The Association Between Diabetes Mellitus and the Risk of Latent Tuberculosis Infection: A Systematic Review and Meta-Analysis

Background: The estimated global latent tuberculosis infection (LTBI) burden indicates a large reservoir of population at risk of developing active tuberculosis (TB). Previous studies showed diabetes mellitus (DM) might associate with risk of LTBI, but still controversial. We aimed to systematically assess the association between DM and the risk of LTBI, as well as prediabetes (pre-DM), to provide latest evidence on early screening of LTBI among DM patients and prevention its progress to active TB. Methods: We searched PubMed, Embase, Cochrane Library and Web of Science before 16 March 2021. Observational studies reporting the number of LTBI and non-LTBI individuals with and without diabetes were included. Random-effects or fixed-effects models were used to estimate the pooled effect by risk ratios (RRs) and odds ratios (ORs) and its 95% confidence interval (CI). Findings: 19 studies involving 4,054,950 participants were included. The pooled effect of association between DM and the risk of LTBI was significant (for cohort studies, RR=1·62, 95% CI: 1·02 – 2·56; for cross-sectional studies, OR=1·57, 95% CI: 1·32 – 1·87). The pooled OR was higher in studies of healthcare-workers (5·27, 95% CI: 1·52 – 8·20), refugees (2.88, 95% CI: 1·93 – 4·29), sample size of 1000 to 5000 (1·99, 95% CI: 1·49 – 2·66), and male accounted for less than 40% (2·36, 95% CI: 1·19 – 4·66). Pre-DM was also associated with LTBI (OR=1·36, 95% CI: 1·01 – 1·84). Interpretation: DM might increase the risk of LTBI by about 60%, compared with individuals without DM. Our findings highlight the importance of LTBI screening among DM patients. More studies are needed to explore appropriate strategies and tools for targeted LTBI screening among DM patients. Funding Information: This study was funded by the National Key Research and Development Project of China [grant numbers 2020YFC0846300, 2020YFC0849500]; the National Science and Technology Key Projects on Prevention and Treatment of Major infectious disease of China [grant number 2020ZX10001002]; and the National Natural Science Foundation of China [grant numbers 71934002]. Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: All analyses in our study were based on previous published studies, thus no ethical approval is required.