REVIEW URRENT C OPINION
Interventions to modify the progression to type 2 diabetes mellitus in women with gestational diabetes: a systematic review of literature Suzanna Morton a, Samantha Kirkwood b, and Shakila Thangaratinam b,c
Purpose of review Gestational diabetes mellitus (GDM) increases the lifetime risk of developing type 2 diabetes mellitus (T2DM) in the mother. We undertook a systematic review to assess the effectiveness of interventions that delay or prevent the onset of T2DM in women with previous gestational diabetes. Recent findings Diet and lifestyle interventions show differing effects on women with GDM and their long-term risk of T2DM. Pharmacological interventions, such as metformin, appear to have a beneficial role. Breastfeeding may have a protective role by reducing the risk of progression to T2DM. The findings were limited by the small number of heterogeneous studies that varied in their population, intervention, outcome and duration of follow-up. Summary Women with GDM should be informed about the future risk of T2DM and the potential benefit with lifestyle interventions. Further studies are needed prior to routine use of metformin as a preventive strategy for T2DM in women with GDM. Keywords gestational diabetes mellitus, interventions, type 2 diabetes mellitus
INTRODUCTION Gestational diabetes mellitus (GDM) is glucose intolerance first detected or diagnosed during pregnancy [1]. It affects 1.75–4.4% of pregnancies in the United Kingdom [1] and up to 7% of pregnancies in the United States [2] and incidence is increasing globally [3]. The rapid rise in global obesity combined with poor diet, sedentary lifestyle and older parity contribute to this increase in GDM. GDM is associated with maternal and fetal complications in pregnancy, and in the long term, significantly increases the lifetime risk of progression to type 2 diabetes mellitus (T2DM) in the mother. About 15–60% [4] of women with GDM may go on to develop T2DM within 5–15 years after their index pregnancy. Women with pregnancies complicated by GDM have a 7.4-fold increased risk of developing T2DM compared with women who had normoglycaemic pregnancies [5]. T2DM is a major health burden, especially when not diagnosed early, with increased incidence of cardiovascular disease, peripheral vascular disease, neuropathy, retinopathy and nephropathy in affected individuals [6]. Interventions that successfully prevent or delay the onset of T2DM in women with GDM have the www.co-obgyn.com
potential to improve their long-term health and reduce the burden of morbidity associated with diabetes. In the nonpregnant population, interventions such as lifestyle, behavioural and pharmacological methods have been shown to reduce the progression to T2DM [7,8]. We undertook a systematic review of literature to assess the effectiveness of various interventions that delay or arrest the progression from gestational diabetes to T2DM.
METHODS We undertook a literature search in the following electronic databases: Medline (1946–2014), Embase (1974–2014), Maternity and Infant Care (1971– 2014), CINAHL (1981–2014) and Cochrane Library a Whittington Hospital, Whittington Health, bWomen’s Health Unit, Royal London Hospital, Barts Health NHS Trust and cWomen’s Health Research Unit, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
Correspondence to Dr Suzanna Morton, Whittington Hospital, Magdala Avenue, London N19 5NF, UK. Tel: 020 72723070; e-mail: [email protected] Curr Opin Obstet Gynecol 2014, 26:476–486 DOI:10.1097/GCO.0000000000000127 Volume 26 Number 6 December 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Interventions to modify progression to T2DM in women with GDM: a systematic review Morton et al.
KEY POINTS Diet and lifestyle interventions have the potential to reduce progression to T2DM in women with GDM. Lactation may have a protective effect by preventing progression to T2DM. The effectiveness and side-effects profile of pharmacological agents, such as metformin, on postnatal mothers in preventing T2DM needs further evaluation.
(1972–2014). We used the search terms of ‘gestational diabetes,’ ‘pregnancy induced diabetes’ or ‘pregnancy diabetes mellitus’ and ‘type 2-diabetes prevention’ (and other terminology for type 2 diabetes) as well as specific factors associated with a reduction in the progression to type 2 diabetes including diet, lifestyle changes, exercise, lactation, and pharmacological (hypoglycaemic) agents (including metformin, antidiabetic agent, antihyperglycaemic or hypoglycaemic or antidiabetic, thiazolidinediones or rosiglitazone or pioglitazone or rosiglitazone). Language restrictions were not applied. Two reviewers independently reviewed the citations (S. Morton and S. Kirkwood) to identify all relevant primary articles. All reference lists from the articles obtained and relevant reviews were hand searched to obtain additional studies. Disagreements in study selection were resolved by consensus. Articles were excluded if the population studied was not entirely composed of women with gestational diabetes, the end point did not include the development of T2DM, absence of any original data or abstract publication only. Two independent reviewers (S. Morton and S. Kirkwood) extracted data from the relevant articles. Any discrepancies were resolved by discussion with a third reviewer. The quality of randomized trials was assessed by risk of bias instrument and observational studies by looking at whether the study was prospective or retrospective, had used an appropriate population group, intervention and outcome were appropriate, whether confounders had been accounted for and duration of follow-up. The data were extracted in 2 2 or 2 1 tables. If metaanalysis was not possible to estimate pooled estimates, we undertook narrative reporting of the results for the individual studies.
