Prevalence of dysglycemia and clinical presentation of pulmonary tuberculosis in Western India

Mave, Vidya; Meshram, Shailesh; Lokhande, Rahul; Kadam, Dileep; Dharmshale, Sujata; Bharadwaj, Renu; Kagal, Anju; Pradhan, Neeta; Deshmukh, Sanjay D; Atre, Sachin; Sahasrabudhe, Tushar; Barthwal,; Kakrani, Arjun; Kulkarni, Vandana; Raskar, Swapnil; Suryavanshi, Nishi; Shivakoti, Rupak; Chon, Sandy; Selvin, Elizabeth; Gupte, Akshay; Gupta, Amita; Gupte, Nikhil; Golub, Jonathan E.

doi:10.5588/ijtld.17.0474

Cited by 23 publications

(25 citation statements)

References 24 publications

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“…Pune, India has a population of 7 million within the city and surrounding semi-urban/rural areas and a TB notification incidence of 112–132/100 000 person-years (PY) [ 16 ]. In this setting, over half of TB cases are dysglycemic, and the mycobacterial burden before TB treatment initiation is 4-fold higher in patients with DM [ 17 ]. We hypothesized that, due to higher baseline mycobacterial burden and altered immune response to TB [ 18 ], DM would lead to prolonged sputum culture positivity and higher risk of TB treatment failure, recurrence, or death.…”

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confidence: 99%

Diabetes Mellitus and Tuberculosis Treatment Outcomes in Pune, India

Mave

Gaikwad

Barthwal

et al. 2021

Open Forum Infectious Diseases

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Background Diabetes mellitus (DM) increases the risk of tuberculosis (TB) disease. Knowledge of the impact of DM on TB treatment outcomes is primarily based on retrospective studies. Methods We conducted a prospective cohort study of new pulmonary TB patients with and without DM (TB-DM and TB-only) in India. The association of DM with a composite unfavorable TB treatment outcome (failure, recurrence, mortality) over 18 months was determined and the effect of DM on all-cause mortality and early mortality (death during TB treatment) was assessed. Results Of 799 participants, 574(72%) had TB-only and 225(28%) had TB-DM. The proportion of patients with DM who experienced the composite outcome was 20% as compared to 21% for TB only participants (adjusted hazard ratio 1.13, 95% CI 0.75–1.70). Mortality was higher in participants with DM (10% vs. 7%), and early mortality was substantially higher among patients with DM (adjusted hazard ratio [aHR] 4.36; 95% CI:1·62–11.76). Conclusion DM was associated with early mortality in this prospective cohort study, but overall unfavorable outcomes were similar to participants without DM. Interventions to reduce mortality during TB treatment among people with TB-DM are needed.

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Diabetes Mellitus and Tuberculosis Treatment Outcomes in Pune, India

Mave

Gaikwad

Barthwal

et al. 2021

Open Forum Infectious Diseases

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“…In a parallel study conducted within the TANDEM Consortium analysis involving patients from the same 4 countries, TB patients with IH as well as with DM were more likely to be sputum smear positive compared to normoglycemic TB controls [ 24 ]. The impact of IH on TB disease susceptibility has been less well investigated, but in 2 studies conducted in India [ 15 , 36 ] and 1 in Kenya [ 37 ], both IH and diabetes prevalences in patients with pulmonary TB were substantially higher than in the general population, indicating that IH is also associated with the development of active TB. Our data strongly indicate that immune abnormalities occurring in DM-TB are already present in IH-TB, and it is possible that existing altered immune function in hyperglycemia underlies the epidemiological link.…”

Section: Discussionmentioning

confidence: 99%

Impact of Intermediate Hyperglycemia and Diabetes on Immune Dysfunction in Tuberculosis

