Causal relationship between diabetes and urinary tract infections: A Mendelian randomization study

Area of Science:

• Genetics
• Epidemiology
• Infectious Diseases

Background:

• Diabetes mellitus (DM) is linked to infections, but its specific role in urinary tract infections (UTIs) is debated.
• Understanding the causal link between DM types and UTIs is crucial for public health.

Purpose of the Study:

• To investigate the causal relationship between type 1 DM (T1DM) and type 2 DM (T2DM) and three common UTIs: pyelonephritis, cystitis, and urethritis.
• To utilize Mendelian randomization (MR) to establish causality, accounting for potential confounders.

Main Methods:

• A two-sample Mendelian randomization (MR) study design was employed.
• Inverse variance weighted (IVW) method was primary; MR-Egger and weighted median methods were used for sensitivity analysis.
• Heterogeneity, pleiotropy, and leave-one-out tests were conducted for result validation. Multivariate MR adjusted for BMI and HbA1c.

Main Results:

• Mendelian randomization revealed a significant causal relationship between T1DM and T2DM and an increased risk of pyelonephritis.
• This causal link persisted after adjusting for body mass index and glycosylated hemoglobin.
• No significant causal associations were found between T1DM or T2DM and cystitis or urethritis.

Conclusions:

• Type 1 DM and type 2 DM are causally associated with the development of pyelonephritis in European ancestry populations.
• The study did not find evidence for a causal link between T1DM or T2DM and cystitis or urethritis.
• These findings clarify the specific relationship between diabetes and UTI subtypes.