Causal association between type 2 diabetes mellitus and acute suppurative otitis media: insights from a univariate and multivariate Mendelian randomization study

Abstract

Background: Type 2 diabetes mellitus (T2DM) and hearing loss (HL) constitute significant public health challenges worldwide. Recently, the association between T2DM and HL has aroused attention. However, possible residual confounding factors and other biases inherent to observational study designs make this association undetermined. In this study, we performed univariate and multivariable Mendelian Randomization (MR) analysis to elucidate the causal association between T2DM and common hearing disorders that lead to HL.

Methods: Our study employed univariate and multivariable MR analyses, with the Inverse Variance Weighted method as the primary approach to assessing the potential causal association between T2DM and hearing disorders. We selected 164 and 9 genetic variants representing T2DM from the NHGRI-EBI and DIAGRAM consortium, respectively. Summary-level data for 10 hearing disorders were obtained from over 500,000 participants in the FinnGen consortium and MRC-IEU. Sensitivity analysis revealed no significant heterogeneity of instrumental variables or pleiotropy was detected.

Results: In univariate MR analysis, genetically predicted T2DM from both sources was associated with an increased risk of acute suppurative otitis media (ASOM) (In NHGRI-EBI: OR = 1.07, 95% CI: 1.02-1.13, P = 0.012; In DIAGRAM: OR = 1.14, 95% CI: 1.02-1.26, P = 0.016). Multivariable MR analysis, adjusting for genetically predicted sleep duration, alcohol consumption, body mass index, and smoking, either individually or collectively, maintained these associations. Sensitivity analyses confirmed the robustness of the results.

Conclusion: T2DM was associated with an increased risk of ASOM. Strict glycemic control is essential for the minimization of the effects of T2DM on ASOM.

Keywords: Mendelian randomization (MR); acute suppurative otitis media (ASOM); causal relationship; hearing loss (HL); type 2 diabetes mellitus (T2DM).

Figure 1

Overall design of the Mendelian randomization analysis. NHGRI-EBI, National Human Genome Research Institute-European Bioinformatics Institute; DIAGRAM, DIAbetes Genetics Replication and Meta-analysis; SNPs, single-nucleotide polymorphisms; MR, mendelian randomization; IVW, inverse-variance weighted; IVW-FE, fixed-effect IVW; IVW-RE, random-effect IVW; OR, odds ratios.

Figure 2

Associations between genetically predicted T2DM and hearing disorders based on the IVW approach. OR, odds ratio; CI, indicates confidence interval.

Figure 3

Multivariable MR analysis: Assessing the impact of T2DM on hearing disorders with adjustments for sleep, alcohol consumption, body mass index, and smoking. OR, odds ratio; CI, indicates confidence interval.