Causality between serum uric acid and diabetic microvascular complications - a mendelian randomization study

Area of Science:

• Genetics and Epidemiology
• Metabolic Diseases
• Renal Medicine

Background:

• Diabetic microvascular complications pose a significant health burden.
• The role of serum uric acid (SUA) in these complications requires clarification.
• Mendelian randomization (MR) offers a robust method to investigate causal relationships.

Purpose of the Study:

• To determine if elevated serum uric acid (SUA) causally influences diabetic microvascular complications.
• To utilize a two-sample Mendelian randomization (MR) approach for robust causal inference.
• To specifically examine the associations with diabetic nephropathy, retinopathy, and neuropathy.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) design using genome-wide association study (GWAS) summary statistics.
• Utilized data for SUA from the IEU OPEN GWAS PROJECT and for diabetic microvascular complications from the FinnGen consortium.
• Applied inverse variance weighting (IVW) for primary analysis, with MR-Egger, weighted median, and MR-PRESSO for sensitivity analyses.

Main Results:

• A significant causal relationship was observed between genetically predicted higher SUA and diabetic nephropathy (OR=1.32, p=0.008).
• Consistent results were found for the association between type 2 diabetes mellitus (T2DM) and renal complications.
• No significant causal relationships were detected between genetically predicted SUA and diabetic retinopathy (p=0.249) or diabetic neuropathy (p=0.549).

Conclusions:

• This MR study provides evidence for a causal link between elevated serum uric acid (SUA) and diabetic nephropathy.
• The findings suggest that SUA is a potential causal factor for kidney complications in diabetes.
• No causal association was found between SUA and diabetic retinopathy or neuropathy.