Background: Few studies have investigated the impact of diabetes mellitus (DM), a globally increasing metabolic disease, on treatment outcomes and long-term survival in patients with multidrug-resistant forms of tuberculosis (MDR-TB). Objectives: We analyzed outcomes in a large cohort to assess the impact of DM on treatment outcomes of patients with MDR-TB. Methods: MDR-TB patients newly diagnosed or retreated between 2000 and 2002 and followed for 8-11 years were retrospectively analyzed with respect to the effect of DM as a comorbidity on their treatment outcome and long-term survival. Results: Of 1,407 patients with MDR-TB, 239 (17.0%) had coexisting DM. The mean age and body mass index were higher in MDR-TB patients with DM [MDR-TBDM(+)] than in those without DM [MDR-TBDM(-)]. Patients with MDR-TB and a comorbidity of DM had a significantly lower treatment success rate than those without a history of DM (36.0 vs. 47.2%, p = 0.002). In addition, DM was the negative predictor for MDR-TB treatment success in multivariate analyses [odds ratio 0.51, 95% confidence interval (CI) 0.26-0.99]. Mean survival times were also lower in MDR-TBDM(+) than in MDR-TBDM(-) patients (102 vs. 114 months, p = 0.001), with DM as a significant predictor of poor long-term survival in multivariate analyses (hazard ratio 1.59, 95% CI 1.01-2.50). Conclusions: Among MDR-TB patients, DM was a relatively common comorbidity. In patients undergoing treatment for MDR-TB and followed for 8-11 years, it was found to be independently associated with an increased risk of both treatment failure and death.

Keywords:
Diabetes mellitus, Multidrug-resistant tuberculosis, Treatment, Outcome, Survival
1.
Whiting DR, Guariguata L, Weil C, Shaw J: IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011;94:311-321.
2.
Jeon CY, Murray MB: Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies. PLoS Med 2008;5:e152.
3.
Baker MA, Harries AD, Jeon CY, Hart JE, Kapur A, Lonnroth K, Ottmani SE, Goonesekera SD, Murray MB: The impact of diabetes on tuberculosis treatment outcomes: a systematic review. BMC Med 2011;9:81.
4.
Harries AD, Murray MB, Jeon CY, Ottmani SE, Lonnroth K, Barreto ML, Billo N, Brostrom R, Bygbjerg IC, Fisher-Hoch S, Mori T, Ramaiya K, Roglic G, Strandgaard H, Unwin N, Viswanathan V, Whiting D, Kapur A: Defining the research agenda to reduce the joint burden of disease from diabetes mellitus and tuberculosis. Trop Med Int Health 2010;15:659-663.
5.
Ottmani SE, Murray MB, Jeon CY, Baker MA, Kapur A, Lonnroth K, Harries AD: Consultation meeting on tuberculosis and diabetes mellitus: meeting summary and recommendations. Int J Tuberc Lung Dis 2010;14:1513-1517.
6.
World Health Organization: Collaborative framework for care and control of tuberculosis and diabetes. Geneva, WHO, 2011, Publication No. WHO/HTM/TB/2011.15.
7.
Wright A, Zignol M, Van Deun A, Falzon D, Gerdes SR, Feldman K, Hoffner S, Drobniewski F, Barrera L, van Soolingen D, Boulabhal F, Paramasivan CN, Kam KM, Mitarai S, Nunn P, Raviglione M: Epidemiology of antituberculosis drug resistance 2002-07: an updated analysis of the global project on anti-tuberculosis drug resistance surveillance. Lancet 2009;373:1861-1873.
8.
Orenstein EW, Basu S, Shah NS, Andrews JR, Friedland GH, Moll AP, Gandhi NR, Galvani AP: Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis. Lancet Infect Dis 2009;9:153-161.
9.
Kim HR, Hwang SS, Kim HJ, Lee SM, Yoo CG, Kim YW, Han SK, Shim YS, Yim JJ: Impact of extensive drug resistance on treatment outcomes in non-HIV-infected patients with multidrug-resistant tuberculosis. Clin Infect Dis 2007;45:1290-1295.
10.
Migliori GB, Besozzi G, Girardi E, Kliiman K, Lange C, Toungoussova OS, Ferrara G, Cirillo DM, Gori A, Matteelli A, Spanevello A, Codecasa LR, Raviglione MC: Clinical and operational value of the extensively drug-resistant tuberculosis definition. Eur Respir J 2007;30:623-626.
11.
Kim DH, Kim HJ, Park SK, Kong SJ, Kim YS, Kim TH, Kim EK, Lee KM, Lee SS, Park JS, Koh WJ, Lee CH, Kim JY, Shim TS: Treatment outcomes and long-term survival in patients with extensively drug-resistant tuberculosis. Am J Respir Crit Care Med 2008;178:1075-1082.