RESULTS We identified 941 citations from the literature searches and we selected 49 articles for further
evaluation. The study identification and selection are summarized in Fig. 1. Eleven primary studies (n ¼ 10 968 women) were included in the review [9 ,10–13,14 ,15–19]. Of these, six [9 ,10–12, 15,16] were randomized controlled trials (RCTs) and four [13,14 ,18,19] were comparative cohort studies, and one [17] was an open-label observational study. Table 1 provides a summary of the characteristics of the included studies. Half the randomized trials (three out of six) had adequate randomization, and a third (two out of six) had adequate concealment. The outcomes were adequately reported in half the trials (three out of six) with no selective reporting in three of the six studies. Four of the five observational studies were prospective. The population was appropriate in all but one study. The intervention and outcomes were appropriate, and the follow-up was adequate in all studies. Table 2 provides details of the quality assessment of individual studies. &&
&&
&&
&&
Citations identified from electronic databases (n = 941)
Articles excluded after evaluation of abstracts (n = 892)
Full text articles retrieved for detailed evaluation (n = 49)
Articles excluded (n = 38) -
-
Review articles (n = 13) Duplicate data (n = 2) Abstracts from meetings (n = 2) Commentaries (n = 2) Population studied not exclusively women with GDM and no subgroup analysis to look at GDM (n = 10) Outcome not development of Type 2 DM (n = 7) Did not control for other confounding variables (n = 1) Follow up period too short (n = 1)
Studies included in review (n = 11)
FIGURE 1. Study identification process in the systematic review of interventions to prevent type 2 diabetes after gestational diabetes. GDM, gestational diabetes mellitus; T2DM, type 2 diabetes mellitus.
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477
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478
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2008 RCT
2006 Open label Women who completed observational TRIPOD study who did study not have diabetes at the end of TRIPOD
Xiang et al. [17]
Ratner et al. [11]
2002 Double-blind RCT
Buchanan et al. [15]
Women with history of GDM and current impaired glucose tolerance
Hispanic women with GDM in the past 4 years
Latino women with GDM and impaired glucose tolerance
1996 RCT
Berkowitz et al. [16]
Population
Year
Author
Design
3 years
3.5 years
30 months
12 weeks
Follow-up
350
86
266
42
Metformin or intensive lifestyle
Pioglitazone 45 mg/day for 3 years
Troglitazone 400 mg
Troglitazone 200 mg or 400 mg
Number of women Intervention
Placebo and cohort of parous women with IGT who had not had GDM
No control
Placebo
Placebo
Comparison
Table 1. Characteristics of the primary studies on interventions to modify progression to type 2 diabetes after gestational diabetes
Metformin gave 50% RR compared with placebo in progression to diabetes (P ¼ 0.006) and intensive lifestyle achieved a 53% RR (P ¼ 0.002). History of GDM conferred greater incidence of progression from GDM to T2DM (15.2 cases per 100 person-years compared with 8.9 P < 0.05)
Annual incidence of diabetes 5.2% during treatment, 4.6% during entire observation period – lower than rate of 12.1% per year observed in placebo arm of TRIPOD. Diabetes incidence rates lowest in the third of women with the greatest reduction of insulin output
Protection from diabetes associated with increased insulin sensitivity and reduced insulin output. Protection from diabetes persisted for at least 8 months after drug stopped
Lower cumulative incidence of diabetes in troglitazone group – HR 0.45 (95% CI 0.25–0.83)
Dose-dependent increase in insulin sensitivity (IS). IS 88þ/22 in 400 mg/day group and 4þ/ 14 in placebo (P ¼ 0.01)
No significant difference with fasting glucose or glucose tolerance
Outcome
Women’s health
Volume 26 Number 6 December 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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2012 Prospective Participants with prior observational GDM from the Nurses cohort Health Study II
Tobias et al. [13]
Shek 2013 RCT && et al. [9 ]
2013 RCT
Shyam et al. [12]
Women (95% Chinese) with history of GDM in index pregnancy, diagnosed with IGT
Asian women aged 20–40 with previous GDM plus one of BMI>23, waist >80 cm, IGT or family history of T2DM
2014 Prospective Women with previous observational GDM age 25–44 cohort
Bao et al. && [14 ]
36 months
14 years
6 months
16 years
450
4413
77
4554
Advice on diet and exercise with individual counselling to intervention group
Dietary patterns: alternate Mediterranean diet (aMED), dietary approaches to hypertension (DASH) and alternate healthy eating index (aHEI)
Conventional healthy dietary recommendation (CHDR) or CHDR PLUS low glycaemic (LGI) dietary advice
Physical activity (4th quartiles)
No intervention
1st and 4th quartiles for adherence to dietary patterns. Adjustment for BMI was made.
