Diabetes Mellitus and Tuberculosis Treatment Outcomes in Pune, India

Abstract

Background Diabetes mellitus (DM) increases the risk of tuberculosis (TB) disease. Knowledge of the impact of DM on TB treatment outcomes is primarily based on retrospective studies. Methods We conducted a prospective cohort study of new pulmonary TB patients with and without DM (TB-DM and TB-only) in India. The association of DM with a composite unfavorable TB treatment outcome (failure, recurrence, mortality) over 18 months was determined and the effect of DM on all-cause mortality and early mortality (death during TB treatment) was assessed. Results Of 799 participants, 574(72%) had TB-only and 225(28%) had TB-DM. The proportion of patients with DM who experienced the composite outcome was 20% as compared to 21% for TB only participants (adjusted hazard ratio 1.13, 95% CI 0.75–1.70). Mortality was higher in participants with DM (10% vs. 7%), and early mortality was substantially higher among patients with DM (adjusted hazard ratio [aHR] 4.36; 95% CI:1·62–11.76). Conclusion DM was associated with early mortality in this prospective cohort study, but overall unfavorable outcomes were similar to participants without DM. Interventions to reduce mortality during TB treatment among people with TB-DM are needed.

Diabetes-Associated Susceptibility to Tuberculosis: Contribution of Hyperglycemia vs. Dyslipidemia

“…Several retrospective studies have demonstrated adverse TB treatment outcomes and higher mortality in TB patients with T2D [19,30]. A recent prospective study following more than 700 individuals from West India showed that T2D significantly increased the risk of early mortality during TB treatment (aHR, 4.36; 95% CI, 1.62-11.76) [31]. A multi-center prospective cohort study from Brazil demonstrated that participants with diabetes but not prediabetes are at higher risk of having an unfavourable outcome (1.76 and 2.45 times separately from two different cohorts) and an increased risk of death (1.93 and 2.16 times) [32].…”

“…Although T2D in Western populations is often associated with obesity, a significant proportion of T2D cases, particularly in Asian populations, do not have a high BMI [34]. A prospective cohort study of 225 new pulmonary TB patients with comorbid T2D in India found that low and normal BMI were more common among TB patients with T2D than high BMI (88% vs. 12%) [31]. Similar proportions between T2D with and without low BMI was also reported by Kubiak et al in a cross-sectional analysis of active TB cases in southern India (90.3% vs. 9.7%) [35].…”

Diabetes-associated Susceptibility to Tuberculosis: Contribution of Hyperglycemia vs. Dyslipidemia

“…Several retrospective studies have demonstrated adverse TB treatment outcomes and higher mortality in TB patients with T2D [19,30]. A recent prospective study following more than 700 individuals from West India showed that T2D significantly increased the risk of early mortality during TB treatment (aHR, 4.36; 95% CI, 1.62-11.76) [31]. A different study also conducted in India surprisingly found that poorly controlled T2D was not associated with higher odds of adverse TB treatment outcomes among TB patients with normal or high BMI and was associated with better TB outcomes among patients with low BMI [32].…”

“…While T2D in Western populations is often associated with obesity, a significant proportion of T2D cases, particularly in Asian populations, do not have a high BMI [33]. A prospective cohort study of 225 new pulmonary TB patients with comorbid T2D in India found that low and normal BMI were more common among TB patients with T2D than high BMI (88% vs. 12%) [31]. Similar proportion between T2D with and without low BMI was also reported by Kubiak et al in a cross-sectional analyses of active TB cases in southern India (90.3% vs. 9.7%) [34].…”

“…A recent large study involving over 75,000 T2D patients confirmed the protective effect of metformin, however only at the highest cumulative dose, whereas lower metformin doses did not reduce the incidence of active TB within a timeframe of two years [77]. In TB patients, metformin use was associated with significantly improved sputum culture conversion rates, fewer pulmonary cavities and reduced mortality rates [31,78,79]. Importantly, these positive effects have been shown to be independent of the degree of blood glucose control [79] suggesting other possible underlying mechanisms mediated by metformin besides direct effects on blood glucose control could underpin the improvement of TB outcomes.…”