The effect size of type 2 diabetes mellitus on tuberculosis drug resistance and adverse treatment outcomes

Abstract

2 AbstractObjective: To evaluate the effect size of type 2 diabetes mellitus (T2DM) on tuberculosis (TB) treatment outcomes and multi drug resistance (MDR). Methods:A cohort with 507 individuals with diagnosed TB included 183 with coexistence of T2DM and TB (TB-T2DM). Participants were identified at the time of TB diagnosis and followed during the course of TB treatment. Then we computed relative risks and adjustments by Cox proportional hazards for outcome variables (drug resistance, death, relapse, treatment failure), and the size of their effect as Cohen's-d. Results:Patients with TB-T2DM were more likely to remain positive for acid-fast bacilli after two months of anti-TB treatment RR= [2.01 (95% CI: 1.3, 3.1)], to have drug resistant (DR) [OR 3.5 (1.8, 6.7)] and multi-drug resistant (MDR) TB [OR 3.5 (1.8, 7.1)]. The Cohen's-d for DR or MDR in T2DM was 0.69 when compared with non-DM subjects. The T2DM patients had higher odds of resistance to isoniazid (OR 3.9, 95% CI 2.01, 7.9), rifampicin (OR 3.4, 95%CI: 1.6, 7.2) and pyrazinamide (OR 9.4, 95% CI 2.8, 25.6), and their effect sizes were ≥ 0.67. Patients with TB-T2DM (versus no DM) were more likely to present with MDR TB (HR 3.1; 95% CI 1.7, 5.8; p <0.001), treatment failure (HR 2.04; 95% CI 1.07, 3.8; p 0.02) and relapse (HR 2.1; 95% CI 1.2, 3.8; p 0.002), with effect sizes ≥0.39. Conclusion:T2DM showed a substantial contribution to the presence of DR or MDR-TB and to adverse clinical outcomes during and after TB treatment. Our findings support the importance for routine screening of T2DM among newly-diagnosed TB patients in order to stratify them for immediate DR assessment, and highlight the need for clinical trials to evaluate variations to the standard TB treatment in TB-T2DM to prevent adverse treatment outcomes.Keywords: Tuberculosis, type 2 diabetes mellitus, effect, size 3 IntroductionThe overall prevalence of diabetes mellitus (DM) has increased rapidly as a result of an aging population, urbanization and associated changes lifestyle during the last decades. The International Diabetes Federation (IDF) estimated in 2015 the worldwide prevalence of type 2 diabetes mellitus (T2DM) was 8.8% (415 million people) (IDF). In Mexico, the prevalence of T2DM increased by 4.7% from 1998 to 2012, with a morbidity rate of 358.2 per 100 000 in 2012 (Sistema.Nacional. de.Vigilancia.Epidemiológica, 2013). Meanwhile, the World Health Organization (WHO) reported 9.5 million new cases of TB in 2014 and 1.5 million deaths.( WHO, 2015) In Mexico, the tuberculosis (TB) incidence was 23 per 100,000, reflecting a serious public health problem (Delgado-Sanchez et al., 2015).The increase in prevalence of T2DM has had a significant impact on tuberculosis comorbidity, with prevalence rates ranging from 10% to 30%, mainly affecting developing countries, including Some studies report that T2DM increased two to three times the risk of TB (Dooley & Chaisson, 2009;Jeon & Murray, 2008;Perez-Navarro et al., 2015), and diminishes the success of treatment cure (Baker et al., 2011...

Diabetes and tuberculosis: An important relationship

“…Patients with diabetes–TB co‐infection are more likely to remain positive after initial antitubercular treatment, and to exhibit higher resistance to frontline drugs. Moreover, these people are more likely to have multidrug‐resistant TB, treatment failure, and relapse, as reported in another study from Mexico …”

Diabetes mellitus comorbidity in patients enrolled in tuberculosis drug efficacy trials around the world: A systematic review

“…Since 2010, several large cohort studies reported unfavourable effects of DM on TB outcomes. DM was associated with more severe clinical manifestations of TB such as higher frequency of cavities on chest X‐ray and higher hospitalization rates . Patients with DM were more likely to have up to 2 times higher TB reactivation, recurrence, and relapse .…”

“…DM was associated with more severe clinical manifestations of TB such as higher frequency of cavities on chest X‐ray and higher hospitalization rates . Patients with DM were more likely to have up to 2 times higher TB reactivation, recurrence, and relapse . TB‐DM patients were more likely to have delayed sputum conversion and higher probability of treatment failure .…”

“…Patients with DM were more likely to have up to 2 times higher TB reactivation, recurrence, and relapse . TB‐DM patients were more likely to have delayed sputum conversion and higher probability of treatment failure . A recent systematic review showed that glycaemic control has a favourable effect on TB treatment outcomes and, conversely, uncontrolled DM or poor glycaemic control (i.e.…”

Diabetes mellitus and tuberculosis—a double whammy

“…Diabetes predisposes to tuberculosis due to the profound effects of hyperglycemia on body defense mechanisms including suppression of cell-mediated immune mechanisms [10]. It is also well known that presence of diabetes mellitus also alters the way pulmonary tuberculosis manifests and adversely affects clinical and treatment outcomes [11]. It also results in slow conversion to a sputum-negative state [12].…”