Impact of Uncontrolled HbA1C on The Outcome of Tuberculosis Treatment in TB Patients With Diabetes

Oki Nugraha Putra, Hardiyono Hardiyono, Fitriyatul Rizkiyah, Affan Yuniar N.H


Pulmonary tuberculosis (TB) is an infection and communicable disease caused by Mycobacterium tuberculosis. One of the risks to develop active tuberculosis is diabetes mellitus (DM), with two or three times higher than TB patients without DM. Several studies have reported that DM was associated with poor clinical outcomes characterized by a delay of smear sputum conversion or culture conversion in TB patients with DM. However, very limited studies that analyze uncontrolled diabetes by HbA1c level with clinical outcome of TB treatment. This study aims to review the correlation between HbA1c levels and sputum or culture conversion in TB patients with DM. Pubmed, Web of Science, and Embase database were used to search and select the article. We included five studies that met the inclusion criteria. Smear conversion rate at two months was lower in TB patients with DM than those without DM. Uncontrolled HbA1c levels > 6.5%-7.0% were significantly associated with smear conversion of culture conversion for more than two months with a high risk of treatment failure. The positive level of smear sputum at 2-3 months or the end of the intensive phase becomes a strong predictor a failure treatment at the end of the advanced phase. It can be concluded that HbA1c levels delay the smear sputum or culture sputum for more than two months. This review highlights a need for more attention to control HbA1c levels in TB patients with DM to achieve a better outcome.



Tuberculosis, Diabetes Mellitus, HbA1c, Smear Conversion, Culture Conversion

Full Text:



[1] Baghei P, Marjani M, Jsvanmard P. Diabetes Mellitus and Tuberculosis Facts and Controversies. J Diabetes Metab Disord. 2013; 20(12):58

[2] World Health Organization: Global Tuberculosis Report. [Online]. 2013 . Available from: global_report/en/.

[3] Baker MA, Harries AD, Jeon CY. The Impact of Diabetes on Tuberculosis Treatment Outcomes: A Systematic Review. BMC Med. 2011; 9:81.

[4] Hemmingsen B, Lund SS, Gluud C. Targeting Intensive Glycaemic Control Versus targeting Conventional Glycaemic Control for Type 2 Diabetes Mellitus. Cochrane Database Syst Rev. 2013;(11) doi: CD008143.

[5] Holman RR, Paul SK, Bethel MA. 10-Year Follow-Up of Intensive Glucose Control in Type 2 Diabetes. N Engl J Med. 2008;359(15):1577–1589

[6] Benfield T, Jensen JS, Nordestgaard BG. Influence of Diabetes And Hyperglycaemia on Infectious Disease Hospitalisation And Outcome. Diabetologia. 2007;50(3):549–554

[7] Davis TM, Weerarathne T, Foong Y. Community Acquired Infections in Type 2 Diabetic Patients and Their Nondiabetic Partners. The Fremantle Diabetes Study. J Diabetes Complications. 2005;19(5):259–263.

[8] Lynge E, Sandegaard JL, ReboljM. The Danish National Patient Register. Scand J PublicHealth. 2011;39(7 suppl):30–33.

[9] Miedema K. Standardization of HbA1c and Optimal Range of Monitoring. Scand J Clin Lab Invest Suppl 2005;240:61‑72.

[10] Leung CC, Lam TH, Chan WM. Diabetic Control And Risk of Tuberculosis: A Cohort Study. Am J Epidemiol 2008;167(12):1486‑1494.

[11] Alisjahbana B, Sahiratmadja E, Nelwan EJ. The effect of Type 2 Diabetes Mellitus on The Presentation and Treatment Response of Pulmonary Tuberculosis. Clin Infect Dis. 2007;45(4):428‑435

[12] Wijayanto A, Burhan E, Nawas A. Pulmonary Tuberculosis in Patients With Diabetes Mellitus Type 2. J Respirol Indones. 2015;35:1‑11.

[13] Rahmawati, Wijaya D, Nazaruddin AM. The Relationship Between Hemoglobin A1c Levels and Sputum Conversion Time in Indonesian Patients with New Cases of Pulmonary Tuberculosis. J Nat Sc Biol Med. 2018:9;217-221

[14] Kulsum ID, Burhan E, Rochismandoko. Faktor yang Mempengaruhi Konversi Sputum BTA Mikroskopik Pada Pasien Tuberkulosis Paru Kasus Baru dengan Diabetes Mellitus. J Resp Ind. 2017; 37(2):109-118

[15] Oceguara-Martinez D, Laborin-Laniando R. Glycemic Control and Rate of Sputum Conversion in Diabetic Patients with Pulmonary Tuberculosis. Lung Dis Treat. 2016; 104. doi:10.4172/2472-1018.1000104

[16] Yoon YS, Jung JW, Jeon EJ. The Effect of Diabetes Control Status on Treatment Response in Pulmonary Tuberculosis: A Prospective Study. Thorax 2017: 72 : 263-270

[17] Chiang CY, Bai KJ, Lin HH. The Influence of Diabetes, Glycemic Control, and Diabetes-Related Comorbidities on Pulmonary Tuberculosis. 2015. Plos One. doi:10.1371/journal.pone.0121698

[18] Jeon CY, Murray MB. Diabetes Mellitus Increases The Risk of Active Tuberculosis: A Systematic Review of 13 Observational Studies. PLoS Med. 2008;5:1091-101.

