Tuberculosis-diabetes Co-morbidity Research Articles

Effect of Lifestyle Modification Intervention on Diabetes Mellitus Treatment Outcomes in Tuberculosis Patients with Diabetes Mellitus in Southwest Nigeria

There is an observed poor treatment outcome of Diabetes mellitus (DM) in patients with Tuberculosis and Diabetes (TBDM) comorbidity due to interference of drugs used in the treatment of Tuberculosis (TB) with first- line drugs used in the treatment of DM. Insulin does not interact with TB drugs, but it is not accessible and affordable to low–resource communities due to high cost. Hence a lifestyle-based intervention, which this study evaluated to determine its effect on Diabetes control in these individuals. It is a quasi-experimental intervention with two groups of 25 participants each as experimental and control cohorts, enrolled from Tuberculosis Healthcare centers in Lagos and Oyo states. The questionnaires were administered after the baseline Glycated hemoglobin (HBA1c) has been measured, repeated after 12 weeks, and analyzed with SPSS software. In the control cohort, the difference in the means of HBA1c was statistically significant at 95%CI: 1.1(0.2 – 2.1; p<0.05), indicating a worsening of blood glucose control. The difference in the means of educational scores was not significant 95%CI: -0.04(-2.8 – 2.7; p<0.05), showing no uptake. In the intervention group, the difference in the means of the HBA1c was statistically significant 95%CI: -2.4(-3.1 – 1.6: p<0.05), indicating improvement in glucose control. The difference in the means of the educational and behavioral score was significant statistically 95%CI: 40.6(37.7 – 43.6; p<0.05) indicating uptake of behavioral changes. The intervention with educational and behavioral lifestyle modifications improved the blood glucose control as an adjunct to the conventional treatment with drugs compared to the control group. Keywords: Behavioral change, Lifestyle, Treatment, Tuberculosis-Diabetes comorbidity.

Metformin promotes smear conversion in tuberculosis-diabetes comorbidity and construction of prediction models.

The comorbidity of tuberculosis (TB) and diabetes mellitus (DM) is a global health concern. Metformin is commonly used in DM but the potential effectiveness in comorbid patients is uncertain. This retrospective study aims to investigate the effect of metformin on TB-DM comorbidity and construct prediction models. Patients diagnosed with TB-DM in West China Hospital were retrospectively enrolled from Nov 2013 to Sep 2019. Electronic health records of patients were extracted. Two-month smear conversion (2SC) was considered an outcome indicator of TB. Univariate and multivariate logistic regression (LR) were used to assess the role of metformin and other independent predictors. Meanwhile, prediction models were built by LR, elastic net regression, support vector machine, k-nearest neighbors, and random forest. A total of 927 individuals were recruited, among which 408 (44.01%) were metformin-exposed patients. A higher 2SC rate was observed in the metformin users. Other impact factors such as smoking, glucose, and creatinine levels were also identified. Multivariable models were then constructed using filtered variables. The support vector machine model yields the highest AUC (0.808, 95% CI: 0.767-0.849) and specificity (83.24%). LR model outperformed others in terms of sensitivity (69.71%). This retrospective study of a large population from southwestern China provides strong clinical evidence for the positive effects of metformin in TB-DM. Metformin is associated with a better therapeutic outcome and promising for the adjuvant therapy of TB-DM. Furthermore, a combination of support vector machine and LR models is recommended to discriminate the patients with poor treatment outcomes.

Vulnerable territories to tuberculosis-diabetes mellitus comorbidity in a northeastern Brazilian scenario.

Epidemiological investigations on tuberculosis-diabetes comorbidity using spatial analysis should be encouraged towards a more comprehensive view of the health of individuals affected by such comorbidity in different contexts. This study analyzes the territories vulnerable to tuberculosis-diabetes comorbidity in a municipality in northeastern Brazil using spatial analysis techniques. An ecological study was carried out in Imperatriz, Maranhão, Brazil. Tuberculosis-diabetes cases reported in the Brazilian Notifiable Diseases Information System between 2009 and 2018 were analyzed. Kernel density estimation and spatial scanning techniques were used to identify the areas with the greatest occurrence of spatial clusters. A heterogeneous spatial distribution was found, ranging from 0.00 to 4.12 cases/km2. The spatial scanning analysis revealed three high-risk spatial clusters with statistical significance (p < 0.05), involving eleven strictly urban sectors with a relative risk of 4.00 (95% CI: 2.60-6.80), 5.10 (95% CI: 2.75-7.30), and 6.10 (95% CI: 3.21-8.92), indicating that the population living in these areas had a high risk of tuberculosis-diabetes comorbidity. The highest concentration of cases/km2, as well as risk clusters, were found in areas with high circulation of people and socio-economic and environmental vulnerabilities. Such findings reinforce the need for public health interventions to reduce social inequalities.