N/A
1st quartile for total physical activity and sedentary behaviour
(Continued )
Cumulative rate of DM at 3 years: 15% in intervention and 19% in control groups but not statistically significant. Significantly fewer women >40 years in intervention group developed T2DM ¼ 9.3 vs. 22.47% in control group (P ¼ 0.018)
491(11.1%) cases of T2DM observed. All three dietary patterns inversely correlated with T2DM risk Independent of BMI, a 1-unit IQR in score adherence to: 1) aMED was assoc. with 15% lower risk of T2DM, HR 0.84 (95% CI 0.73–0.96), 2) DASH was assoc. with 10% lower risk but this was not statistically significant and 3) aHEI was assoc. with 17% lower risk, HR 0.77 (CI 0.64–0.93, P ¼ 0.007)
Significant increase in CHDR þ 0.8 (IQR:2) P ¼ 0.01
2HPP in LGI group 0.2 mmol/ l(IQR: 2.8) P ¼ 0.96
After 6 months, significant reductions observed in body weight, BMI and waist-to-hip ratio in LGI group No significant change in median
RR 0.5 (95% CI 0.38–0.65 P < 0.001) when comparing top with bottom quartile after controlling for other variables including BMI
Significant and inverse correlation between physical activity and diabetes risk in women with previous GDM
Interventions to modify progression to T2DM in women with GDM: a systematic review Morton et al.
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479
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480
2005 Retrospective Parous women living in observational USA aged 25–42 with cohort study history of GDM participating in Nurses Health Study II
2012 Prospective cohort study
Stuebe et al. [18]
Zeigler et al. [19]
www.co-obgyn.com German women with GDM
Women with GDM
1999 RCT
Population
Wein et al. [10]
Design
Year
Author
Table 1 (Continued)
19 years
12 years
51 month median follow-up
Follow-up
304 (of which 201 breastfed)
266
200
Breastfeeding
Breast feeding
Intensive dietary and exercise advice with 3-monthly telephone follow-up by dietician
Number of women Intervention
Women who did not breastfeed
N/A
Routine advice on diet and exercise
Comparison
Women who breastfed >3 months had lowest diabetes risk: 15 year risk 42% (CI 28.9–55.1) (34.8% if exclusively breastfeeding) vs. no breastfeeding or < 3 month duration of breastfeeding risk of T2DM 72% (CI 60.5–84.7) P ¼ 0.0002. Beneficial risk of lactation was sustained over time
Breastfeeding in autoantibody negative women was associated with a delay in diabetes development – median 12.2 vs. 2.2 years P ¼ 0.012
Lactation had no effect on diabetes risk in GDM women with covariate HR of 0.96 (CI 0.84–1.09) per additional year of lactation
No significant difference between intervention and control groups in prevalence of T2DM and IGT Lactation had no effect on diabetes risk in GDM group per additional year of lactation HR 0.96 (CI 0.84–1.09)
Outcome
Women’s health
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Interventions to modify progression to T2DM in women with GDM: a systematic review Morton et al. Table 2. Quality assessment of the included studies in the systematic review of interventions to prevent progression to type 2 diabetes in women with gestational diabetes mellitus (a) Randomized trials Was randomization adequately generated?
Was the randomization concealed?
Was the study blinded?
Were outcomes adequately assessed?
Are the reports free from selective outcome reporting?
Was the study free of other problems that could put it at risk of bias?
