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. 2024 Jan 13;23(1):31.
doi: 10.1186/s12933-023-02117-7.

Type 1 diabetes, its complications, and non-ischemic cardiomyopathy: a mendelian randomization study of European ancestry

Yunyue Zhao #  1 , Enxi Quan #  2 , Tao Zeng #  3 , Zhuoshan Huang  1 , Yanting Luo  1 , Long Peng  1 , Suhua Li  1 , Jinlai Liu  1 , Yutian Chong  4 , Hong Cao  5
Affiliations

Type 1 diabetes, its complications, and non-ischemic cardiomyopathy: a mendelian randomization study of European ancestry

Yunyue Zhao et al. Cardiovasc Diabetol. .

Abstract

Background: Type 1 diabetes (T1D) is a significant risk factor for a range of cardiovascular diseases. Nonetheless, the causal relationship between T1D and non-ischemic cardiomyopathy (NICM) remains to be elucidated. Furthermore, the mechanisms responsible for the progression from T1D to NICM have not been definitively characterized.

Objective: The aim of this study was to conduct a Mendelian randomization (MR) study to investigate the causal effects of T1D and its complications on the development of NICM. Additionally, this study aimed to conduct a mediation analysis to identify potential mediators within this correlation.

Methods: Genetic variants were used as instrumental variables for T1D. The summary data for T1D were obtained from two genome-wide association study datasets. The summary data for T1D with complications and NICM were obtained from the Finnish database. Two-sample MR, multivariable MR and mediation MR were conducted in this study.

Results: The study revealed a causal association between T1D, T1D with complications, and NICM (with odds ratios of 1.02, 95% CI 1.01-1.04, p = 1.17e-04 and 1.03, 95% CI 1.01-1.05, p = 3.15e-3). Even after adjusting for confounding factors such as body mass index and hypertension, T1D remained statistically significant (with odds ratio of 1.02, 95% CI 1.01-1.04, p = 1.35e-4). Mediation analysis indicated that monokine induced by gamma interferon may play a mediating role in the pathogenesis of T1D-NICM (mediation effect indicated by odds ratio of 1.005, 95% CI 1.001-1.01, p = 4.9e-2).

Conclusion: The study demonstrates a causal relationship between T1D, its complications, and NICM. Additionally, monokine induced by gamma interferon may act as a potential mediator in the pathogenesis of T1D-NICM.

Keywords: Mediation analysis; Mendelian randomization; Non-ischemic cardiomyopathy; Type 1 diabetes; Type 1 diabetes with complication.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Study design
Fig. 2
Fig. 2
Genetically predicted type 1 diabetes and its complications: associations with the non-ischemic cardiomyopathy. IVW (Inverse Variance Weighted), H (Heterogeneity), P (Pleiotropy), CI (Confidence Interval), OR (Odds Ratio), p < 0.05 was considered statistically significant. The FDR-corrected results of the p-values (IVW) in each sub-group remained consistent with the uncorrected results
Fig. 3
Fig. 3
Genetically predicted association of T1D and its complications: associations with the non-ischemic cardiomyopathy after adjusting for confounders. CI (Confidence Interval), OR (Odds Ratio), p < 0.05 was considered statistically significant
Fig. 4
Fig. 4
Mediation analysis. CI (Confidence Interval), OR (Odds Ratio), p < 0.05 was considered statistically significant. After applying FDR correction, the p-value for the correlation between MIG and NICM was determined to be 0.25
See this image and copyright information in PMC

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