Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies

Abstract

Background: Several studies have suggested that diabetes mellitus (DM) increases the risk of active tuberculosis (TB). The rising prevalence of DM in TB-endemic areas may adversely affect TB control. We conducted a systematic review and a meta-analysis of observational studies assessing the association of DM and TB in order to summarize the existing evidence and to assess methodological quality of the studies.

Methods and findings: We searched the PubMed and EMBASE databases to identify observational studies that had reported an age-adjusted quantitative estimate of the association between DM and active TB disease. The search yielded 13 observational studies (n = 1,786,212 participants) with 17,698 TB cases. Random effects meta-analysis of cohort studies showed that DM was associated with an increased risk of TB (relative risk = 3.11, 95% CI 2.27-4.26). Case-control studies were heterogeneous and odds ratios ranged from 1.16 to 7.83. Subgroup analyses showed that effect estimates were higher in non-North American studies.

Conclusion: DM was associated with an increased risk of TB regardless of study design and population. People with DM may be important targets for interventions such as active case finding and treatment of latent TB and efforts to diagnose, detect, and treat DM may have a beneficial impact on TB control.

Figure 1. Flow Chart of Literature Search for Studies on the Association between Diabetes Mellitus and Active Tuberculosis

Figure 2. Forest Plot of the 13 Studies That Quantitatively Assessed the Association between Diabetes and Active Tuberculosis by Study Designs

Size of the square is proportional to the precision of the study-specific effect estimates, and the bars indicate the corresponding 95% CIs. Arrows indicate that the bars are truncated to fit the plot. The diamond is centered on the summary RR of the cohorts studies, and the width indicates the corresponding 95% CI. *Other: The studies by Ponce-de-Leon et al. [7] and Dyck et al. [25] were not specified as prospective cohort or case-control. TB case accrual occurred prospectively, while the underlying distribution of diabetes was determined during a different time period after baseline.

Figure 3. Forest Plot of Age-Specific Association between Diabetes and Active Tuberculosis from Kim et al. [7], Ponce-de-Leon et al. [9], and Dyck et al. [25]

Size of the square is proportional to the precision of the study-specific effect estimates, and the bars indicate 95% CI of the effect estimates. Arrows indicate that the bars are truncated to fit the plot. *Meta-regression: Factor reduction in RR with 10 y increase in age; p-values are given for test of linear trend. HR, hazard ratio.