Shek et al. [9 ]
Yes
Yes
No
Yes
Yes
Yes
Wein et al. [10]
Unclear
Unclear
No
Yes
Yes
Yes
Ratner et al. [11]
Yes
No
Yes for drug, no for lifestyle intervention
Unclear
Unclear
Yes
Shyam et al. [12]
Yes
Yes
No
No
Unclear
Yes
Buchanan et al. [15]
Unclear
Unclear
Yes
Yes
Yes
Yes
Berkowitz et al. [16]
Unclear
Unclear
Yes
No
No
Yes
Study &&
(b) Observational studies
Design
Appropriate population
Appropriate intervention
Appropriate outcome
Accounted for confounders
Duration of follow-up adequate
Tobias et al. [13]
Prospective
Yes
Yes
Yes
Yes
Yes
Bao et al. [14 ]
Prospective
Yes
Yes
Yes
Yes
Yes
Xiang et al. [17]
Prospective
No
Yes
Yes
Unclear
Yes
Steube et al. [18]
Retrospective
Yes
Yes
Yes
Yes
Yes
Zeigler et al. [19]
Prospective
Yes
Yes
Yes
Yes
Yes
Study
&&
DIET AND LIFESTYLE INTERVENTIONS Six studies (three RCT, three observational and cohort) evaluated the effect of diet and lifestyle in women with GDM on the development of T2DM [9 ,10–13,14 ]. The findings are provided in Table 3. &&
&&
Randomized evidence Two RCTs assessed the combined effects of exercise and diet [9 ,10]. Shek et al. [9 ] (n ¼ 450) studied the effects of the combined intervention on women with previous GDM and impaired glucose tolerance in the postpartum period. A dietician offered advice on diet and physical activity. The intervention was provided after randomization on seven occasions over a 3-year follow-up period. Women in the intervention arm monitored their food intake and physical activity for 5 days before each follow-up. There was a trend towards a reduction in the risk of T2DM by 3 years that was not statistically significant [relative risk (RR) 0.77, 95% confidence interval (CI) 0.51–1.16]. Subgroup analysis showed a significant difference (RR 0.35, 95% CI 0.17–0.75, P ¼ 0.018) between the groups based on maternal age, with fewer women aged over 40 progressing to type 2 &&
&&
diabetes (9.3%) compared with the control arm (22.5%). The randomized study by Wein et al. [10] (n ¼ 200 women) on women with previous GDM and impaired glucose tolerance in the postnatal period evaluated the effects of advice on regular exercise and healthy diet. The intervention group had regular telephone contact with a dietician every 3 months. There were no significant differences between the groups for T2DM at 51 months follow-up (RR 0.63, 95% CI 0.35–1.14). An intervention on the basis of intensive lifestyle therapy was evaluated in a randomized study by Ratner et al. [11] involving 239 women with previous GDM. The goal of the intervention was to achieve and maintain weight reduction of 7% of initial body weight through diet and exercise. Participants were given a 16-lesson curriculum in order to help them achieve these goals. There was a 53.4% reduction in the incidence of T2DM over a 3-year follow-up period compared with the 122 women in the control group (P < 0.05) with a number needed to treat of 5.3 women to prevent one case of T2DM. A low glycaemic index diet [12] (n ¼ 77) in Asian women with previous GDM and an additional risk
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481
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482
www.co-obgyn.com 200 450 77
Wein et al. [10] 1999
Shek et al. [9 ] 2014
Shyam et al. [12] 2013
350 42
Ratner et al. [11] 2008
Berkowitz et al. [16] 1996
88 22 40 22@
Troglitazone 400 mg
@
7.8/100 person-years
5.4% annual incidence
Median 0.2 mmol/l (IQR 2.8)
33/225
6.1% annual incidence
7.4/100 person-years
Intervention group risk/estimate
Troglitazone 200 mg
Metformin
Troglitazone 400 mg
Low-glycaemic index diet
Diet and exercise
Diet and exercise
Intensive lifestyle
Intervention
4 14%
@
15.2/100 person-years
12.1% annual incidence
Median 0.8 mmol/l (IQR 2.0)
43/225
7.3% annual incidence
15.2/100 person-years
Control group risk/estimate
@
Insulin sensitivity
T2DM
T2DM
Change in blood glucose 2 h post-75 g glucose load from baseline
T2DM
T2DM
T2DM
Outcome
P ¼ 0.03
RR 0.47; P ¼ 0.002a
HR 0.45 (95% CI 0.25–0.83) P ¼ 0.009
P ¼ 0.025
RR 0.77 (95% CI 0.51–1.16)
RR 0.63 (95% CI 0.35–1.14) P ¼ 0.12
RR 0.50; P ¼ 0.006a
Effect estimate
264
Ziegler et al. [19] 2012
6.9/1000 person-years
aHEI diet
Lactation
15 year risk 42% (95% CI 28.9–55.1)
N/A
7.5 per 1000 person-years
DASH diet
Lactation
7.9 per 1000 person-years
108 /1138
Intervention group risk
A Med diet
Physical activity
Intervention
15 year risk 72% (95% CI 60.5–84.7)
N/A
11.6/1000 person-years
12.1 per 1000 person-years
11.2 per 1000 person-years
221/1140
Control group risk
T2DM
T2DM
T2DM
T2DM
Outcome
HR 0.55 (95% CI 0.35–0.85) P ¼ 0.000d
HR 0.96 (95% CI 0.84–1.09)c
HR 0.77(95% CI 0.64–0.93)
HR 0.86 (95% CI 0.73–1.03) P ¼ 0.1
HR 0.84 (95% CI0.73–0.96)b
RR 0.5 (95% CI 0.38–0.65); P < 0.001a
Effect estimate
comparing most active and least active quartiles bfor 1-unit increase in IQR cper additional year of lactation dcomparing lactation for >3 months with
Interventions to modify the progression to type 2 diabetes mellitus in women with gestational diabetes: a systematic review of literature Suzanna Morton a, Samantha Kirkwood b, and Shakila Thangaratinam b,c