Effect of anti-tuberculosis treatment on the systemic levels of tissue inhibitors of metalloproteinases in tuberculosis – Diabetes co-morbidity

ObjectivesTo study the association of Tissue inhibitors of matrix metalloproteinases (TIMP) levels with tuberculosis-diabetes comorbidity (TB-DM) comorbidity at baseline and in response to anti-TB treatment (ATT). MethodsWe examined the levels of TIMP-1, -2, -3 and -4 in pulmonary tuberculosis alone (TB) or TB-DM at baseline and after ATT. ResultsTIMP-1, -3 and -4 were significantly increased in TB-DM compared to TB at baseline and after ATT. ATT resulted in a significant reduction in TIMP-2 and -3 levels and a significant increase in TIMP-1 in both TB and TB-DM. TIMP-1, -3 and -4 were also significantly increased in TB-DM individuals with bilateral, cavitary disease and also exhibited a positive relationship with bacterial burden in TB-DM and HbA1c in all TB individuals. Within the TB-DM group, those known to be diabetic before incident TB (KDM) exhibited higher levels of TIMP-1, -2, -3 and -4 at baseline and TIMP-2 at post-treatment compared to those newly diagnosed with DM (NDM). KDM individuals on metformin treatment exhibited lower levels of TIMP-1, -2 and -4 at baseline and of TIMP-4 at post-treatment. ConclusionsTIMP levels were elevated in TB-DM, associated with disease severity and bacterial burden, correlated with HbA1c levels and modulated by duration of DM and metformin treatment.

Systemic RAGE ligands are upregulated in tuberculosis individuals with diabetes co-morbidity and modulated by anti-tuberculosis treatment and metformin therapy

BackgroundLigands of the receptor for advanced glycation end products (RAGE) are key signalling molecules in the innate immune system but their role in tuberculosis-diabetes comorbidity (TB-DM) has not been investigated.MethodsWe examined the systemic levels of soluble RAGE (sRAGE), advanced glycation end products (AGE), S100A12 and high mobility group box 1 (HMGB1) in participants with either TB-DM, TB, DM or healthy controls (HC).ResultsSystemic levels of AGE, sRAGE and S100A12 were significantly elevated in TB-DM and DM in comparison to TB and HC. During follow up, AGE, sRAGE and S100A12 remained significantly elevated in TB-DM compared to TB at 2nd month and 6th month of anti-TB treatment (ATT). RAGE ligands were increased in TB-DM individuals with bilateral and cavitary disease. sRAGE and S100A12 correlated with glycated hemoglobin levels. Within the TB-DM group, those with known diabetes (KDM) revealed significantly increased levels of AGE and sRAGE compared to newly diagnosed DM (NDM). KDM participants on metformin treatment exhibited significantly diminished levels of AGE and sRAGE in comparison to those on non-metformin regimens.ConclusionsOur data demonstrate that RAGE ligand levels reflect disease severity and extent in TB-DM, distinguish KDM from NDM and are modulated by metformin therapy.

Plasma Eicosanoid Levels in Tuberculosis and Tuberculosis-Diabetes Co-morbidity Are Associated With Lung Pathology and Bacterial Burden.

