The Effect of Diabetes and Prediabetes on Antituberculosis Treatment Outcomes: A Multicenter Prospective Cohort Study

Abstract

Background: It is unclear whether diabetes or prediabetes affects unfavorable treatment outcomes and death in people with tuberculosis (PWTB).

Methods: Culture-confirmed, drug-susceptible PWTB, enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between 2015 and 2019 (N = 643) were stratified based on glycemic status according to baseline glycated hemoglobin. Unfavorable tuberculosis (TB) outcome was defined as treatment failure or modification, recurrence, or death; favorable outcome was cure or treatment completion. We corroborated the findings using data from PWTB reported to the Brazilian National System of Diseases Notification (SINAN) during 2015-2019 (N = 20 989). Logistic regression models evaluated associations between glycemic status and outcomes.

Results: In both cohorts, in univariate analysis, unfavorable outcomes were more frequently associated with smoking, illicit drug use, and human immunodeficiency virus infection. Diabetes, but not prediabetes, was associated with unfavorable outcomes in the RePORT-Brazil (adjusted relative risk [aRR], 2.45; P < .001) and SINAN (aRR, 1.76; P < .001) cohorts. Furthermore, diabetes was associated with high risk of death (during TB treatment) in both RePORT-Brazil (aRR, 2.16; P = .040) and SINAN (aRR, 1.93; P = .001).

Conclusions: Diabetes was associated with an increased risk of unfavorable outcomes and mortality in Brazilian PWTB. Interventions to improve TB treatment outcomes in persons with diabetes are needed.

Keywords: Mycobacterium tuberculosis; SINAN; diabetes; prediabetes; treatment outcome.

Figure 1.

Study flowchart presenting the people with tuberculosis (TB) included and excluded from Regional Prospective Observational Research in Tuberculosis (RePORT)–Brazil (A) and reported to the Brazilian National System of Diseases Notification (SINAN, B) between 2015 and 2019.

Figure 2.

Distribution of glycemic status and glycated hemoglobin (HbA1c) levels according to treatment outcomes in patients with tuberculosis (TB) in the Regional Prospective Observational Research in Tuberculosis–Brazil cohort. Frequency of TB patients with diabetes, prediabetes, normoglycemia, and dysglycemia (diabetes + prediabetes) diagnosed using HbA1c levels is shown according to TB treatment outcome (cure, treatment modification, failure, death, and recurrence). Only comparisons (frequency dysglycemia status between TB treatment outcomes) with significant P values are displayed. Scatterplots depict the frequency of HbA1c values in TB patients according to TB treatment outcome. Lines represent median and interquartile range. The differences in median values of HbA1c between groups were compared using the Kruskal–Wallis test with Dunn multiple comparisons posttest. Only comparisons with significant P values are displayed. Abbreviations: HbA1c, glycated hemoglobin, normoglyc., normoglycemia.

Figure 3.

Association between glycemic status and tuberculosis (TB) treatment outcomes among TB patients from the Regional Prospective Observational Research in Tuberculosis (RePORT)–Brazil and the Brazilian National System of Diseases Notification (SINAN) cohorts. In the RePORT cohort (upper panel), logistic regression was performed to evaluate the independent associations between glycemic status of TB patients (model 1: dysglycemia; model 2: diabetes; model 3: prediabetes; model 4: increases of 1 unit in glycated hemoglobin level) and variables with P value < .2 in the univariate analyses (Table 1) and unfavorable treatment outcome (treatment modification, failure, recurrence, and death). Comparisons of diabetes, prediabetes, and dysglycemia were performed using normoglycemia as the reference. In the SINAN cohort (lower panel), logistic regression was performed to evaluate the independent associations between diabetes and unfavorable TB treatment outcome (treatment modification, treatment failure, and death). Variables with P < .2 in the univariate analyses (Table 2) were included. Details of the bivariate binomial logistic regression models are shown in Supplementary Table 2. Abbreviations: CI, confidence interval; HbA1c, glycated hemoglobin; RePORT, Regional Prospective Observational Research for Tuberculosis; SINAN, National System of Diseases Notification; TB, tuberculosis.

Figure 4.

Association between glycemic status and death during antituberculosis treatment among tuberculosis (TB) patients from the Regional Prospective Observational Research for Tuberculosis (RePORT)–Brazil and the Brazilian National System of Diseases Notification (SINAN) cohorts. In the RePORT cohort (upper panel), logistic regression was performed to evaluate the independent associations between glycemic status of TB patients (model 1: dysglycemia; model 2: diabetes; model 3: prediabetes; model 4: increases of 1 unit in glycated hemoglobin level) and variables with P < .2 in the univariate analyses (Supplementary Table 3) and death. Comparisons of diabetes, prediabetes, and dysglycemia were performed using normoglycemia as reference. In the SINAN cohort (lower panel), logistic regression was performed to evaluate the independent associations between diabetes in TB patients in the period 2015–2019 and variables with P < .2 in the univariate analyses (Supplementary Table 4) and death. Details of the bivariate binomial logistic regression models are shown in Supplementary Table 5. Abbreviations: CI, confidence interval; HbA1c, glycated hemoglobin; RePORT, Regional Prospective Observational Research for Tuberculosis; SINAN, National System of Diseases Notification; TB, tuberculosis.