The Influence of Diabetes, Glycemic Control, and Diabetes-Related Comorbidities on Pulmonary Tuberculosis

PLOS ONE, Dec 2019

Background To assess the influence of diabetes mellitus (DM), glycemic control, and diabetes-related comorbidities on manifestations and outcome of treatment of pulmonary tuberculosis (TB). Methodology/Principal Findings Culture positive pulmonary TB patients notified to health authorities in three hospitals in Taiwan from 2005–2010 were investigated. Glycemic control was assessed by glycated haemoglobin A1C (HbA1C) and diabetic patients were categorized into 3 groups: HbA1C<7%, HbA1C 7–9%, HbA1C>9%. 1,473 (705 with DM and 768 without DM) patients were enrolled. Of the 705 diabetic patients, 82 (11.6%) had pretreatment HbA1C<7%, 152 (21.6%) 7%–9%, 276 (39.2%) >9%, and 195 (27.7%) had no information of HbA1C. The proportions of patients with any symptom, cough, hemoptysis, tiredness and weight loss were all highest in diabetic patients with HbA1C>9%. In multivariate analysis adjusted for age, sex, smoking, and drug resistance, diabetic patients with HbA1C>9% (adjOR 3.55, 95% CI 2.40–5.25) and HbA1C 7–9% (adjOR 1.62, 95% CI 1.07–2.44) were significantly more likely to be smear positive as compared with non-diabetic patients, but not those with HbA1C<7% (adjOR 1.16, 95% CI 0.70–1.92). The influence of DM on outcome of TB treatment was not proportionately related to HbA1C, but mainly mediated through diabetes-related comorbidities. Patients with diabetes-related comorbidities had an increased risk of unfavorable outcome (adjOR 3.38, 95% CI 2.19–5.22, p<0.001) and one year mortality (adjOR 2.80, 95% CI 1.89–4.16). However, diabetes was not associated with amplification of resistance to isoniazid (p = 0.363) or to rifampicin (p = 0.344). Conclusions/Significance Poor glycemic control is associated with poor TB treatment outcome and improved glycemic control may reduce the influence of diabetes on TB.

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The Influence of Diabetes, Glycemic Control, and Diabetes-Related Comorbidities on Pulmonary Tuberculosis

March The Influence of Diabetes, Glycemic Control, and Diabetes-Related Comorbidities on Pulmonary Tuberculosis Chen Yuan Chiang 0 1 2 Kuan Jen Bai 0 1 2 Hsien Ho Lin 0 1 2 Shun Tien Chien 0 1 2 Jen Jyh Lee 0 1 2 Donald A. Enarson 0 1 2 Ting-I Lee 0 1 2 Ming-Chih Yu 0 1 2 0 1 International Union Against Tuberculosis and Lung Disease, Paris, France, 2 Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University , Taipei, Taiwan , 3 Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University , Taipei, Taiwan , 4 School of Respiratory Therapy, College of Medicine, Taipei Medical University , Taipei, Taiwan , 5 Institute of Epidemiology and Preventive Medicine, National Taiwan University , Taipei, Taiwan , 6 Chest Hospital, Department of Health, Tainan County, Taiwan, 7 Department of Internal Medicine, Tzu Chi General Hospital and Tzu Chi University , Hualien, Taiwan , 8 Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University , Taipei, Taiwan , 9 Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University , Taipei , Taiwan 1 Funding: The work was supported by Taiwan Centers of Disease Control [grant number a research grant DOH101-DC-1103]. The sponsor of the study had no role in study design , data collection, data analysis, data interpretation, or writing of the report 2 Academic Editor: Norikazu Maeda, Graduate School of Medicine, Osaka University , JAPAN - Competing Interests: The authors have declared that no competing interests exist. To assess the influence of diabetes mellitus (DM), glycemic control, and diabetes-related comorbidities on manifestations and outcome of treatment of pulmonary tuberculosis (TB). Methodology/Principal Findings Culture positive pulmonary TB patients notified to health authorities in three hospitals in Taiwan from 20052010 were investigated. Glycemic control was assessed by glycated haemoglobin A1C (HbA1C) and diabetic patients were categorized into 3 groups: HbA1C<7%, HbA1C 79%, HbA1C>9%. 1,473 (705 with DM and 768 without DM) patients were enrolled. Of the 705 diabetic patients, 82 (11.6%) had pretreatment HbA1C<7%, 152 (21.6%) 7%9%, 276 (39.2%) >9%, and 195 (27.7%) had no information of HbA1C. The proportions of patients with any symptom, cough, hemoptysis, tiredness and weight loss were all highest in diabetic patients with HbA1C>9%. In multivariate analysis adjusted for age, sex, smoking, and drug resistance, diabetic patients with HbA1C>9% (adjOR 3.55, 95% CI 2.405.25) and HbA1C 79% (adjOR 1.62, 95% CI 1.072.44) were significantly more likely to be smear positive as compared with non-diabetic patients, but not those with HbA1C<7% (adjOR 1.16, 95% CI 0.701.92). The influence of DM on outcome of TB treatment was not proportionately related to HbA1C, but mainly mediated through diabetes-related comorbidities. Patients with diabetes-related comorbidities had an increased risk of unfavorable outcome (adjOR 3.38, 95% CI 2.195.22, p<0.001) and one year mortality (adjOR 2.80, 95% CI 1.894.16). However, diabetes was not associated with amplification of resistance to isoniazid (p = 0.363) or to rifampicin (p = 0.344). Conclusions/Significance Poor glycemic control is associated with poor TB treatment outcome and improved glycemic control may reduce the influence of diabetes on TB. The International Diabetes Federation has estimated that the number of people living with diabetes mellitus (DM) worldwide has been increasing and will rise to 592 million by 2035.[1] Several studies have shown that DM is associated with an increased risk of tuberculosis (TB).[2] A recent meta-analysis reported that the relative risk of TB in diabetic patients was 3.11 (95% CI 2.274.26) as compared with individuals without DM in cohort studies.[3] The potential impact of a rising epidemic of DM on TB has been raised in several articles.[46] To address the dual challenge of DM and TB, the World Health Organization and the International Union Against Tuberculosis and Lung Disease have recently published a collaborative framework for care and control of TB and DM.[7] The influence of DM on clinical manifestations and outcome of treatment of pulmonary TB has previously been reported. [813] However, the results reported by different researchers have not been consistent. Leung et al reported that the risk of TB in elderly diabetic patients was associated with glycemic control.[14] As clinical manifestations of pulmonary TB are likely related to immune status and hyperglycemia is associated with changes of immune response, we hypothesized that the influence of DM on clinical manifestations of pulmonary TB is related to glycemic control.[15, 16] As complications of chronic hyperglycemia may have an impact on outcome of TB treatment, we further hypothesized that this effect is mediated through diabetes-related comorb (...truncated)


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Chen Yuan Chiang, Kuan Jen Bai, Hsien Ho Lin, Shun Tien Chien, Jen Jyh Lee, Donald A. Enarson, Ting-I Lee, Ming-Chih Yu. The Influence of Diabetes, Glycemic Control, and Diabetes-Related Comorbidities on Pulmonary Tuberculosis, PLOS ONE, 2015, Volume 10, Issue 3, DOI: 10.1371/journal.pone.0121698