Impact of diabetes mellitus on drug-resistant tuberculosis across resistance categories: a systematic review and meta-analysis

Background: Tuberculosis (TB) and diabetes mellitus (DM) are major global health challenges that frequently coexist. DM has been associated with adverse TB outcomes, but its relationship with specific categories of drug-resistant TB has not been comprehensively synthesised. The association between DM and different drug-resistance categories in patients with TB was quantified, with a primary focus on resistance to first-line anti-TB drugs. Methods: A systematic review and meta-analysis of observational studies was conducted, drawing on evidence identified through seven international and Chinese databases, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Study quality was assessed using the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality checklist. Random-effects models were used to pool odds ratios (ORs) and 95% confidence intervals (CIs). Results: Forty-five studies involving 51 982 participants were included. Compared with patients without DM, those with DM had higher odds of isoniazid-resistant TB (OR = 1.30; 95% CI = 1.14-1.48), rifampicin-resistant TB (OR = 1.37; 95% CI = 1.17-1.59), and multidrug-resistant TB (OR = 1.45; 95% CI = 1.12-1.88). Associations for polydrug-resistant TB and extensively drug-resistant TB were imprecise and were based on relatively few studies. Subgroup analyses suggested possible geographic variation, although the evidence base was heavily concentrated in East Asia. Exploratory analyses of studies reporting glycaemic data suggested that poorer glycaemic control may be associated with higher odds of drug resistance, but definitions and thresholds were inconsistent across studies. Conclusions: DM was associated with higher odds of isoniazid-resistant TB, rifampicin-resistant TB, and multidrug-resistant TB. These findings should be interpreted as associations rather than evidence of causality, but they support closer integration of TB and DM assessment in clinical care and public health practice.