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30.04.2024 | Original Article

Differential ischemic stroke risk linked to novel subtypes of type 2 diabetes: insights from a Mendelian randomization analysis

verfasst von: Zhichao Ruan, Jinxi Zhao

Erschienen in: Endocrine

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Abstract

Purpose

This study employs a two-sample Mendelian randomization (MR) approach to investigate the variation in ischemic stroke risk across novel subtypes of adult-onset type 2 diabetes.

Methods

Leveraging pooled genome-wide association study (GWAS) data from the Swedish ANDIS cohort, we explored the association of four newly identified type 2 diabetes subtypes—severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD)—with ischemic stroke risk. The outcome data for ischemic stroke and its three subtypes (large artery, cardioembolic, and small vessel stroke) were sourced from the MEGASTROKE Consortium. Our analysis applied multiple MR methods, focusing on the inverse-variance weighted (IVW) technique, complemented by thorough sensitivity analyses to examine heterogeneity and potential horizontal pleiotropy.

Results

Our findings reveal a significant causal relationship between the SIDD subtype and small vessel stroke (OR = 1.06, 95% CI: 1.01–1.11, p = 0.025), while no causal associations were observed for SIRD with any stroke subtype. MOD was causally linked to small vessel stroke (OR = 1.07, 95% CI: 1.02–1.12, p = 0.004) and large artery stroke (OR = 1.07, 95% CI: 1.01–1.13, p = 0.015). Similarly, MARD showed a causal relationship with small vessel stroke (OR = 1.09, 95% CI: 1.03–1.16, p = 0.006) and overall ischemic stroke risk (OR = 1.04, 95% CI: 1.01–1.08, p = 0.010).

Conclusions

Our study highlights distinct causal links between specific type 2 diabetes subtypes and ischemic stroke risks, emphasizing the importance of subtype-specific prevention and treatment strategies.

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Titel: Differential ischemic stroke risk linked to novel subtypes of type 2 diabetes: insights from a Mendelian randomization analysis
verfasst von: Zhichao Ruan
Jinxi Zhao
Publikationsdatum: 30.04.2024
Verlag: Springer US
Erschienen in: Endocrine
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-024-03842-z

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