Host eicosanoids are lipid mediators of inflammation that are commonly accepted as important modulators of the host immune response in Mycobacterium tuberculosis infection. During active tuberculosis (TB), eicosanoids may play an important role in the regulation of inflammatory responses. However, a detailed investigation of the relationship of eicosanoids in TB and TB-diabetes comorbidity (TB-DM) and association to disease pathology or bacterial burdens has not been studied. To study this, we examined the plasma levels of Lipoxin A4 (LXA4), 15-epi-LXA4, Leukotriene B4 (LTB4), and Prostaglandin E2 (PGE2) in individuals with either TB-DM, TB, diabetes mellitus (DM) or healthy controls (HC). Plasma levels of LXA4, 15-epi-LXA4, and PGE2 were significantly increased while the levels of LTB4 were significantly decreased in TB-DM and TB group compared to DM and HC. The ratio of LXA4 to LTB4 and 15-epiLXA4 to LTB4 was significantly enhanced in TB-DM compared to TB. Moreover, the levels of LXA4, 15-epi-LXA4 and the ratios of LXA4 to LTB4 and 15-epiLX4 to LTB4 were significantly increased in TB individuals with bilateral or cavitary disease and these markers also revealed a significant positive relationship with bacterial burden. At the completion of anti-tuberculosis therapy (ATT), levels of LXA4, 15-epi-LXA4, and PGE2 in TB-DM and TB groups were diminished and levels of LTB4 were enhanced in the TB group compared to pre-treatment. Our data imply that alteration and upregulation of eicosanoids are standard characteristics of TB-DM co-morbidity. Our data also demonstrate that modulation in the eicosanoid levels reflect disease severity and extent in TB and TB-DM and are modulated by ATT.

Elevated circulating levels of monocyte activation markers among tuberculosis patients with diabetes co-morbidity.

Alteration in the frequency of monocyte subsets is a hallmark of tuberculosis-diabetes co-morbidity (TB-DM). To study this association, we examined the plasma levels of sCD14, sCD163, C-reactive protein (CRP) and soluble tissue factor (sTF) in individuals with TB-DM, TB or diabetes mellitus (DM), and in healthy controls (HC). Circulating levels of sCD14, sCD163 and sTF were significantly increased in TB-DM and DM compared with TB and HC; however, CRP was significantly increased in TB-DM and TB compared with DM and HC. During longitudinal follow up, sCD14, CRP and sTF levels remained significantly increased in TB-DM compared with TB from baseline (pre-treatment), during treatment (2nd month) and at the completion (6th month) of anti-TB treatment (ATT), whereas sCD163 was significantly higher in TB-DM compared with TB only at baseline. Moreover, the levels of sCD14 and sCD163 were significantly higher in TB-DM individuals with bilateral and cavitary disease and exhibited a significant positive relationship with bacterial burden. Levels of sCD14, sCD163 and CRP exhibited a positive relationship with HbA1c levels. Within the TB-DM group, those with known diabetes before incident TB (KDM) exhibited significantly higher levels of sCD14 and sCD163 compared with individuals with newly diagnosed DM with TB (NDM). Finally, KDM individuals on metformin treatment exhibited significantly lower levels of sCD14, sCD163 and CRP compared with those on non-metformin-containing regimens. Our data demonstrate that systemic monocyte activation marker levels reflect baseline disease severity and extent in TB-DM, differentiate KDM from NDM and are modulated by ATT and metformin therapy.

Elevated levels of matrix metalloproteinases reflect severity and extent of disease in tuberculosis-diabetes co-morbidity and are predominantly reversed following standard anti-tuberculosis or metformin treatment

BackgroundMatrix metalloproteinases (MMPs) are considered to be key mediators of tuberculosis (TB) pathology but their role in tuberculosis – diabetes comorbidity (TB-DM) is not well understood.MethodsTo study the association of MMP levels with severity and extent of disease as well as bacterial burden in TB-DM, we examined the systemic levels of MMP-1, − 2, − 3, − 7, − 8, − 9, − 10, − 12 and − 13 in individuals with TB-DM and compared them to those with TB alone (TB) or healthy controls (HC).ResultsCirculating levels of MMP-1, − 2, − 3, − 7, − 10 and − 12 were significantly higher in TB-DM compared to both TB and HC and MMP -13 levels were higher in comparison to HC alone. To understand the effect of standard anti-tuberculosis therapy (ATT) on these MMP levels in TB-DM, we measured the levels of MMPs at the end of treatment (post-treatment). Our findings indicate that ATT is associated with a significant reduction in the levels of MMP-1, − 2, − 3, − 8 and − 13 post-treatment. Moreover, the levels of MMP-1, − 2, − 3, − 9 and − 12 were significantly higher in TB-DM individuals with cavitary disease and/or bilateral disease at baseline but not post-treatment. Similarly, the levels of MMP -1, − 2, − 3 and − 8 exhibited a significant positive relationship with bacterial burden and HbA1c levels at baseline but not post-treatment. Within the TB-DM group, those known to be diabetic before incident TB (KDM) exhibited significantly higher levels of MMP-1, − 2, − 10 and − 12 at baseline and of MMP-1 and -3 post-treatment compared to those newly diagnosed with DM (NDM). Finally, KDM individuals on metformin treatment exhibited significantly lower levels of MMP-1, − 2, − 3, − 7, − 9 and − 12 at baseline and of MMP-7 post-treatment.ConclusionsOur data demonstrate that systemic MMP levels reflect baseline disease severity and extent in TB-DM, differentiate KDM from NDM and are modulated by ATT and metformin therapy.

