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The effect of diabetes mellitus on mortality during rifampicin-resistant tuberculosis treatment in Indonesia: a retrospective cohort study

L D Veeken(1) A D Salindri(2) P Santoso(3) A V Miranda(4) W Sukmawati(4) B W Lestari(4) N N M Soetedjo(3,4) A Y Soeroto(3) R Van Crevel(1,5)

1:Radboud University Medical Center; 2:Stanford University School of Medicine; 3:Hasan Sadikin Hospital; 4:Universitas Padjadjaran; 5:University of Oxford

Diabetes increases the risk of tuberculosis (TB) disease, TB deaths and drug-resistant TB. We determined the effect of diabetes on all-cause mortality during rifampicin-resistant TB treatment in Indonesia, which has the second-highest TB burden globally and a rapidly growing diabetes prevalence. The cohort included individuals aged ≥18 years old with Xpert MTB/RIF-confirmed rifampicin-resistant TB treated in a tertiary referral hospital between March 2020 and May 2022. We collected routinely measured hospital data and used baseline HbA1c levels to categorize individuals as diabetes (HbA1c≥6.5%), pre-diabetes (HbA1c≥5.7% and <6.5%), and no diabetes (HbA1c<5.7%). Cox proportional hazards regression was used to analyse the association between diabetes and all-cause mortality. In total, 345 individuals with rifampicin-resistant TB were included (median age 38 (IQR: 28-50), 57% male, 1.7% HIV).  Of 276 with further resistance testing, 56% had MDR-TB and 9.1% pre-XDR. Sixty-two died during treatment (18%; 95% CI: 14-22) and diabetes was diagnosed in 96 (28%; 95% CI: 23-33), half of whom had newly diagnosed diabetes. The adjusted hazard rates of all-cause mortality during rifampicin-resistant TB treatment were higher among people living with diabetes (PLWD) compared to those without diabetes (aHR = 1.86 (95% CI: 0.97-3.57)), and especially among underweight PLWD (aHR = 2.63 (95% CI: 1.15 – 6.00)). Moreover, treatment failure was substantial (13%) but not higher among PLWD. In conclusion, diabetes in rifampicin-resistant TB is common and associated with increased all-cause mortality during second-line treatment in Indonesia. More effort is needed to understand this effect, and improve treatment outcomes of diabetes-associated drug-resistant TB.

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