Eckold

Kumar

Weiner

et al. 2020

Clinical Infectious Diseases

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Background People living with diabetes have an increased risk of developing active tuberculosis and are more likely to have poor tuberculosis-treatment outcomes, which may impact on control of tuberculosis as the prevalence of diabetes is increasing worldwide. Blood transcriptomes are altered in active tuberculosis patients relative to healthy individuals. The effects of diabetes and intermediate hyperglycaemia on this transcriptomic signature were investigated to enhance understanding of immunological susceptibility in diabetes-tuberculosis comorbidity. Methods Whole blood samples were collected from active tuberculosis patients with diabetes (HbA1c ≥6.5%) or intermediate hyperglycaemia (HbA1c 5.7-6.5%), tuberculosis-only patients and healthy controls in four countries: South Africa, Romania, Indonesia and Peru. Differential blood gene expression was determined by RNA-seq (n=249). Results Diabetes increased the magnitude of gene expression change in the host transcriptome in tuberculosis, notably showing an increase in genes associated with innate inflammatory and decrease in adaptive immune responses. Strikingly, patients with intermediate hyperglycaemia and tuberculosis exhibited blood transcriptomes much more similar to diabetes-tuberculosis patients than to patients with only tuberculosis. Both diabetes-tuberculosis and intermediate hyperglycaemia-tuberculosis patients had a decreased type I interferon response relative to tuberculosis-only patients. Conclusions Co-morbidity in individuals with both tuberculosis and diabetes is associated with altered transcriptomes, with an expected enhanced inflammation in the presence of both conditions, but also reduced type 1 interferon responses in co-morbid patients, suggesting an unexpected uncoupling of the TB transcriptome phenotype. These immunological dysfunctions are also present in individuals with intermediate hyperglycaemia, showing that altered immunity to tuberculosis may also be present in this group. The TB disease outcomes in individuals with intermediate hyperglycaemia diagnosed with TB should be investigated further.

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“…Study procedures. Patients with newly diagnosed pulmonary TB were screened for DM as part of a prospective cohort study in which patients with and without DM initiating treatment for TB were followed for treatment outcomes (69). Study participants received standard TB treatment through the RNTCP.…”

Section: Methodsmentioning

confidence: 99%

Effect of Diabetes Mellitus on the Pharmacokinetics and Pharmacodynamics of Tuberculosis Treatment

Alfarisi

Mave

Gaikwad

et al. 2018

Antimicrob Agents Chemother

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Diabetes mellitus (DM) and tuberculosis (TB) are two common diseases with increasing geographic overlap and clinical interactions. The effect of DM and hemoglobin A1c (HbA1c) values on the pharmacokinetics (PK) and pharmacodynamics (PD) of anti-TB drugs remains poorly characterized. Newly diagnosed TB patients with and without DM starting fixed-dose, thrice-weekly treatment underwent sampling for PK assessments (predose and 0.5, 2, and 6 h postdose) during the intensive and continuation phases of treatment. The effect of DM and HbA1c values on the maximum concentration ( ) of rifampin, isoniazid, and pyrazinamide and the association between drug concentrations and microbiologic and clinical outcomes were assessed. Of 243 patients, 101 had DM. Univariate analysis showed significant reductions in the of pyrazinamide and isoniazid (but not rifampin) with DM or increasing HbA1c values. After adjusting for age, sex, and weight, DM was associated only with reduced pyrazinamide concentrations (adjusted geometric mean ratio = 0.74, = 0.03). In adjusted Cox models, female gender (adjusted hazards ratio [aHR] = 1.75, = 0.001), a lower smear grade with the Xpert assay (aHR = 1.40, < 0.001), and the pyrazinamide (aHR = 0.99, = 0.006) were independent predictors of sputum culture conversion to negative. Higher isoniazid or rifampin concentrations were associated with a faster time to culture conversion in patients with DM only. A pyrazinamide above the therapeutic target was associated with higher unfavorable outcomes (treatment failure, relapse, death) (odds ratio = 1.92, = 0.04). DM and higher HbA1c values increased the risk of not achieving therapeutic targets for pyrazinamide (but not rifampin or isoniazid). Higher pyrazinamide concentrations, though, were associated with worse microbiologic and clinical outcomes. DM status also appeared to influence PK-PD relationships for isoniazid and rifampin.

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Prevalence of dysglycemia and clinical presentation of pulmonary tuberculosis in Western India

Cited by 23 publications

References 24 publications

Diabetes Mellitus and Tuberculosis Treatment Outcomes in Pune, India

Diabetes Mellitus and Tuberculosis Treatment Outcomes in Pune, India

Impact of Intermediate Hyperglycemia and Diabetes on Immune Dysfunction in Tuberculosis

Effect of Diabetes Mellitus on the Pharmacokinetics and Pharmacodynamics of Tuberculosis Treatment

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