 1961–84 Sweden 5/145 0/41 3·16 (0·18–55·76)

Total 3997/31 867 6862/643 588 7·43 (4·79–11·51)

Test for heterogeneity: τ 2 =0·50, χ 2=126·67, df=19 (p<0·0001), l2=85·0% (95%CI 78–90)
Test for overall effect: Z=9·39 (p<0·0001)

0·01 0·1 1 10 100


Decreased risk Increased risk

Figure 2: Risk of type 2 diabetes mellitus (T2DM) after gestational diabetes mellitus (GDM)
x-axis is log scale. Each solid square represents a relative risk. Horizontal lines indicate 95% CIs. df=degrees of freedom. *Dates not available.

association between gestational diabetes and type 2


0·0 diabetes, and the knowledge that many of the risk factors
are the same (ie, a family history of diabetes, raised
0·4
body-mass index, increased age, and Asian and black
ethnic origin), suggest that the two disorders might have
an overlapping cause.4 Results of candidate gene studies,
SE of log risk ratio

0·8 giving support to this hypothesis,52,53 show that frequency


of some alleles associated with the increased risk of
development of type 2 diabetes were increased in women
1·2
who had gestational diabetes. Irrespective of the precise
biological link between these two disorders, the
1·6 development of gestational diabetes might help to identify
women at high risk of developing type 2 diabetes.
Although women who have had gestational diabetes
0·01 0·1 1 10 100 are recommended to have a glucose tolerance test at
Relative risk 6 weeks postpartum, most do not attend.11 The increased
risk of type 2 diabetes reported in this meta-analysis
Figure 3: Funnel plot of 20 cohort studies included in meta-analysis
might help to motivate mothers to attend screening
x-axis is log scale. Dotted line is the summary relative risk (7·43).
programmes, and health-care professionals to increase
In nine5,17,25,28–31,33,35 of 20 studies, none of the women uptake to these programmes or perhaps suggest the best
dropped out and data were not missing. In four time for reassessment. Since the risk of type 2 diabetes
studies,18,22,23,32 633 449 (96%) of 659 164, 1696 (70%) of seems to be maintained for several years, consideration
2408, 713 (71%) of 1009, and 241 (81%) of 298 women were of whether any form of continuous assessment would
followed up. In another study,24 2739 (44%) of 6253 were lead to health gains is important. Women who have had
followed up. In six studies,15,16,21,26,27,34 the dropout rate was gestational diabetes also have increased lipid concentra-
not recorded. tions and blood pressure, and type 2 diabetes is estimated
to confer an equivalent risk of ageing 15 years.54 Early
Discussion identification and treatment of these factors could also
Women who have had gestational diabetes have at least a help to reduce premature cardiovascular and renal
seven-fold increased risk of developing type 2 diabetes diseases in this group of individuals.10
mellitus in the future compared with those who have had We noted heterogeneity in the overall effect estimate and
a normoglycaemic pregnancy. The strength of the did subgroup analyses to determine the potential sources.

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Total number of Relative risk (99% CI) l2 (%; 99% CI) τ2 χ 2 test of
cases of T2DM heterogeneity
(p value)

A
Ethnic origin 0 (0–95) 0 0·78 on 2 df (0·68)
White (7 studies) 158 12·76 (2·31–70·63) 0 (0–80) 0 3·31 on 6 df (0·77)
Non-white (6 studies) 265 7·45 (2·43–22·83) 78 (38–92) 0·76 22·97 on 5 df (0·0003)
Mixed (7 studies) 10436 6·36 (2·06–19·61) 93 (87–97) 0·55 92·20 on 6 df (<0·0001)

Follow-up time 60 (N/A) 0·14 2·49 on 1 df (0·11)


<5 years (8 studies) 698 4·69 (2·84–7·75) 0 (0–77) 0 4·66 on 7 df (0·70)
≥5 years (12 studies) 10161 9·34 (3·42–25·54) 88 (77–93) 0·53 88·10 on 11 df (<0·0001)

Study design 0 (N/A) 0 0·62 on 1 df (0·43)


Prospective (9 studies) 779 6·07 (2·68–13·74) 71 (29–88) 0·28 27·64 on 8 df (0·0005)
Retrospective (11 studies) 10080 9·29 (3·02–28·60) 68 (27–86) 0·46 31·30 on 10 df (0·0005)

Number of incident cases 88 (54–97) 0·05 16·78 on 2 df (0·0002)


<100 (15 case studies) 389 8·71 (3·00–25·31) 52 (0–72) 0·58 29·37 on 14 df (0·009)
100–500 (4 studies) 968 4·88 (2·65–8·97) 55 (0–90) 0·07 6·74 on 3 df (0·08)
>500 (1 study) 9502 12·66 (11·79–13·60) N/A N/A N/A

B
Maternal age 0 (0–92) 0 0·25 on 3 df (0·97)
<30 years (5 studies) 9602 6·67 (1·08–41·16) 81 (14–94) 1·02 20·65 on 4 df (0·0004)
≥30 years (9 studies) 739 6·14 (2·66–14·15) 33 (0–76) 0·14 11·93 on 8 df (0·15)
Age range reported only (4 studies) 478 7·40 (2·03–26·94) 83 (14–95) 0·41 17·50 on 3 df (0·0006)
Not similar* (2 studies) 40 10·97 (0·37–325·68) 0 (N/A) 0 0·14 on 1 df (0·70)

BMI at index pregnancy 42 (0–88) 0·10 3·46 on 2 df (0·18)


