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Evidence summaries

Gestational Diabetes Mellitus and Future Risk of Diabetes

Gestational diabetes mellitus increases the future risk of diabetes up to 10-fold. Level of evidence: "A"

The quality of evidence is upgraded by very large magnitude of effect.

Use glucose tests for screening of women who have had gestational diabetes, if early diagnosis of type 2 diabetes is wanted.

The recommendation is strong because of high cost-effectiveness (high number of positive screens relative to the number of people screened). The recommendation attaches a relatively high value on the potential benefit of early detection and treatment of type 2 diabetes.

Summary

A meta-analysis 11 included 20 studies with a total of 1 332 373 individuals. The overall relative risk for type 2 diabetes (T2D) was almost 10 times higher in women with previous gestational diabetes mellitus (GDM) than in healthy controls (9.51, 95% CI 7.14 to 12.67, P<0.001). In populations of women with previous GDM, the cumulative incidence of T2D was 16.46% (95% CI 16.16% to 16.77%) in women of mixed ethnicity, 15.58% (13.30% to 17.86%) in a predominantly non-white population, and 9.91% (9.39% to 10.42%) in a white population. Meta-regression analyses showed that the study effect size was not significantly associated with mean study age, body mass index, publication year, and length of follow-up.

A meta-analysis 5 identified 20 cohort studies in which women who had developed T2D after GDM and included 675 455 women and 10 859 type 2 diabetic events. Women with GDM had an increased risk of developing T2D compared with those who had a normoglycaemic pregnancy (RR 7.43, 95% CI 4.79-11.51). Although the largest study (n=659 164; 9502 cases of T2D) had the largest RR (12.6, 95% CI 12.15-13.19), RRs were generally consistent among the subgroups assessed.

In an another retrospective cohort study 4, 185 416 pregnant women who had a (glucose challenge test) GCT or (oral glucose tolerance test) OGTT were followed in Israel. Subsequent diagnosis of T2D was ascertained by using an automated patient registry. 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 T2D 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. GDM was associated with nearly an 8-fold higher risk of postpartum diabetes after adjusting for important confounders, such as socioeconomic status and BMI. 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 T2D.

A meta-analysis 6 assessing the future risk of T2D after GDM included 39 studies with a total of 95 750 women. BMI (RR 1.95, 95% CI 1.60 to 2.31), family history of diabetes (RR 1.70, 95% CI 1.47 to 1.9), non-white ethnicity (RR 1.49, 95% CI 1.14 to 1.94) and advanced maternal age (RR 1.20, 95% CI 1.09 to 1.34) were associated with future risk of T2D. There was an increase in risk with early diagnosis of GDM (RR 2.13, 95% CI 1.52 to 3.56), raised fasting glucose (RR 3.57, 95% CI 2.98 to 4.04), increased HbA1c (RR 2.56, 95% CI 2.00 to 3.17) and use of insulin (RR 3.66, 95% CI 2.78 to 4.82). Multiparity (RR 1.23, 95% CI 1.01 to 1.50), hypertensive disorders in pregnancy (RR 1.38, 95% CI 1.32 to 1.45) and preterm delivery (RR 1.81, 95% CI 1.35 to 2.43) were associated with future diabetes. Gestational weight gain, macrosomia in the offspring or breastfeeding did not increase the risk.

A cohort study 7 with a 23 year follow-up included 391 women with GDM diagnosed by an OGTT or the use of insulin treatment during pregnancy, and 391 age- and parity-matched control participants. T1D developed (5.7%) during the first 7 years after GDM pregnancy and was predictable at a 2 h OGTT value of 11.9 mmol/l during pregnancy (receiver operating characteristic analysis: AUC 0.91, sensitivity 76.5%, specificity 96.0%). T2D increased linearly to 50.4% by the end of the follow-up period and was moderately predictable with fasting glucose (AUC 0.69, sensitivity 63.5%, specificity 68.2%) at a level of 5.1 mmol/l.