Co-management of tuberculosis and diabetes: an integrative reviewManejo integrado de la tuberculosis y la diabetes: revisión integrativa

RESUMOObjetivo.Identificar as evidências sobre manejo integrado de tuberculose e diabetes disponíveis na literatura para o contexto latino-americano.Métodos.Foi realizada uma revisão integrativa da literatura com busca nas bases de dados LILACS, Web of Science e PubMed. A estratégia utilizou como termos de busca “tuberculose”, “diabetes mellitus” e “manejo integrado”. Foram incluídos artigos científicos sobre estudos realizados na América Latina, publicados de 2011 a 2017, com acesso livre ao texto integral e publicação em inglês, espanhol ou português. Foram coletados dados relativo aos autores, delineamento, amostra, principais resultados, país e ano da publicação. Finalmente, os estudos foram classificados em níveis de evidência.Resultados.Foram incluídos 20 estudos, dos quais 60% apresentaram baixa evidência científica (nível IV). Conforme esses estudos, os pacientes com diabetes possuem maior risco de desenvolver tuberculose, especialmente aqueles com controle glicêmico ineficaz. Além disso, pacientes com tuberculose-diabetes apresentam atraso na conversão do escarro e maior probabilidade de falha terapêutica e morte. Há maior prevalência da associação tuberculose-diabetes no sexo masculino. Em relação aos registros de tuberculose e diabetes em prontuários ou fichas eletrônicas de informação nos serviços de saúde, há falhas ou ausência de anotações. Foi identificado alto custo financeiro do manejo clínico em indivíduos com a comorbidade. A equipe multidisciplinar possui papel imprescindível na prevenção e promoção em saúde, nos três níveis de atenção.Conclusão.O rastreamento bidirecional de tuberculose-diabetes poderá implicar em melhor controle desses agravos, principalmente em países em desenvolvimento e em áreas endêmicas para tuberculose.

Modern Examination of Tuberculosis-Diabetes Comorbidity

Tuberculosis-diabetes co-morbidity (TB-DM) has been a hurdle in the elimination of tuberculosis worldwide. Individuals with Type 2 diabetes mellitus (T2DM) can become vulnerable to bacterial infections, due to compromised cell mediated immunity [1, 2]. Therefore, individuals with diabetes are at an increased risk for developing an active tuberculosis (TB) disease when infected with Mycobacterium tuberculosis (Mtb). It is estimated that these individuals with T2DM are about three times more likely to develop the active TB compared to individuals without diabetes. Approximately 10% of all TB cases are linked to diabetes and the risk of death from TB is roughly double for those with diabetes, especially in middle to low-income areas [3, 4]. Patients with both T2DM and TB have worse outcomes, including slower bacteria conversion, lower rate of cure, higher chances to relapse, increased risk of mortality, and even escalated drug resistance. While it is known that diabetes causes immune dysfunction, there are still many questions as to how diabetes worsens TB outcomes. It is reported that diabetes might change the appropriate mechanisms of immunological factors that maintain host immune defenses towards infectious agents, the production of specific cytokines, increased formation of reactive oxygen species, as well as reduced levels of the antioxidant glutathione (GSH). In this review, we explore recent research that helps explain the reasons for tuberculosis-diabetes (TB-DM) comorbidity as well as the possible causes for the increased risk of mortality and finally possible prophylactic treatments.

