The study is registered in the PROSPERO database (CRD42022306589) and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [11]. Embase, Cochrane Library, and PubMed were searched on July 31, 2022, without a start date or language restrictions.
Search terms included subject and keywords of DM and LTBI (Supplementary Table 1). To identify additional articles, bibliographic references of related works were searched.
Selection Criteria
The following inclusion criteria were applied: (1) observational studies (cohort, case-control, and cross-sectional); (2) those studies investigating the relationship between diabetes and latent tuberculosis; (3) use of either a tuberculin skin test (TST) and/or an interferon gamma release assay (IGRA) for the diagnosis of LTBI; and (4) reporting of an adjusted effect estimate for the association between diabetes and LTBI.
The following exclusion criteria were applied: (1) study populations including patients with active TB; (2) observational studies providing only crude effect estimates of the association between DM and LTBI; (3) diabetes assessed as an adjusted but not an exposure factor; and (4) abstracts, letters, case reports, or reviews.
Two investigators (GZZ and XG) independently screened article titles and abstracts retrieved from the literature search. Full texts of those potentially eligible studies were further assessed for final inclusion. A third investigator (NC) cross-checked extracted data, with disagreements resolved through a consensus.
Study Selection And Data Extraction
Data extraction was performed using a form that included the following fixed set of fields: title, author, year of publication, country or area, study type, patient demographics, diagnostic method of LTBI, DM definition, and crude and adjusted effect sizes and their 95% CIs. Two investigators (GZZ and XG) independently extracted data from individual studies. Full texts of potentially eligible studies were further assessed for final inclusion. A third investigator (NC) cross-checked extracted data, and disagreements were resolved through a consensus.
Quality Assessment
A modified version of a risk-of-bias tool used in a previous systematic review and the modified Newcastle-Ottawa scale for observational studies were used to assess the quality of included studies [12]. Cohort studies were scored using an 8-point scale to determine overall quality. Studies were classified based on their risk of drift, as follows: low (6–8), moderate (4–5), and high (< 4). Cross–sectional studies were classified based on risk of bias using a 7-point scale, as follows: low (5–7), medium (3–4), and high (< 3). Two investigators (GZZ and XG) independently assessed the methodological quality of the studies, with a third investigator (NC) independently reviewing their assessments. Disagreements were resolved by reaching a consensus.
Data analysis
A random-effects model was used to calculate pooled results with a 95% CI. The I² statistic was used to assess the heterogeneity of included studies, with I² > 50% suggesting significant heterogeneity. The Egger’s test was used to assess the publication bias [13–15]. We also performed subgroup and meta-regression analyses to determine whether study-level factors influenced pooled estimates. Potential factors included differing methods for diagnosing DM, differing methods for diagnosing LTBI, the study population, the background prevalence of LTBI in the study population, and risk of bias.
This meta-analysis was conducted using the “meta” package of R statistical software version 3.4.3 (Schwarzer, 2007; Team, 2017). In addition, to facilitate data collation and analysis, cohort studies showing an association between DM and LTBI using an OR value, had the OR values converted to risk ratio (RR) using a calculation[16].