[19] Bartelink ML, Hoek L, Freriks JP. Infections in Patients With Type 2 Diabetes in General Practice. Diabetes Res Clin Pract. 1998;40(1):15–19.

[20] Thomsen RW, Riis AH, Kjeldsen .Impact of Diabetes and Poor Glycaemic Control on Risk of Bacteraemia With Haemolytic Streptococci Groups A, B, and G. J Infect. 2011; 63(1):8–16.

[21] McKane CK, Marmarelis M, Mendu ML. Diabetes Mellitus and Community-Acquired Bloodstream Infections in The Critically Ill. J Crit Care. 2014;29(1):70–76.

[22] Kornum JB, Thomsen RW, Riis A. Diabetes, Glycemic Control, and Risk of Hospitalization With Pneumonia: A Population-Based Case-Control Study. Diabetes Care. 2008; 31(8):1541–1545.

[23] Leegaard A, Riis A, Kornum JB, et al. Diabetes, Glycemic Control, and Risk of Tuberculosis: A Population-Based Case Control Study. Diabetes Care. 2011;34(12):2530–2535.

[24] Hirji I, Guo Z, Andersson SW. Incidence of Urinary Tract Infection Among Patients With Type 2 Diabetes in The UK General Practice Research Database (GPRD). J Diabetes Complications. 2012;26(6):513–516

[25] Hirji I, Andersson SW, Guo Z Incidence of Genital Infection Among Patients With Type 2 Diabetes in The UK General Practice Research Database. J Diabetes Complications. 2012;26(6):501–505.

[26] Critichley JA, Carey IM, Harris T. Glycemic Control and Risk of Infections Among People With Type 1 or Type 2 Diabetes in Large Primary Care Cohort Study. Diabetes Care. 2018; 41(10):2127-2135

[27] Wahiduddin, Pranoto A, Sudjarwo. Kendali glikemik pada pasien diabetes mellitus tipe 2 dengan dan tanpa tuberculosis paru. Jurnal MKMI. 2019;15(1): 99-109

[28] Boyilla N, Madas S. Relationship between Diabetes Mellitus and Pulmonary Tuberculosis and Outcome of Treatment. International Journal of Advances in Medicine. 2016;(3):504-08.

[29] Ahmed M, Omer I, Osman SM. Association Between Pulmonary Tuberculosis and Type 2 Diabetes in Sudanese Patients. The International Journal of Microbiology. 2017; (6): 97-101

[30] Flyvbjerg A. Diabetic Angiopathy, The Complement System and The Tumor Necrosis Factor Superfamily. Nat Rev Endocrinol. 2010;6(2):94-101.

[31] Casqueiro J, Alves C. Infections in Patients With Diabetes Mellitus: A Review of Pathogenesis. Indian J Endocrinol Metab. 2012 ;16(Suppl1):27-36.

[32] Fidan I, Yüksel S, Kalkanci A. Evaluation of The Natural Killer Cytotoxicity and The Levels of Cytokines in Rats With Type I Diabetes Mellitus. Mem Inst Oswaldo Cruz. 2005;100(8):883- 887.

[33] Berrou J, Fougeray S, Venot M. Natural Killer Cell Function, An Important Target for Infection and Tumor protection, Is Impaired in Type 2 Diabetes. PLoS ONE. 2013;8(4):e62418.

[34] Menart-Houtermans B, Rütter R, Nowotny B. Leukocyte Profiles Differ Between Type 1 and Type 2 Diabetes and Are Associated With Metabolic Phenotypes: Results From the German Diabetes Study (GDS). Diabetes Care. 2014;37(8):2326-2333.

[35] Piatkiewicz P, Czech A, Tatoń J. Glucose Transport in Human Peripheral Blood Lymphocytes Influenced by Type 2 Diabetes Mellitus. Arch Immunol Ther Exp (Warsz). 2007;55(2):119-126.