<25 kg/m2 (4 studies) 205 8·92 (2·83–28·12) 0 (0–92) 0 0·38 on 3 df (0·94)
25–30 kg/m2 (1 study) 428 3·70 (1·59–8·58) 0 (N/A) 0 0·26 on 1 df (0·61)
Not recorded (15 studies) 10226 7·66 (3·12–18·79) 88 (79–93) 0·52 109·78 on 13 df (<0·0001)

BMI at follow-up 0 (0–92) 0 0·20 on 3 df (0·98)


<25 kg/m2 (5 studies) 424 6·66 (2·29–19·40) 78 (29–93) 0·32 17·98 on 4 df (0·001)
25–30 kg/m2 (3 studies) 105 8·94 0·58–138·54) 64 (0–90) 1·98 11·20 on 4 df (0·02)
≥30 kg/m2 (2 studies) 27 10·42 (0·25–433·97) 56 (N/A) 1·49 2·26 on 1 df (0·13)
Not recorded (10 studies) 10303 8·10 (2·82–23·25) 79 (49–91) 0·36 33·33 on 7 df (<0·0001)

C
GDM criteria 0 (0–80) 0 5·27 on 6 df (0·51)
WHO (3 studies) 39 3·28 (0·17–62·56) 48 (0–90) 1·16 3·87 on 2 df (0·14)
NDDG (4 studies) 163 6·77 (1·61–28·47) 20 (0–93) 0·20 3·75 on 3 df (0·29)
Countrywide guidelines (3 studies) 451 6·54 (0·61–69·89) 40 (0–87) 0·70 3·33 on 2 df (0·19)
Carpenter and Coustan (2 studies) 75 22·27 (6·10–81·25) 0 (N/A) 0 0·01 on 1 df (0·90)
EASD (1 study) 22 5·59 (0·18–172·63) N/A N/A N/A
Local (5 studies) 414 7·03 (3·73–13·25) 0 (0–87) 0 2·40 on 4 df (0·66)
Other† (2 studies) 9695 7·07 (0·95–52·45) 98 (N/A) 0·69 58·89 on 1 df (<0·00001)

T2DM criteria 22 (0–75) 0·05 5·14 on 4 df (0·27)


WHO (11 studies) 950 6·60 (2·58–16·89) 61 (7–83) 0·37 25·45 on 10 df (0·005)
NDDG (2 studies) 27 10·42 (0·25–433·97) 56 (N/A) 1·49 2·26 on 1 df (0·13)
ADA (3 studies) 254 5·46 (1·12–26·69) 29 (0–96) 0·28 2·80 on 2 df (0·25)
Local (2 studies) 103 8·28 (0·32–216·45) 54 (N/A) 1·24 2·18 on 1 df (0·14)
Other† (2 studies) 9525 12·66 (11·79–13·60) 0 (N/A) 0 0·84 on 1 df (0·36)

0·01 0·1 1 10 100


Decreased risk Increased risk

Figure 4: Risk of type 2 diabetes mellitus (T2DM) grouped by study characteristics (A), participant characteristics (B), and diagnostic criteria (C)
x-axis is log scale. Each solid square represents a relative risk. Horizontal lines indicate 99% CIs. ADA=American Diabetes Association. BMI=body-mass index. df=degrees of freedom. EASD=European
Association for Study of Diabetes. GDM=gestational diabetes mellitus. N/A=heterogeneity not applicable because one study analysed. NDDG=National Diabetes Data Group. *Average ages of women
with and without GDM were not similar; therefore effect of maternal age could not be assessed. †Includes databases and obstetric reports (table).

Effect estimates were similar when studies were grouped heterogeneity, which was reduced by exclusion of the
according to patient characteristics, suggesting that much largest study. However, this study was of high quality and
of the heterogeneity was unexplained. The effect estimates resulted in an effect size that was larger, instead of smaller,
reported in studies in which different criteria were used than the estimates from small studies. Although we did
for the diagnosis of gestational diabetes mellitus and type 2 not identify the main sources of heterogeneity of effect
diabetes mellitus were similar. The number of cases of size, a meta-analysis of summary data from reported
type 2 diabetes included in our analysis contributed to the studies has little capacity to do so. These sources could be

www.thelancet.com Vol 373 May 23, 2009 1777


Articles

efficiently assessed in an individual-level meta-analysis Contributors


with existing datasets, or in a new large prospective study LB contributed to protocol design, data extraction, statistical analysis,
and data interpretation. J-PC contributed to statistical analysis and data
that might help to delineate useful features for identi- interpretation. ADH helped with data interpretation. DW contributed to
fication of a mother with gestational diabetes at high risk protocol design, and data extraction and interpretation. All authors
of developing type 2 diabetes. contributed to the writing and revision of this report, and have seen and
We were unable to stratify results according to family approved the final version.
history of diabetes and previous gestational diabetic Conflicts of interest
pregnancy because of the absence of studies that ADH is a member of the editorial board of Drug and Therapeutics
Bulletin and has acted as an adviser to GlaxoSmithKline and London
adequately addressed this issue. With the exception of Genetics. He has received honoraria for speaking at educational
the largest study18—the only study in which women were meetings sponsored by the pharmaceutical industry and has donated all
not analysed according to their late-onset diagnosis of or most of these to charity. The other authors declare that they have no
diabetes (type 1 or 2)—we excluded studies or parts of conflicts of interest.

studies in which women who developed type 1 diabetes Acknowledgments


in later life were identified. Therefore, inclusion of this A proportion of DW’s salary was received by the University College
London/University College London Hospital from the Department of
study might have resulted in an overestimation of the Health’s National Institute for Health Research Biomedical Research
number of women with gestational diabetes who Centre. ADH is a British Heart Foundation Senior Research Fellow
developed type 2 diabetes. However, because type 1 (FS051/125). We thank Reecha Sofat for statistical support.
diabetes is rare compared with type 2 disease and References
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