Purpose of review Gestational diabetes mellitus (GDM) increases the lifetime risk of developing type 2 diabetes mellitus (T2DM) in the mother. We undertook a systematic review to assess the effectiveness of interventions that delay or prevent the onset of T2DM in women with previous gestational diabetes. Recent findings Diet and lifestyle interventions show differing effects on women with GDM and their long-term risk of T2DM. Pharmacological interventions, such as metformin, appear to have a beneficial role. Breastfeeding may have a protective role by reducing the risk of progression to T2DM. The findings were limited by the small number of heterogeneous studies that varied in their population, intervention, outcome and duration of follow-up. Summary Women with GDM should be informed about the future risk of T2DM and the potential benefit with lifestyle interventions. Further studies are needed prior to routine use of metformin as a preventive strategy for T2DM in women with GDM. Keywords gestational diabetes mellitus, interventions, type 2 diabetes mellitus
INTRODUCTION Gestational diabetes mellitus (GDM) is glucose intolerance first detected or diagnosed during pregnancy [1]. It affects 1.75–4.4% of pregnancies in the United Kingdom [1] and up to 7% of pregnancies in the United States [2] and incidence is increasing globally [3]. The rapid rise in global obesity combined with poor diet, sedentary lifestyle and older parity contribute to this increase in GDM. GDM is associated with maternal and fetal complications in pregnancy, and in the long term, significantly increases the lifetime risk of progression to type 2 diabetes mellitus (T2DM) in the mother. About 15–60% [4] of women with GDM may go on to develop T2DM within 5–15 years after their index pregnancy. Women with pregnancies complicated by GDM have a 7.4-fold increased risk of developing T2DM compared with women who had normoglycaemic pregnancies [5]. T2DM is a major health burden, especially when not diagnosed early, with increased incidence of cardiovascular disease, peripheral vascular disease, neuropathy, retinopathy and nephropathy in affected individuals [6]. Interventions that successfully prevent or delay the onset of T2DM in women with GDM have the www.co-obgyn.com
potential to improve their long-term health and reduce the burden of morbidity associated with diabetes. In the nonpregnant population, interventions such as lifestyle, behavioural and pharmacological methods have been shown to reduce the progression to T2DM [7,8]. We undertook a systematic review of literature to assess the effectiveness of various interventions that delay or arrest the progression from gestational diabetes to T2DM.
METHODS We undertook a literature search in the following electronic databases: Medline (1946–2014), Embase (1974–2014), Maternity and Infant Care (1971– 2014), CINAHL (1981–2014) and Cochrane Library a Whittington Hospital, Whittington Health, bWomen’s Health Unit, Royal London Hospital, Barts Health NHS Trust and cWomen’s Health Research Unit, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
Correspondence to Dr Suzanna Morton, Whittington Hospital, Magdala Avenue, London N19 5NF, UK. Tel: 020 72723070; e-mail: [email protected] Curr Opin Obstet Gynecol 2014, 26:476–486 DOI:10.1097/GCO.0000000000000127 Volume 26 Number 6 December 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Interventions to modify progression to T2DM in women with GDM: a systematic review Morton et al.
KEY POINTS Diet and lifestyle interventions have the potential to reduce progression to T2DM in women with GDM. Lactation may have a protective effect by preventing progression to T2DM. The effectiveness and side-effects profile of pharmacological agents, such as metformin, on postnatal mothers in preventing T2DM needs further evaluation.
(1972–2014). We used the search terms of ‘gestational diabetes,’ ‘pregnancy induced diabetes’ or ‘pregnancy diabetes mellitus’ and ‘type 2-diabetes prevention’ (and other terminology for type 2 diabetes) as well as specific factors associated with a reduction in the progression to type 2 diabetes including diet, lifestyle changes, exercise, lactation, and pharmacological (hypoglycaemic) agents (including metformin, antidiabetic agent, antihyperglycaemic or hypoglycaemic or antidiabetic, thiazolidinediones or rosiglitazone or pioglitazone or rosiglitazone). Language restrictions were not applied. Two reviewers independently reviewed the citations (S. Morton and S. Kirkwood) to identify all relevant primary articles. All reference lists from the articles obtained and relevant reviews were hand searched to obtain additional studies. Disagreements in study selection were resolved by consensus. Articles were excluded if the population studied was not entirely composed of women with gestational diabetes, the end point did not include the development of T2DM, absence of any original data or abstract publication only. Two independent reviewers (S. Morton and S. Kirkwood) extracted data from the relevant articles. Any discrepancies were resolved by discussion with a third reviewer. The quality of randomized trials was assessed by risk of bias instrument and observational studies by looking at whether the study was prospective or retrospective, had used an appropriate population group, intervention and outcome were appropriate, whether confounders had been accounted for and duration of follow-up. The data were extracted in 2 2 or 2 1 tables. If metaanalysis was not possible to estimate pooled estimates, we undertook narrative reporting of the results for the individual studies.