Modulation of iron status biomarkers in tuberculosis-diabetes co-morbidity

Tuberculosis (TB) and diabetes mellitus (DM) remain vital disease burdens in developing countries and the dual burden of DM and TB clearly signifies a growing global public health concern. While modulation of iron status biomarkers in TB is well described, very little is known about the association of these markers with TB-DM. To examine the association of circulating iron status biomarkers in TB disease, we examined the systemic levels of ferritin, hepcidin, soluble transferrin receptor (sTfR), transferrin, apotransferrin and hemopexin in pulmonary TB (PTB) individuals with DM (PTB-DM), without DM (PTB) and those with diabetes only (DM). Circulating levels of ferritin and hepcidin were significantly enhanced in PTB-DM and PTB compared to the DM group. On the other hand, the circulating levels of transferrin and apotransferrin were significantly diminished in PTB–DM and PTB compared to the DM group. The levels of ferritin and hepcidin exhibited a significant positive relationship with HbA1c, whereas apotransferrin exhibited negative relationship with HbA1c in PTB-DM and PTB. ROC analysis revealed that ferritin, hepcidin and transferrin are markers that can distinguish PTB-DM from DM individuals. Our results suggest that some of these circulating iron status markers could prove useful as biomarkers to monitor disease severity.

Heightened circulating levels of antimicrobial peptides in tuberculosis-Diabetes co-morbidity and reversal upon treatment.

BackgroundThe association of antimicrobial peptides (AMPs) with tuberculosis—diabetes comorbidity (PTB-DM) is not well understood.MethodsTo study the association of AMPs with PTB-DM, we examined the systemic levels of cathelicidin (LL37), human beta defensin– 2 (HBD2), human neutrophil peptides 1–3, (HNP1-3) and granulysin in individuals with either PTB-DM, PTB, latent TB (LTB) or no TB infection (NTB).ResultsCirculating levels of cathelicidin and HBD2 were significantly higher and granulysin levels were significantly lower in PTB-DM compared to PTB, LTB or NTB, while the levels of HNP1-3 were significantly higher in PTB-DM compared to LTB or NTB individuals. Moreover, the levels of cathelicidin and/or HBD2 were significantly higher in PTB-DM or PTB individuals with bilateral and cavitary disease and also exhibited a significant positive relationship with bacterial burden. Cathelidin, HBD2 and HNP1-3 levels exhibited a positive relationship with HbA1c and/or fasting blood glucose levels. Finally, anti-tuberculosis therapy resulted in significantly diminished levels of cathelicidin, HBD2, granulysin and significantly enhanced levels of HNP1-3 and granulysin in PTB-DM and/or PTB individuals.ConclusionTherefore, our data demonstrate that PTB-DM is associated with markedly enhanced levels of AMPs and diminished levels of granulysin.

Double Trouble: Prevalence and Factors Associated with Tuberculosis and Diabetes Comorbidity in Bangladesh.

BackgroundDiabetes among tuberculosis patients increases the risk of tuberculosis treatment failure, death, and development of multidrug-resistant tuberculosis. Yet, there is no data is available in Bangladesh on the prevalence of diabetes among tuberculosis patients. The objective of the current study was to estimate prevalence and identify factors associated with tuberculosis-diabetes co-morbidity among TB patients enrolled in the Directly Observed Treatment, Short course program.MethodsA community based cross-sectional quantitative study was conducted among 1910 tuberculosis patients living in six urban and eleven rural areas among whom Oral Glucose Tolerance Test (those who fasted) and Random Blood Sugar test (those who did not fast) were performed. Besides glucose levels, data on socio-demographic information, family history of diabetes and anthropometric measurements (height and weight) were also collected.ResultAmong the 1910 TB patients who participated in screening for diabetes, 245 (12.8%) were found to have diabetes and 296 (15.5%) to have pre-diabetes. Out of those who had diabetes, 34.7% were newly diagnosed through the current study and 65.3% already knew their status. Among those who were found to have prediabetes, 27 (9.1%) had impaired Fasting Blood Glucose (FBG), 230 (77.7%) had Impaired Glucose Tolerance (IGT), and 39 (13.2%) had both Impaired FBG and IGT. Older age, higher BMI, higher education (secondary level and above), being married, participation in less active work, and family history of diabetes are associated with higher prevalence of diabetes.ConclusionWe observed a higher prevalence of diabetes and pre-diabetes in TB patients than reported previously in Bangladesh among the general population which may challenge TB and diabetes control in Bangladesh. Diabetes diagnosis, treatment and care should be integrated in the National TB Program.

