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

Abstract

Background It is unclear whether diabetes or prediabetes affect unfavorable treatment outcomes and death in people with tuberculosis (PWTB). Methods Culture-confirmed drug-susceptible PWTB, enrolled in Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil between 2015-2019 (n=643) were stratified based on glycemic status according to baseline glycated hemoglobin. Unfavorable 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 HIV infection. Diabetes, but not prediabetes, was associated with unfavorable outcomes in the RePORT-Brazil (adjusted Relative Risk [aRR]: 2.45, p<0.001) and SINAN (aRR: 1.76, p<0.001) cohorts. Furthermore, diabetes was associated with high risk of death (during TB treatment) in both RePORT-Brazil (aRR:2.16, p=0.040) and SINAN (aRR:1.93, p= 0.001). Conclusion Diabetes was associated with an increased risk of unfavorable outcomes and mortality in Brazilian PWTB. Interventions to improve tuberculosis treatment outcomes in persons with diabetes are needed.

Clinical, laboratory, and radiographic aspects of patients with pulmonary tuberculosis and dysglycemia and tuberculosis treatment outcomes

“…Em países com alta carga de tuberculose, como o Brasil, há poucos estudos prospectivos nos quais se analisam as características clínicas, microbiológicas e radiográficas de pacientes com TBP ou o papel do DM e pré-DM nos desfechos do tratamento da TBP. (8,10) Em nosso estudo, a frequência de DM em pacientes com TBP (14,2%) foi maior do que a relatada em outro estudo realizado no Brasil (8) e mais próxima das relatadas em outras séries (de 12,8% a 25%), (16)(17)(18)(19) porém menor do que a relatada em um estudo realizado na Índia, (15) no qual a proporção de pacientes com tuberculose e DM foi de 30%. Em países como a China (20) e o Quênia, (21) a frequência de DMTB é menor (5,0% e 6,3%, respectivamente) do que a observada em nosso estudo.…”

“…Em nosso estudo, o pré-DM foi identificado em 47,1% dos pacientes com tuberculose, valor superior ao descrito em outros estudos, com prevalência de 7,4% a 37,5%. (8,16,17,(19)(20)(21) No entanto, observamos uma redução significativa dos níveis de HbA1c no segundo mês de tratamento. A normalização dos níveis glicêmicos durante o tratamento da tuberculose em pacientes inicialmente disglicêmicos também foi relatada por outros autores.…”

“…(6) Em países nos quais a carga de tuberculose é alta, ainda há poucos estudos prospectivos avaliando o papel da disglicemia (DM e pré-DM) na apresentação clínica da tuberculose e na resposta ao tratamento da doença em condições de rotina. (7,8) Dados sobre DMTB fornecidos pelo Ministério da Saúde do Brasil (9) e baseados em casos de tuberculose notificados ao Sistema de Informação de Agravos de Notificação mostram que, entre 2019 e 2021, 10% dos pacientes com tuberculose relataram que eram diabéticos.…”

Immunologic, metabolic and genetic impact of diabetes on tuberculosis susceptibility

“…T2DM is significantly associated with adverse TB treatment outcomes and mortality ( 42 , 44 ). In addition, T2DM is associated with early mortality during TB treatment (adjusted hazard ratio: 4.36; 95% confidence interval: 1.62–11.76) ( 48 ), and more than a 2- fold increased risk of death (2.16 times) ( 49 ).…”

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

“…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].…”