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Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model

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Causality between diabetes and membranous nephropathy: Mendelian randomization.

Zhihang Su¹, Ziqi Luo², Di Wu¹

¹Department of Nephrology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, 3002 Sungang West Road, Shenzhen, 518000, China.

Clinical and Experimental Nephrology

|October 7, 2024

Summary

This Mendelian randomization study found that various types of diabetes, including type 2, gestational, and type 1 diabetes, increase the risk of membranous nephropathy (MN). The research clarifies the causal link between diabetes and MN.

Keywords:

Diabetes Membranous nephropathy Mendelian randomization Meta-analysis

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Area of Science:

Nephrology
Endocrinology
Genetics

Background:

The relationship between diabetes mellitus and membranous nephropathy (MN) requires further clarification.
This study investigates the causal link between multiple diabetes subtypes and MN.

Purpose of the Study:

To evaluate the causal effect of various diabetes types on the risk of developing membranous nephropathy (MN).
To summarize evidence from a Mendelian randomization (MR) study to understand the diabetes-MN association.

Main Methods:

Utilized genome-wide association study (GWAS) data for MN and diabetes-related traits (fasting glucose, insulin, HbA1c) from large cohorts.
Employed Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, and MR-PRESSO methods for Mendelian randomization analysis.
Conducted reverse MR analysis and meta-analysis to confirm findings and assess heterogeneity and pleiotropy.

Main Results:

Established a causal link where type 2 diabetes, gestational diabetes, type 1 diabetes (with/without complications), maternal diabetes, and insulin use increase MN risk.
Found no significant association between genetically predicted fasting insulin, fasting blood glucose, or HbA1c levels and MN risk.
Confirmed no significant heterogeneity, horizontal pleiotropy, or reverse causality.

Conclusions:

Mendelian randomization analysis confirms associations between multiple diabetes subtypes and membranous nephropathy.
Provides enhanced understanding of the pathogenic mechanisms linking diabetes and MN.