A cross-sectional study 8 determined the proportion of women who progress to type 2 diabetes mellitus (T2DM) and associated risk factors 5 to 6 years after hyperglycaemia first detected in pregnancy (includes GDM) in Cape Town, South Africa. Each participant had a 75 g OGTT; anthropometric measurements and a survey were administered. Mean age was 37.2 years (SD 6.0). Of the 498 participants 220 were followed-up for 5 - 6 years. 48 % (95% CI 41.2 to 54.4) progressed to T2DM, 5.5% (95% CI 3.1 to 9.4) had impaired fasting glucose, and 10.5% (95% CI 7.0 to 15.3) had impaired glucose tolerance. When GDM was categorized post hoc according to WHO 2013 guidelines, progression in the diabetes in pregnancy group was 81% (95% CI 70.2 to 89.0) and 31.3% (95% CI 24.4 to 39.3) in the GDM category. Factors associated with risk of progression to T2DM were; waist circumference (odds ratios [OR] 1.1, 95% CI 1.0 to 1.1, p = 0.007), hip circumference (OR 0.9, 95% CI 0.8 to 1.0, p = 0.001), and BMI (OR 1.1, 95% CI 1.0 to1.3, p = 0.001), and at baseline: insulin (OR 25.8, 95% CI 3.9 to 171.4, p = 0.001) and oral hypoglycaemic treatment during HFDP (OR 4.1, 95% CI 1.3 to 12.9, p = 0.018), fasting (OR 2.7, 95% CI 1.5 to 4.8, p = 0.001), and oral glucose tolerance test 2-hour glucose concentration at HFDP diagnosis (OR 4.3, 95% CI 2.4 to 7.7, p < 0.001). There was no control group.

A meta-analysis 9 included 30 studies with 2 626 905 pregnant women. Women with prior GDM had 7.76-fold (95% CI 5.10 to 11.81) unadjusted pooled risk of diabetes as compared with women without GDM, whilst the adjusted risk was 17.92-fold (16.96 to 18.94). The adjusted ORs of GDM for diabetes among women at <3, ≥3 - <6 and ≥6 - <10 years after GDM were 5.37 (3.51 to 9.34), 16.55 (16.08 to 17.04) and 8.20 (4.53 to 14.86), respectively.

Another meta-analysis 10 included 43 studies, evaluating 4 923 571 pregnant women of which 5.8% (284 312) had a history of GDM. Five studies used IADPSG criteria (n=6174, 1314 with GDM). The overall pooled relative risk (RR) for postpartum T2DM was 7.42 (95% CI 5.99 to 9.19) and the RR for postpartum T2DM with IADPSG criteria was 6.45 (95% CI 4.74 to 8.77) compared to the RR of 9.08 (95% CI 6.96 to 11.85; p = 0.17) for postpartum T2DM based on other diagnostic criteria. The RR for postpartum IGT was 2.45 (95% CI 1.92 to 3.13), independent of the criteria used.

Clinical comments

Note

Date of latest search:2020-09-14

    References

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    • Rayanagoudar G, Hashi AA, Zamora J et al. Quantification of the type 2 diabetes risk in women with gestational diabetes: a systematic review and meta-analysis of 95,750 women. Diabetologia 2016;59(7):1403-1411. [PubMed]
    • Auvinen AM, Luiro K, Jokelainen J et al. Type 1 and type 2 diabetes after gestational diabetes: a 23 year cohort study. Diabetologia 2020;63(10):2123-2128. [PubMed]
    • Chivese T, Norris SA, Levitt NS. Progression to type 2 diabetes mellitus and associated risk factors after hyperglycemia first detected in pregnancy: A cross-sectional study in Cape Town, South Africa. PLoS Med 2019;16(9):e1002865. [PubMed]
    • Song C, Lyu Y, Li C et al. Long-term risk of diabetes in women at varying durations after gestational diabetes: a systematic review and meta-analysis with more than 2 million women. Obes Rev 2018;19(3):421-429. [PubMed]
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    • Vounzoulaki E, Khunti K, Abner SC et al. Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis. BMJ 2020;369():m1361.[PubMed]

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