RESULTS We identified 941 citations from the literature searches and we selected 49 articles for further
evaluation. The study identification and selection are summarized in Fig. 1. Eleven primary studies (n ¼ 10 968 women) were included in the review [9 ,10–13,14 ,15–19]. Of these, six [9 ,10–12, 15,16] were randomized controlled trials (RCTs) and four [13,14 ,18,19] were comparative cohort studies, and one [17] was an open-label observational study. Table 1 provides a summary of the characteristics of the included studies. Half the randomized trials (three out of six) had adequate randomization, and a third (two out of six) had adequate concealment. The outcomes were adequately reported in half the trials (three out of six) with no selective reporting in three of the six studies. Four of the five observational studies were prospective. The population was appropriate in all but one study. The intervention and outcomes were appropriate, and the follow-up was adequate in all studies. Table 2 provides details of the quality assessment of individual studies. &&
&&
&&
&&
Citations identified from electronic databases (n = 941)
Articles excluded after evaluation of abstracts (n = 892)
Full text articles retrieved for detailed evaluation (n = 49)
Articles excluded (n = 38) -
-
Review articles (n = 13) Duplicate data (n = 2) Abstracts from meetings (n = 2) Commentaries (n = 2) Population studied not exclusively women with GDM and no subgroup analysis to look at GDM (n = 10) Outcome not development of Type 2 DM (n = 7) Did not control for other confounding variables (n = 1) Follow up period too short (n = 1)
Studies included in review (n = 11)
FIGURE 1. Study identification process in the systematic review of interventions to prevent type 2 diabetes after gestational diabetes. GDM, gestational diabetes mellitus; T2DM, type 2 diabetes mellitus.
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478
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2008 RCT
2006 Open label Women who completed observational TRIPOD study who did study not have diabetes at the end of TRIPOD
Xiang et al. [17]
Ratner et al. [11]
2002 Double-blind RCT
Buchanan et al. [15]
Women with history of GDM and current impaired glucose tolerance
Hispanic women with GDM in the past 4 years
Latino women with GDM and impaired glucose tolerance
1996 RCT
Berkowitz et al. [16]
Population
Year
Author
Design
3 years
3.5 years
30 months
12 weeks
Follow-up
350
86
266
42
Metformin or intensive lifestyle
Pioglitazone 45 mg/day for 3 years
Troglitazone 400 mg
Troglitazone 200 mg or 400 mg
Number of women Intervention
Placebo and cohort of parous women with IGT who had not had GDM
No control
Placebo
Placebo
Comparison
Table 1. Characteristics of the primary studies on interventions to modify progression to type 2 diabetes after gestational diabetes
Metformin gave 50% RR compared with placebo in progression to diabetes (P ¼ 0.006) and intensive lifestyle achieved a 53% RR (P ¼ 0.002). History of GDM conferred greater incidence of progression from GDM to T2DM (15.2 cases per 100 person-years compared with 8.9 P < 0.05)
Annual incidence of diabetes 5.2% during treatment, 4.6% during entire observation period – lower than rate of 12.1% per year observed in placebo arm of TRIPOD. Diabetes incidence rates lowest in the third of women with the greatest reduction of insulin output
Protection from diabetes associated with increased insulin sensitivity and reduced insulin output. Protection from diabetes persisted for at least 8 months after drug stopped
Lower cumulative incidence of diabetes in troglitazone group – HR 0.45 (95% CI 0.25–0.83)
Dose-dependent increase in insulin sensitivity (IS). IS 88þ/22 in 400 mg/day group and 4þ/ 14 in placebo (P ¼ 0.01)
No significant difference with fasting glucose or glucose tolerance
Outcome
Women’s health
Volume 26 Number 6 December 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
1040-872X ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
2012 Prospective Participants with prior observational GDM from the Nurses cohort Health Study II
Tobias et al. [13]
Shek 2013 RCT && et al. [9 ]
2013 RCT
Shyam et al. [12]
Women (95% Chinese) with history of GDM in index pregnancy, diagnosed with IGT
Asian women aged 20–40 with previous GDM plus one of BMI>23, waist >80 cm, IGT or family history of T2DM
2014 Prospective Women with previous observational GDM age 25–44 cohort
Bao et al. && [14 ]
36 months
14 years
6 months
16 years
450
4413
77
4554
Advice on diet and exercise with individual counselling to intervention group
Dietary patterns: alternate Mediterranean diet (aMED), dietary approaches to hypertension (DASH) and alternate healthy eating index (aHEI)
Conventional healthy dietary recommendation (CHDR) or CHDR PLUS low glycaemic (LGI) dietary advice
Physical activity (4th quartiles)
No intervention
1st and 4th quartiles for adherence to dietary patterns. Adjustment for BMI was made.
