Type 2 diabetes, glucose, insulin, BMI, and ischemic stroke subtypes: Mendelian randomization study

Area of Science:

• Genetics
• Neurology
• Metabolic Diseases

Background:

• Type 2 diabetes mellitus (T2D) is a growing global health concern.
• Ischemic stroke is a leading cause of disability and mortality worldwide.
• Understanding the causal relationship between T2D and stroke subtypes is crucial for prevention and treatment.

Purpose of the Study:

• To investigate the potential causal associations between T2D, fasting glucose, fasting insulin, and body mass index (BMI) with specific ischemic stroke subtypes using a Mendelian randomization (MR) approach.
• To differentiate the effects of these risk factors on large artery stroke, small vessel stroke, and cardioembolic stroke.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) design.
• Utilized summary statistics from large genome-wide association studies (GWAS) for T2D, fasting glucose, fasting insulin, BMI, and ischemic stroke subtypes.
• Applied inverse-variance weighted (IVW) and weighted median methods for primary analysis, with MR-Egger regression to assess pleiotropy.

Main Results:

• Genetically predicted T2D showed a significant causal association with large artery stroke (OR 1.28) and small vessel stroke (OR 1.21).
• The association between T2D and large artery stroke remained consistent in sensitivity analyses.
• No statistically significant causal associations were found for genetically predicted fasting glucose, fasting insulin, or BMI with any ischemic stroke subtype.

Conclusions:

• This study provides robust evidence supporting a causal link between type 2 diabetes mellitus and large artery stroke.
• The findings highlight the importance of T2D management in reducing the risk of specific ischemic stroke subtypes.