Modulation of dendritic cell and monocyte subsets in tuberculosis-diabetes co-morbidity upon standard tuberculosis treatment

Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis (PTB), with development of DM pandemic in countries where tuberculosis (TB) is also endemic. However, the effect of anti-TB treatment on the changes in dentritic cell (DC) and monocyte subset phenotype in TB-DM co-morbidity is not well understood. In this study, we characterized the frequency of DC and monocyte subsets in individuals with PTB with (PTB-DM) or without coincident diabetes mellitus (PTB-NDM) before, during and after completion of anti-TB treatment. PTB-DM is characterized by diminished frequencies of plasmacytoid and myeloid DCs and classical and intermediate monocytes at baseline and 2 months of anti-TB treatment but not following 6 months of treatment completion in comparison to PTB-NDM. DC and monocyte subsets exhibit significant but borderline correlation with fasting blood glucose and glycated hemoglobin levels. Finally, while minor changes in the DC and monocyte compartment were observed at 2 months of treatment, significantly increased frequencies of plasmacytoid and myeloid DCs and classical and intermediate monocytes were observed at the successful completion of anti-TB treatment. Our data show that coincident diabetes alters the frequencies of innate subset distribution of DC and monocytes in TB-DM co-morbidity and suggests that most of these changes are reversible following anti-TB therapy.

Tuberculosis-diabetes co-morbidity is characterized by heightened systemic levels of circulating angiogenic factors

Tuberculosis-diabetes co-morbidity (TB-DM) is characterized by increased inflammation with elevated circulating levels of inflammatory cytokines and other factors. Circulating angiogenic factors are intricately involved in the angiogenesis-inflammation nexus. To study the association of angiogenic factors with TB-DM, we examined the systemic levels of VEGF-A, VEGF-C, VEGF-D, VEGF-R1, VEGF-R2, VEGF-R3 in individuals with either TB-DM (n=44) or TB alone (n=44). Circulating levels of VEGF-A, C, D, R1, R2 and R3 were significantly higher in TB-DM compared to TB individuals. Moreover, the levels of VEGF-A, C, R2 and/or R3 were significantly higher in TB-DM with bilateral or cavitary disease or with hemoptysis, suggesting an association with both disease severity and adverse clinical presentation. The levels of these factors also exhibited a significant positive relationship with bacterial burdens and HbA1c levels. In addition, VEGF-A, C and R2 levels were significantly higher (at 2 months of treatment) in culture positive compared to culture negative TB-DM individuals. Finally, the circulating levels of VEGF-A, C, D, R1, R2 and R3 were significantly reduced following successful chemotherapy at 6 months. Our data demonstrate that TB-DM is associated with heightened levels of circulating angiogenic factors, possibly reflecting both dysregulated angiogenesis and exaggerated inflammation.

Modulation of dendritic cell and monocyte subsets in tuberculosis-diabetes co-morbidity upon standard tuberculosis treatment

Modulation of dendritic cell and monocyte subsets in tuberculosis-diabetes co-morbidity upon standard tuberculosis treatment

Effect of standard tuberculosis treatment on naive, memory and regulatory T-cell homeostasis in tuberculosis-diabetes co-morbidity.

Perturbations in CD4(+) and CD8(+) T-cell phenotype and function are hallmarks of tuberculosis-diabetes co-morbidity. However, their contribution to the pathogenesis of this co-morbidity and the effect of anti-tuberculosis treatment on the phenotype of the T-cell subsets is poorly understood. In this study, we examined the frequency of different T-cell subsets in individuals with pulmonary tuberculosis (PTB) with diabetes mellitus (DM) or without coincident diabetes mellitus (NDM) before, during and after completion of anti-tuberculosis chemotherapy. PTB-DM is characterized by heightened frequencies of central memory CD4(+) and CD8(+) T cells and diminished frequencies of naive, effector memory and/or effector CD4(+) and CD8(+) T cells at baseline and after 2months of treatment but not following treatment completion in comparison with PTB-NDM. Central memory CD4(+) and CD8(+) T-cell frequencies exhibited a positive correlation with fasting blood glucose and glycated haemoglobin A1c levels, whereas the frequencies of naive and effector memory or effector CD4(+) and CD8(+) T cells exhibited a negative correlation. However, the frequencies of CD4(+) and CD8(+) T-cell subsets in individuals with PTB exhibited no significant relationship with bacterial burdens. Finally, although minor alterations in the T-cell subset compartment were observed at 2months of treatment, significantly decreased frequencies of central memory and significantly enhanced frequencies of naive CD4(+) and CD8(+) T cells were observed at the completion of treatment. Our data reveal a profound effect of coexistent diabetes on the altered frequencies of central memory, effector memory and naive T cells and its normalization following therapy.