α-Glucosidase Inhibitor Can Effectively Inhibit the Risk of Tuberculosis in Patients with Diabetes: A Nested Case-Control Study

Abstract

Diabetes mellitus (DM) and tuberculosis (TB) are major public health and economic burdens. DM increases Mycobacterium tuberculosis (M.tb) infection rates and treatment durations. This study evaluated the relationship between five classes of oral DM medications and TB infection risk in DM patients. We used longitudinal records from the Taiwan Longitudinal Health Insurance Research Database. DM patients were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 250 and A code A181. TB patients were identified using ICD-9-CM code 010.x-017.x. Oral DM medications were divided into five classes: sulfonylureas, biguanides, meglitinides, α-glucosidase inhibitors (AGIs), and thiazolidinediones. Users were classified as nonusers, low-concentration users, and high-concentration users. The incidence rate ratio (IRR) was derived using multivariate Poisson regression to calculate the relative risk of TB infection. DM patients using low- and high-concentration AGIs had significantly lower TB infection risks compared with nonusers. The IRRs of the sulfonylureas and AGI users were [CI] 0.693–0.948) and (95% CI 0.651–0.995), respectively. The other four classes of medications exhibited no significant effect on TB infection risk in DM patients. Furthermore, DM patients using high-concentration AGIs had a significantly lower TB infection risk compared with those using low-concentration AGIs (IRR 0.918, 95% CI: 0.854–0.987). We noted a dose-response relationship in the effects of DM medications on TB risk. Accordingly, we suggest that DM patients use AGIs to benefit from their protective effect on TB infection risk.

Mitigating Candidiasis with Acarbose by targeting Candida albicans α-Glucosidase: In- silico, In-vitro and Transcriptomic Approaches

“…Hence, we report for the rst time, the off-target use of acarbose as an anti-bio lm compound against C. albicans. Previous reports on Acarbose showed biphasic behavior for Mycobacterium smegmatis where bio lm stimulation at lower concentrations (100 µg/mL) and bio lm inhibition at higher concentrations of 500 µg/mL were observed 25 . In our study, the reverse was observed where the bio lm inhibition was observed at an extremely low concentration of ~ 90 nM without affecting the fungal growth.…”

Mitigating candidiasis with acarbose by targeting Candida albicans α-glucosidase: in-silico, in-vitro and transcriptomic approaches

“…Hence, we report for the first time, the off-target use of acarbose as an anti-biofilm compound against C. albicans. Previous reports on Acarbose showed biphasic behavior for Mycobacterium smegmatis where biofilm stimulation at lower concentrations (100 µg/mL) and biofilm inhibition at higher concentrations of 500 µg/mL were observed 25 . In our study, the reverse was observed where the biofilm inhibition was observed at an extremely low concentration of ~ 90 nM without affecting the fungal growth.…”

Protein targets in Mycobacterium tuberculosis and their inhibitors for therapeutic implications: A narrative review

“…The first-line anti-TB drugs isoniazid and ethionamide have to be activated by KatG or EthA, respectively, further to generate reactive oxygen species (ROS) [30]. It is been reported elsewhere, thiadiazolyl methyl thiazoles, a novel tetracyclic thiadiazole-based compound, as an inhibitor of InhA, which was further validated based on its mechanism of action and revealed its binding mode in the active site [8]. Isoniazidresistant strains (promoter mutation at inhA) can be targeted using tetrahydro pyranyl methyl benzamides [29].…”

“…The NamH imparts unique structural modifications to Mtb PG, which provides the ability to withstand lysozymatic degradation of the PG layer [4]. The Mur C -F pathway proteins (ATP-dependent ligases) are coded by single-copy genes and are unique to prokaryotes and are attractive therapeutic targets to prevent the growth of microorganisms [8]. The MurI, a glutamate racemase, provides the substrate (D-Glu) necessary for PG synthesis.…”