Diabetes mellitus and tuberculosis, a systematic review and meta-analysis with sensitivity analysis for studies comparable for confounders

Abstract

Introduction Meta-analyses conducted so far on the association between diabetes mellitus (DM) and the tuberculosis (TB) development risk did not sufficiently take confounders into account in their estimates. The objective of this systematic review was to determine whether DM is associated with an increased risk of developing TB with a sensitivity analyses incorporating a wider range of confounders including age, gender, alcohol consumption, smoke exposure, and other comorbidities. Methods Pubmed, Embase, Web of Science and Global Index Medicus were queried from inception until October 2020. Without any restriction to time of study, geographical location, and DM and TB diagnosis approaches, all observational studies that presented data for associations between DM and TB were included. Studies with no abstract or complete text, duplicates, and studies with wrong designs (review, case report, case series, comment on an article, and editorial) or populations were excluded. The odds ratios (OR) and their 95% confidence intervals were estimated by a random-effect model. Results The electronic and manual searches yielded 12,796 articles of which 47 were used in our study (23 case control, 14 cross-sectional and 10 cohort studies) involving 503,760 cases (DM or TB patients) and 3,596,845 controls. The size of the combined effect of TB risk in the presence of DM was OR = 2.3, 95% CI = [2.0–2.7], I2 = 94.2%. This statistically significant association was maintained in cohort (OR = 2.0, CI 95% = [1.5–2.4], I2 = 94.3%), case control (OR = 2.4, CI 95% = [2.0–2.9], I2 = 93.0%) and cross-sectional studies (OR = 2.5, CI 95% = [1.8–3.5], I2 = 95.2%). The association between DM and TB was also maintained in the sensitivity analysis including only studies with similar proportions of confounders between cases and controls. The substantial heterogeneity observed was mainly explained by the differences between geographic regions. Conclusions DM is associated with an increased risk of developing latent and active TB. To further explore the role of DM in the development of TB, more investigations of the biological mechanisms by which DM increases the risk of TB are needed. Review registration PROSPERO, CRD42021216815.

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

“…Evidence on the association between DM and the risk of LTBI was still limited. Previous meta-analyses had shown that DM was associated with the risk of TB ( 15 , 16 ), yet the association between DM and LTBI was still unclear. Recently, global attention to the association between DM and the risk of LTBI has increased, and there were more observational studies published in recent years, especially for cohort studies ( 17 – 25 ).…”

A scoping review on the risk of tuberculosis in specific population groups: can we expand the World Health Organization recommendations?

“…A meta-analysis published in 2021 with a search up to 2020 [ 26 ] found 49 studies reporting on the risk of TB in adults with diabetes mellitus versus a range of comparator groups. The overall pooled odds ratio estimate of active TB from the 49 studies was 2.33 (95% CI 2.00–2.71), with high between-study heterogeneity (I 2 =94.2%) ( table 1 ).…”

“…A meta-analysis published in 2017 with a search up to 2015 [ 24 ] included many of the same studies captured in the aforementioned 2021 meta-analysis [ 26 ] and presented an overall pooled summary estimate of 2.00 (95% CI 1.78–2.24) combining any measure of association (odds ratio/risk ratio/IRR/hazard ratio (HR)) from 44 studies, with high between-study heterogeneity (I 2 =90.5%). Similar estimates were obtained across subgroup analyses by design and measure of association.…”

“…We identified six meta-analyses: three on the risk of active TB among patients with diabetes mellitus [24][25][26], two on the risk among patients with obstructive lung diseases taking inhaled corticosteroids [27,28] and one on the risk among patients with malignancies [29]. The main features and findings from these meta-analyses are displayed in table 2.…”

Effect of Dysglycemia on Urinary Lipid Mediator Profiles in Persons With Pulmonary Tuberculosis

“…Globally, 15% of active TB cases are estimated to be attributable to DM (5); DM is associated with an increased risk of TB disease (6). We recently reported that DM in persons with TB disease increased the odds of M. tuberculosis (Mtb) transmission to close contacts (7).…”