No Casual Relationship Between T2DM and the Risk of Infectious Diseases: A Two-Sample Mendelian Randomization Study

Background: In epidemiological studies, it has been proven that the occurrence of type 2 diabetes mellitus (T2DM) is related to an increased risk of infectious diseases. However, it is still unclear whether the relationship is casual.

Methods: We employed a two-sample Mendelian randomization (MR) to clarify the causal effect of T2DM on high-frequency infectious diseases: sepsis, skin and soft tissue infections (SSTIs), urinary tract infections (UTIs), pneumonia, and genito-urinary infection (GUI) in pregnancy. And then, we analyzed the genome-wide association study (GWAS) meta-analysis of European-descent individuals and conducted T2DM-related single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) that were associated with genome-wide significance (p < 5 × 10^-8). MR estimates were obtained using the inverse variance-weighted (IVW), the MR-Egger regression, the simple mode (SM), weighted median, and weighted mode.

Results: The UK Biobank (UKB) cohort (n > 500,000) provided data for GWASs on infectious diseases. MR analysis showed little evidence of a causal relationship of T2DM with five mentioned infections' (sepsis, SSTI, UTI, pneumonia, and GUI in pregnancy) susceptibility [odds ratio (OR) = 0.99999, p = 0.916; OR = 0.99986, p = 0.233; OR = 0.99973, p = 0.224; OR = 0.99997, p = 0.686; OR, 1.00002, p = 0.766]. Sensitivity analysis showed similar results, indicating the robustness of causality. There were no heterogeneity and pleiotropic bias.

Conclusion: T2DM would not be causally associated with high-frequency infectious diseases (including sepsis, SSTI, UTI, pneumonia, and GUI in pregnancy).