[36] Ristanti Dian, Soegiarto G, Novida H. Hubungan Antara Kendali Glikemik Pada Pasien Diabetes Mellitus Tipe 2 Dengan Aktivasi Sel Natural Killer. Jurnal Penyakit Dalam Indonesia, 2019: 6(2): 58-63

[37] Jiyani MR, Vadgama PK, Pandey AS. Clinical Profile and Outcome of Tuberculosis in Patients With Diabetes. Int J Res Med. 2015;4:36-40.

[38] Gomez DI, Twahirwa M, Schlesinger LS. Reduced Mycobacterium Tuberculosis Association With Monocytes From Diabetes Patients That Have Poor Glucose Control. Tuberculosis (Edinb). 2013; 93(2): 192–197.

[39] Sugawara I, Mizuno S. Higher Susceptibility of Type 1 Diabetic Rats to Mycobacterium tuberculosis Infection. Tohoku J Exp Med.2008: 216: 363–370.

[40] Buzzo CL, Medina T, Branco LM. Epigenetic Regulation of Nitric Oxide Synthase 2, Inducible (Nos2) by NLRC4 Inflammasomes Involves PARP1 Cleavage. Sci Rep.2017: 7:41686.

[41] Mathews MT, Berk BC. PARP-1 Inhibition Prevents Oxidative and Nitrosative Stress-Induced Endothelial Cell Death Via Transactivation of The VEGF receptor 2. Arterioscler Thromb Vasc Biol.2008; 28:711–717.

[42] Nijland HM, Ruslami R, Stalenhoef JE. Exposure To Rifampicin Is Strongly Reduced in Patients With Tuberculosis and Type 2 Diabetes. Clin Infect Dis. 2006: 43:848–854.

[43] Medellin-Garibay SE, Cortez-Espinosa N, Milan-Segovia RC. Clinical Pharmacokinetics of Rifampin in Patients With Tuberculosis and Type 2 Diabetes Mellitus: Association With Biochemical and Immunological Parameters. Antimicrob Agents Chemother. 2015: 59:7707–7714.

[44] Babalik A, Ulus IH, Bakirci N. Plasma Concentrations of Isoniazid and Rifampin Are Decreased in Adult Pulmonary Tuberculosis Patients With Diabetes Mellitus. Antimicrob Agents Chemother. 2013; 57:5740 –5742.

[45] Ruslami R, Nijland HM, Adhiarta IG. Pharmacokinetics of Antituberculosis Drugs in Pulmonary Tuberculosis Patients With Type 2 Diabetes. Antimicrob Agents Chemother. 2010; 54:1068 –1074.

[46] Hemanth Kumar AK, Kannan T. Pharmacokinetics of Thrice-Weekly Rifampicin, Isoniazid and Pyrazinamide in Adult Tuberculosis Patients in India. Int J Tuberc Lung Dis. 2016: 20:1236 –1241.

[47] Kuswibawati, Pengaruh Pemberian Rifampisin Terhadap Efek Hipoglikemik Glizipid pada Relawan Sehat. Majalah Farmasi Indonesia. 2003; 14(2):299-305.

[48] Siane A, Ascobat P, Instiaty. Comparative Effectiveness of Tuberculosis Treatment Daily Versus Intermitten Regimen in Indonesian TB-DM Patients: Real World Patient Database Study. Acta Med Indones-Indones J Intern Med.2020, 52(1): 25-30

[49] Alfarisi O, Mave V, Gaikwad S. Effect of Diabetes Mellitus on The Pharmacokinetics and Pharmacodynamics of Tuberculosis Treatment. Antimicrobial agents and chemotherapy. 2018; 62(1). doi:

[50] Requena-Mendez A, Davies G, Ardrey A. Pharmacokinetics of Rifampin in Peruvian Tuberculosis Patients With and Without Comorbid Diabetes or HIV. Antimicrob Agents Chemother. 2012; 56:2357–2363.

[51] Wang P, Pradhan K, Zhong XB. Isoniazid Metabolism and Hepatotoxicity. Acta Pharm Sin B. 2016;6(5):384 –392.

[52] Boglou P, Steiropoulos P, Papanas N. Hypoglycaemia Due to Interaction of Glimepiride With Isoniazid in A Patients With Type 2 Diabetes Mellitus. BMJ Case Rep. 2013. doi:10.1136/bcr-2012-008528


Article Metrics

Abstract view : 78 times
PDF - 72 times


  • There are currently no refbacks.

Copyright (c) 2020 Jurnal Profesi Medika : Jurnal Kedokteran dan Kesehatan


Wahidin Sudirohusodo Building, UPN Veteran Jakarta

Jl. RS Fatmawati No 1, Pondok Labu, Jakarta Selatan

Phone: 021-7656904 ; Fax: 021-7692860

Email : WA 085693341215 ; (paper handling / publication issues)

View My Stats Jurnal Profesi Medika