Influence of Diabetes Mellitus on the Development of Multidrug-Resistant Tuberculosis (MDR-TB) in Relation With Genetic Mutations of M. tuberculosis Isolates in Ethiopia.

Abstract

In nations with developing healthcare infrastructures, the dual burden of Type 2 diabetes mellitus (T2DM) and tuberculosis represents a critical health challenge. The aim of this study is to investigate the influence of T2DM on the development of multidrug-resistance tuberculosis (MDR-TB) in relation to genetic mutations of Mycobacterium tuberculosis in Ethiopia. A facility-based cross-sectional study was carried out between 2023 and 2024. Genetic mutations associated with drug resistance in both diabetic and nondiabetic groups were detected using line probe assays (LPAs). Diagnosis of T2DM was performed using fasting blood glucose and glycated hemoglobin levels. Data were analyzed with SPSS software, and logistic regression models were performed. Our findings revealed that 44 of the 182 participants (24.2%) were TB-T2DM, whereas 138 (75.8%) were TB with nondiabetic groups. Multivariate analysis displayed that the prior TB treatment history (aOR: 2.51, 95%CI: 1.02-6.19, p = 0.046) and a family history of T2DM (aOR: 2.25, 95% CI: 1.10-4.60, p = 0.031) were independently associated with an increased risk of TB-T2DM comorbidity. Genetic analysis identified a total of 50 mutations (22 rpoB, 22 katG, and 6 inhA promoter) associated with resistance to RIF and INH drugs among 31 drug-resistant M. tuberculosis isolates, which were significantly more common in TB-T2DM comorbid patients (p = 0.009). The rpoB S450L and katG S315T1 were the predominant mutations typically associated with high-level RIF and INH resistance, respectively, and high biological fitness, allowing for successful transmission within the community. Among the dual mutations identified in MDR-TB isolates, only the rpoB UN + katG S315T1 mutation was significantly more prevalent in nondiabetics (p = 0.04) compared to the TB-T2DM comorbid group. Multivariate analysis revealed that prior TB treatment history (aOR: 4.00, 95% CI: 1.31-12.50, p = 0.014) and TB-T2DM comorbidity (aOR: 3.12, 95% CI: 1.02-9.10, p = 0.042) were significantly associated with an increased likelihood of MDR-TB. This increased odd of resistance in comorbid patients highlights the need for bidirectional T2DM screening for all TB patients, particularly those with a history of prior TB treatment or a family history of diabetes. A genome-wide association study into the mutation patterns responsible for DR is crucial to inform the development of targeted, effective strategies moving forward.