12.
Kwon YS, Kim YH, Suh GY, Chung MP, Kim H, Kwon OJ, Choi YS, Kim K, Kim J, Shim YM, Koh WJ: Treatment outcomes for HIV-uninfected patients with multidrug-resistant and extensively drug-resistant tuberculosis. Clin Infect Dis 2008;47:496-502.
13.
Kliiman K, Altraja A: Predictors of poor treatment outcome in multi- and extensively drug-resistant pulmonary TB. Eur Respir J 2009;33:1085-1094.
14.
World Health Organization: Global tuberculosis control 2011. Geneva, WHO, 2011, Publication No. WHO/HTM/TB/2011.16.
15.
Choi YJ, Kim HC, Kim HM, Park SW, Kim J, Kim DJ: Prevalence and management of diabetes in Korean adults: Korea National Health and Nutrition Examination Surveys 1998-2005. Diabetes Care 2009;32:2016-2020.
16.
Park SK, Lee WC, Lee DH, Mitnick CD, Han L, Seung KJ: Self-administered, standardized regimens for multidrug-resistant tuberculosis in South Korea. Int J Tuberc Lung Dis 2004;8:361-368.
17.
World Health Organization: Guidelines for the programmatic management of drug-resistant tuberculosis. Geneva, WHO, 2006, Publication No.WHO/HTM/TB/2006.361.
18.
Alisjahbana B, Sahiratmadja E, Nelwan EJ, Purwa AM, Ahmad Y, Ottenhoff TH, Nelwan RH, Parwati I, van der Meer JW, van Crevel R: The effect of type 2 diabetes mellitus on the presentation and treatment response of pulmonary tuberculosis. Clin Infect Dis 2007;45:428-435.
19.
Dooley KE, Tang T, Golub JE, Dorman SE, Cronin W: Impact of diabetes mellitus on treatment outcomes of patients with active tuberculosis. Am J Trop Med Hyg 2009;80:634-639.
20.
Wang CS, Yang CJ, Chen HC, Chuang SH, Chong IW, Hwang JJ, Huang MS: Impact of type 2 diabetes on manifestations and treatment outcome of pulmonary tuberculosis. Epidemiol Infect 2009;137:203-210.
21.
Moutschen MP, Scheen AJ, Lefebvre PJ: Impaired immune responses in diabetes mellitus: analysis of the factors and mechanisms involved - relevance to the increased susceptibility of diabetic patients to specific infections. Diabete Metab 1992;18:187-201.
22.
Yamashiro S, Kawakami K, Uezu K, Kinjo T, Miyagi K, Nakamura K, Saito A: Lower expression of th1-related cytokines and inducible nitric oxide synthase in mice with streptozotocin-induced diabetes mellitus infected with mycobacterium tuberculosis. Clin Exp Immunol 2005;139:57-64.
23.
Restrepo BI, Fisher-Hoch SP, Pino PA, Salinas A, Rahbar MH, Mora F, Cortes-Penfield N, McCormick JB: Tuberculosis in poorly controlled type 2 diabetes: altered cytokine expression in peripheral white blood cells. Clin Infect Dis 2008;47:634-641.
24.
Singla R, Khan N, Al-Sharif N, Ai-Sayegh MO, Shaikh MA, Osman MM: Influence of diabetes on manifestations and treatment outcome of pulmonary TB patients. Int J Tuberc Lung Dis 2006;10:74-79.
25.
Nijland HM, Ruslami R, Stalenhoef JE, Nelwan EJ, Alisjahbana B, Nelwan RH, van der Ven AJ, Danusantoso H, Aarnoutse RE, van Crevel R: Exposure to rifampicin is strongly reduced in patients with tuberculosis and type 2 diabetes. Clin Infect Dis 2006;43:848-854.
26.
Pamra SP, Prasad G, Mathur GP: Causes of failure of domiciliary chemotherapy in pulmonary tuberculosis. Tubercle 1973;54:185-194.
27.
Fielder JF, Chaulk CP, Dalvi M, Gachuhi R, Comstock GW, Sterling TR: A high tuberculosis case-fatality rate in a setting of effective tuberculosis control: implications for acceptable treatment success rates. Int J Tuberc Lung Dis 2002;6:1114-1117.
28.
Park SW, Shin JW, Kim JY, Park IW, Choi BW, Choi JC, Kim YS: The effect of diabetic control status on the clinical features of pulmonary tuberculosis. Eur J Clin Microbiol Infect Dis 2012;31:1305-1310.
29.
Leung CC, Lam TH, Chan WM, Yew WW, Ho KS, Leung GM, Law WS, Tam CM, Chan CK, Chang KC: Diabetic control and risk of tuberculosis: a cohort study. Am J Epidemiol 2008;167:1486-1494.
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2013
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