N/A
1st quartile for total physical activity and sedentary behaviour
(Continued )
Cumulative rate of DM at 3 years: 15% in intervention and 19% in control groups but not statistically significant. Significantly fewer women >40 years in intervention group developed T2DM ¼ 9.3 vs. 22.47% in control group (P ¼ 0.018)
491(11.1%) cases of T2DM observed. All three dietary patterns inversely correlated with T2DM risk Independent of BMI, a 1-unit IQR in score adherence to: 1) aMED was assoc. with 15% lower risk of T2DM, HR 0.84 (95% CI 0.73–0.96), 2) DASH was assoc. with 10% lower risk but this was not statistically significant and 3) aHEI was assoc. with 17% lower risk, HR 0.77 (CI 0.64–0.93, P ¼ 0.007)
Significant increase in CHDR þ 0.8 (IQR:2) P ¼ 0.01
2HPP in LGI group 0.2 mmol/ l(IQR: 2.8) P ¼ 0.96
After 6 months, significant reductions observed in body weight, BMI and waist-to-hip ratio in LGI group No significant change in median
RR 0.5 (95% CI 0.38–0.65 P < 0.001) when comparing top with bottom quartile after controlling for other variables including BMI
Significant and inverse correlation between physical activity and diabetes risk in women with previous GDM
Interventions to modify progression to T2DM in women with GDM: a systematic review Morton et al.
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2005 Retrospective Parous women living in observational USA aged 25–42 with cohort study history of GDM participating in Nurses Health Study II
2012 Prospective cohort study
Stuebe et al. [18]
Zeigler et al. [19]
www.co-obgyn.com German women with GDM
Women with GDM
1999 RCT
Population
Wein et al. [10]
Design
Year
Author
Table 1 (Continued)
19 years
12 years
51 month median follow-up
Follow-up
304 (of which 201 breastfed)
266
200
Breastfeeding
Breast feeding
Intensive dietary and exercise advice with 3-monthly telephone follow-up by dietician
Number of women Intervention
Women who did not breastfeed
N/A
Routine advice on diet and exercise
Comparison
Women who breastfed >3 months had lowest diabetes risk: 15 year risk 42% (CI 28.9–55.1) (34.8% if exclusively breastfeeding) vs. no breastfeeding or < 3 month duration of breastfeeding risk of T2DM 72% (CI 60.5–84.7) P ¼ 0.0002. Beneficial risk of lactation was sustained over time
Breastfeeding in autoantibody negative women was associated with a delay in diabetes development – median 12.2 vs. 2.2 years P ¼ 0.012
Lactation had no effect on diabetes risk in GDM women with covariate HR of 0.96 (CI 0.84–1.09) per additional year of lactation
No significant difference between intervention and control groups in prevalence of T2DM and IGT Lactation had no effect on diabetes risk in GDM group per additional year of lactation HR 0.96 (CI 0.84–1.09)
Outcome
Women’s health
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Interventions to modify progression to T2DM in women with GDM: a systematic review Morton et al. Table 2. Quality assessment of the included studies in the systematic review of interventions to prevent progression to type 2 diabetes in women with gestational diabetes mellitus (a) Randomized trials Was randomization adequately generated?
Was the randomization concealed?
Was the study blinded?
Were outcomes adequately assessed?
Are the reports free from selective outcome reporting?
Was the study free of other problems that could put it at risk of bias?
