Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 8:17:1725-1737.
doi: 10.2147/IJWH.S517371. eCollection 2025.

Causal Relationship Between Type 2 Diabetes Mellitus and Preeclampsia: A Bidirectional Two-Sample Mendelian Randomized Study

Xuwen Song  1 , Yikang Wang  2 , Pengsheng Li  3 , Yafei Wang  4 , Xinghui Wen  4 , Qingwen Nie  1 , Wanlu An  1 , Huan Wang  1 , Fang He  1
Affiliations

Causal Relationship Between Type 2 Diabetes Mellitus and Preeclampsia: A Bidirectional Two-Sample Mendelian Randomized Study

Xuwen Song et al. Int J Womens Health. .

Abstract

Background: Observational epidemiologic investigations into the link between diabetes mellitus and preeclampsia (PE) have been conducted, but genetic evidence is still lacking. We utilized a two-sample Mendelian randomization (MR) analysis to shed light on the potential influence of type 2 diabetes mellitus (T2DM) on PE at the genetic prediction level.

Methods: We carried out a two-sample bidirectional MR analysis, utilizing genetic variants associated with T2DM (N=461,920) and PE (N=219,817) from the largest available genome-wide association studies. Using inverse variance weighting (IVW) and five validated approaches-MR-Egger, MR-RAPS, ConMix, weighted median, and weighted mode-we derived a potential causal association between T2DM and PE. The relationship between PE and T2DM was explored using reverse MR analysis.

Results: The two-sample MR analysis indicated a causal link between T2DM and PE, with an odds ratio of 1.10 (95% CI, 1.02-1.18; P=0.01). The weighted mode method yielded an odds ratio of 1.22 (95% CI, 1.06-1.40; P=0.019), and the weighted median method produced an odds ratio of 1.19 (95% CI, 1.04-1.36; P=0.022). However, no significant association was detected in the MR-Egger analysis. Heterogeneity was noted in the analysis of T2DM and PE, but no significant horizontal pleiotropy was observed. The results of the reverse MR analysis indicated no significant causal association between PE and T2DM.

Conclusion: For the first time, MR analysis showed a positive causal link from T2DM to PE, but not vice versa. The limited number of SNPs in reverse analysis may affect reliability. Future studies should use more instrumental variables to strengthen findings. Further experiments are also needed to explore underlying mechanisms.

Keywords: causal effect; genome-wide association study; preeclampsia; type 2 diabetes mellitus.

PubMed Disclaimer

Conflict of interest statement

The authors assert that the research was conducted free from any commercial or financial interests that might be considered a potential conflict of interest.

Figures

Figure 1
Figure 1
Overview of the design of the MR study on T2DM and PE.
Figure 2
Figure 2
MR analysis of the causal relationship between T2DM and PE.
Figure 3
Figure 3
Scatter plots for the causal association between T2DM and PE.
Figure 4
Figure 4
Leave-one-out plots for the causal association between T2DM and PE.
Figure 5
Figure 5
Funnel plots of the casual relationship of T2DM and PE.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Dimitriadis E, Rolnik DL, Zhou W, et al. Pre-eclampsia. Nat Rev Dis Primers. 2023;9(1):8. doi: 10.1038/s41572-023-00417-6 - DOI - PubMed
    1. Reddy M, Fenn S, Rolnik DL, et al. The impact of the definition of preeclampsia on disease diagnosis and outcomes: a retrospective cohort study. Am J Obstet Gynecol. 2021;224(2):217.e1–217.e11. doi: 10.1016/j.ajog.2020.08.019 - DOI - PubMed
    1. Cnattingius S, Lindam A, Persson M. Risks of asphyxia-related neonatal complications in offspring of mothers with type 1 or type 2 diabetes: the impact of maternal overweight and obesity. Diabetologia. 2017;60(7):1244–1251. doi: 10.1007/s00125-017-4279-2 - DOI - PMC - PubMed
    1. Chappell LC, Cluver CA, Kingdom J, Tong S. Pre-eclampsia. Lancet. 2021;398(10297):341–354. doi: 10.1016/S0140-6736(20)32335-7 - DOI - PubMed
    1. Webster K, Fishburn S, Maresh M, Findlay SC, Chappell LC. Diagnosis and management of hypertension in pregnancy: summary of updated NICE guidance. BMJ. 2019;366:l5119. doi: 10.1136/bmj.l5119 - DOI - PubMed

LinkOut - more resources