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Background <p>Women with a history of gestational diabetes mellitus (GDM) have a substantial 20–50% risk of developing diabetes postpartum. Understanding the precise mechanisms by which lifestyle interventions prevent diabetes is crucial for optimizing clinical care. This study aimed to quantify the extent to which weight change mediates the observed 46% reduction in postpartum diabetes risk achieved by an intensive lifestyle intervention in women with prior GDM.</p> Methods <p>This secondary mediation analysis utilized data from the Tianjin GDM Prevention Program (NCT01554358), a large-scale, 4.5-year randomized controlled trial conducted in China. A total of 1180 women with a recent history of GDM diagnosed according to the 1999 WHO criteria (mean age 32.4 ± 3.50 years; mean BMI 23.9 ± 3.83 kg/m<sup>2</sup>) were randomized to either an intensive lifestyle intervention (<i>n</i> = 592) or usual care (<i>n</i> = 588) 1–5 years postpartum. Body weight indices (including weight, body mass index (BMI), waist circumference, and body fat percentage) and diabetes status were assessed annually. Cox regression models combined with mediation analysis were employed to estimate the proportion of the intervention’s effect mediated by candidate factors.</p> Results <p>Weight reduction demonstrated a continuous, dose-dependent association with a lower incidence of postpartum diabetes, without evidence of a threshold effect. Overall, changes in weight indices mediated 13.0–18.8% of the intervention’s protective effect. This mediation proportion was significantly higher among women who were overweight at baseline, accounting for 24.3–34.7% of the intervention’s benefit. Within this overweight subgroup, changes in waist circumference and body fat individually accounted for over 30% of the total mediated effect.</p> Conclusions <p>Weight loss is a quantifiable and clinically relevant, though partial, mechanism by which lifestyle intervention reduces postpartum diabetes risk, particularly in overweight women with a history of GDM. These findings underscore the importance of continuous monitoring and management of even modest weight changes as a key component of diabetes prevention strategies for this high-risk population.</p> Trial registration <p>NCT01554358. Retrospectively registered clinical trial.</p>

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Weight change mediates the effect of lifestyle intervention on postpartum diabetes in women with prior gestational diabetes: a secondary analysis of a randomized clinical trial

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  • 发表日期：

    2026年1月21日

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  • Weiqin Li,
  • Huikun Liu,
  • Lingyan Feng,
  • Leishen Wang,
  • Shuang Zhang,
  • Wei Li,
  • Gongshu Liu,
  • Junhong Leng,
  • Yun Shen,
  • Ru Gao,
  • Yeyi Zhu,
  • Xilin Yang,
  • Zhijie Yu,
  • Gang Hu

摘要

Background

Women with a history of gestational diabetes mellitus (GDM) have a substantial 20–50% risk of developing diabetes postpartum. Understanding the precise mechanisms by which lifestyle interventions prevent diabetes is crucial for optimizing clinical care. This study aimed to quantify the extent to which weight change mediates the observed 46% reduction in postpartum diabetes risk achieved by an intensive lifestyle intervention in women with prior GDM.

Methods

This secondary mediation analysis utilized data from the Tianjin GDM Prevention Program (NCT01554358), a large-scale, 4.5-year randomized controlled trial conducted in China. A total of 1180 women with a recent history of GDM diagnosed according to the 1999 WHO criteria (mean age 32.4 ± 3.50 years; mean BMI 23.9 ± 3.83 kg/m2) were randomized to either an intensive lifestyle intervention (n = 592) or usual care (n = 588) 1–5 years postpartum. Body weight indices (including weight, body mass index (BMI), waist circumference, and body fat percentage) and diabetes status were assessed annually. Cox regression models combined with mediation analysis were employed to estimate the proportion of the intervention’s effect mediated by candidate factors.

Results

Weight reduction demonstrated a continuous, dose-dependent association with a lower incidence of postpartum diabetes, without evidence of a threshold effect. Overall, changes in weight indices mediated 13.0–18.8% of the intervention’s protective effect. This mediation proportion was significantly higher among women who were overweight at baseline, accounting for 24.3–34.7% of the intervention’s benefit. Within this overweight subgroup, changes in waist circumference and body fat individually accounted for over 30% of the total mediated effect.

Conclusions

Weight loss is a quantifiable and clinically relevant, though partial, mechanism by which lifestyle intervention reduces postpartum diabetes risk, particularly in overweight women with a history of GDM. These findings underscore the importance of continuous monitoring and management of even modest weight changes as a key component of diabetes prevention strategies for this high-risk population.

Trial registration

NCT01554358. Retrospectively registered clinical trial.