Shek et al. [9 ]
Yes
Yes
No
Yes
Yes
Yes
Wein et al. [10]
Unclear
Unclear
No
Yes
Yes
Yes
Ratner et al. [11]
Yes
No
Yes for drug, no for lifestyle intervention
Unclear
Unclear
Yes
Shyam et al. [12]
Yes
Yes
No
No
Unclear
Yes
Buchanan et al. [15]
Unclear
Unclear
Yes
Yes
Yes
Yes
Berkowitz et al. [16]
Unclear
Unclear
Yes
No
No
Yes
Study &&
(b) Observational studies
Design
Appropriate population
Appropriate intervention
Appropriate outcome
Accounted for confounders
Duration of follow-up adequate
Tobias et al. [13]
Prospective
Yes
Yes
Yes
Yes
Yes
Bao et al. [14 ]
Prospective
Yes
Yes
Yes
Yes
Yes
Xiang et al. [17]
Prospective
No
Yes
Yes
Unclear
Yes
Steube et al. [18]
Retrospective
Yes
Yes
Yes
Yes
Yes
Zeigler et al. [19]
Prospective
Yes
Yes
Yes
Yes
Yes
Study
&&
DIET AND LIFESTYLE INTERVENTIONS Six studies (three RCT, three observational and cohort) evaluated the effect of diet and lifestyle in women with GDM on the development of T2DM [9 ,10–13,14 ]. The findings are provided in Table 3. &&
&&
Randomized evidence Two RCTs assessed the combined effects of exercise and diet [9 ,10]. Shek et al. [9 ] (n ¼ 450) studied the effects of the combined intervention on women with previous GDM and impaired glucose tolerance in the postpartum period. A dietician offered advice on diet and physical activity. The intervention was provided after randomization on seven occasions over a 3-year follow-up period. Women in the intervention arm monitored their food intake and physical activity for 5 days before each follow-up. There was a trend towards a reduction in the risk of T2DM by 3 years that was not statistically significant [relative risk (RR) 0.77, 95% confidence interval (CI) 0.51–1.16]. Subgroup analysis showed a significant difference (RR 0.35, 95% CI 0.17–0.75, P ¼ 0.018) between the groups based on maternal age, with fewer women aged over 40 progressing to type 2 &&
&&
diabetes (9.3%) compared with the control arm (22.5%). The randomized study by Wein et al. [10] (n ¼ 200 women) on women with previous GDM and impaired glucose tolerance in the postnatal period evaluated the effects of advice on regular exercise and healthy diet. The intervention group had regular telephone contact with a dietician every 3 months. There were no significant differences between the groups for T2DM at 51 months follow-up (RR 0.63, 95% CI 0.35–1.14). An intervention on the basis of intensive lifestyle therapy was evaluated in a randomized study by Ratner et al. [11] involving 239 women with previous GDM. The goal of the intervention was to achieve and maintain weight reduction of 7% of initial body weight through diet and exercise. Participants were given a 16-lesson curriculum in order to help them achieve these goals. There was a 53.4% reduction in the incidence of T2DM over a 3-year follow-up period compared with the 122 women in the control group (P < 0.05) with a number needed to treat of 5.3 women to prevent one case of T2DM. A low glycaemic index diet [12] (n ¼ 77) in Asian women with previous GDM and an additional risk
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www.co-obgyn.com 200 450 77
Wein et al. [10] 1999
Shek et al. [9 ] 2014
Shyam et al. [12] 2013
350 42
Ratner et al. [11] 2008
Berkowitz et al. [16] 1996
88 22 40 22@
Troglitazone 400 mg
@
7.8/100 person-years
5.4% annual incidence
Median 0.2 mmol/l (IQR 2.8)
33/225
6.1% annual incidence
7.4/100 person-years
Intervention group risk/estimate
Troglitazone 200 mg
Metformin
Troglitazone 400 mg
Low-glycaemic index diet
Diet and exercise
Diet and exercise
Intensive lifestyle
Intervention
4 14%
@
15.2/100 person-years
12.1% annual incidence
Median 0.8 mmol/l (IQR 2.0)
43/225
7.3% annual incidence
15.2/100 person-years
Control group risk/estimate
@
Insulin sensitivity
T2DM
T2DM
Change in blood glucose 2 h post-75 g glucose load from baseline
T2DM
T2DM
T2DM
Outcome
P ¼ 0.03
RR 0.47; P ¼ 0.002a
HR 0.45 (95% CI 0.25–0.83) P ¼ 0.009
P ¼ 0.025
RR 0.77 (95% CI 0.51–1.16)
RR 0.63 (95% CI 0.35–1.14) P ¼ 0.12
RR 0.50; P ¼ 0.006a
Effect estimate
264
Ziegler et al. [19] 2012
6.9/1000 person-years
aHEI diet
Lactation
15 year risk 42% (95% CI 28.9–55.1)
N/A
7.5 per 1000 person-years
DASH diet
Lactation
7.9 per 1000 person-years
108 /1138
Intervention group risk
A Med diet
Physical activity
Intervention
15 year risk 72% (95% CI 60.5–84.7)
N/A
11.6/1000 person-years
12.1 per 1000 person-years
11.2 per 1000 person-years
221/1140
Control group risk
T2DM
T2DM
T2DM
T2DM
Outcome
HR 0.55 (95% CI 0.35–0.85) P ¼ 0.000d
HR 0.96 (95% CI 0.84–1.09)c
HR 0.77(95% CI 0.64–0.93)
HR 0.86 (95% CI 0.73–1.03) P ¼ 0.1
HR 0.84 (95% CI0.73–0.96)b
RR 0.5 (95% CI 0.38–0.65); P < 0.001a
Effect estimate
comparing most active and least active quartiles bfor 1-unit increase in IQR cper additional year of lactation dcomparing lactation for >3 months with
