Beruflich Dokumente
Kultur Dokumente
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.
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)
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)
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)
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.
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)
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)
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)
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
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