A double burden of tuberculosis and diabetes mellitus and the role of vitamin D deficiency

Qiuzhen Wang

Research output: Thesisinternal PhD, WU

Abstract

Tuberculosis remains a major global health challenge, particularly in low-to-middle income countries such as China. At the same time, the country is facing a rapidly increasing diabetes incidence over the last 10 years. Diabetes aggravates the tuberculosis epidemic which poses a serious challenge in public health. In recent years, the high prevalence of vitamin D deficiency represents a global health problem, which is also associated with the risk of diabetes, and tuberculosis. Therefore, we carried out this study aimed to investigate the epidemiology of co-occurrence of tuberculosis and diabetes and to elucidate the role of vitamin D deficiency.

In a rural area setting in Linyi, Shandong, China, 6382 active tuberculosis patients, together with 6674 non-tuberculosis controls were screened for diabetes. The prevalence of diabetes in tuberculosis was 6.3%, nearly 35% higher than controls. Tuberculosis was independently associated with about three times higher risk of having diabetes. Hyperglycemia was found to be associated with a nearly two-fold higher probability of patient delay of tuberculosis in a randomly selected subgroup from this study. Compared with the highest quartile, subjects in the lowest quartile of serum 25(OH)D had a more than four-fold and two-fold increased risk of having tuberculosis, and concurrent tuberculosis and diabetes. Subsequently, a city level hospital-based study was carried out. A high prevalence of vitamin D deficiency of nearly 80% was observed in tuberculosis patients, and serum 25(OH)D was observed to be inversely associated with TNF-α, while positively associated with leptin, indicating a possible immune-modulatory mechanism of vitamin D. In the intervention trial of vitamin D3 (800IU/d), 358 newly diagnosed tuberculosis patients were included and more severe signs and symptoms at presentation were observed in those with diabetes. Vitamin D showed a favourable adjunctive effect on clinical manifestations in this subgroup, while no similar effects were found in patients with tuberculosis only.

In conclusion, active tuberculosis patients had an increased risk of having diabetes, as well as prevalent hypovitaminosis D. Vitamin D showed an adjunctive effect in the therapy, i.e., improvement of tuberculosis clinical manifestations in patients with combined diabetes and tuberculosis. Our study provides possible etiological clues for the combined diseases, and the possible role of vitamin D deficiency. We recommend bidirectional screening for tuberculosis and diabetes, especially early detection of tuberculosis in diabetes patients; and health education to increase awareness of the double burden. In addition, vitamin D supplementation may benefit tuberculosis patients in general. Moreover, extra vitamin D may benefit the general population especially in a situation of a heavy tuberculosis burden combined with prevalent vitamin D deficiency. We suggest future studies to address long-term treatment outcomes of patients with the combined diseases and to define certain markers to set up a prognostic model. Also, longitudinal studies to verify the role of vitamin D deficiency in the double burden, and confirmative trials on the effect of vitamin D supplementation are needed.

Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
Supervisors/Advisors
  • Kok, Frans, Promotor
  • Schouten, E.G., Co-promotor
  • Ma, A., Co-promotor
Award date23 Apr 2019
Place of PublicationWageningen
Publisher
Print ISBNs9789463439039
DOIs
Publication statusPublished - 2019

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Vitamin D Deficiency
Diabetes Mellitus
Tuberculosis
Vitamin D
China

Cite this

Wang, Qiuzhen. / A double burden of tuberculosis and diabetes mellitus and the role of vitamin D deficiency. Wageningen : Wageningen University, 2019. 221 p.
@phdthesis{f7e731ddcaaa43bd912451fd3b23f671,
title = "A double burden of tuberculosis and diabetes mellitus and the role of vitamin D deficiency",
abstract = "Tuberculosis remains a major global health challenge, particularly in low-to-middle income countries such as China. At the same time, the country is facing a rapidly increasing diabetes incidence over the last 10 years. Diabetes aggravates the tuberculosis epidemic which poses a serious challenge in public health. In recent years, the high prevalence of vitamin D deficiency represents a global health problem, which is also associated with the risk of diabetes, and tuberculosis. Therefore, we carried out this study aimed to investigate the epidemiology of co-occurrence of tuberculosis and diabetes and to elucidate the role of vitamin D deficiency. In a rural area setting in Linyi, Shandong, China, 6382 active tuberculosis patients, together with 6674 non-tuberculosis controls were screened for diabetes. The prevalence of diabetes in tuberculosis was 6.3{\%}, nearly 35{\%} higher than controls. Tuberculosis was independently associated with about three times higher risk of having diabetes. Hyperglycemia was found to be associated with a nearly two-fold higher probability of patient delay of tuberculosis in a randomly selected subgroup from this study. Compared with the highest quartile, subjects in the lowest quartile of serum 25(OH)D had a more than four-fold and two-fold increased risk of having tuberculosis, and concurrent tuberculosis and diabetes. Subsequently, a city level hospital-based study was carried out. A high prevalence of vitamin D deficiency of nearly 80{\%} was observed in tuberculosis patients, and serum 25(OH)D was observed to be inversely associated with TNF-α, while positively associated with leptin, indicating a possible immune-modulatory mechanism of vitamin D. In the intervention trial of vitamin D3 (800IU/d), 358 newly diagnosed tuberculosis patients were included and more severe signs and symptoms at presentation were observed in those with diabetes. Vitamin D showed a favourable adjunctive effect on clinical manifestations in this subgroup, while no similar effects were found in patients with tuberculosis only. In conclusion, active tuberculosis patients had an increased risk of having diabetes, as well as prevalent hypovitaminosis D. Vitamin D showed an adjunctive effect in the therapy, i.e., improvement of tuberculosis clinical manifestations in patients with combined diabetes and tuberculosis. Our study provides possible etiological clues for the combined diseases, and the possible role of vitamin D deficiency. We recommend bidirectional screening for tuberculosis and diabetes, especially early detection of tuberculosis in diabetes patients; and health education to increase awareness of the double burden. In addition, vitamin D supplementation may benefit tuberculosis patients in general. Moreover, extra vitamin D may benefit the general population especially in a situation of a heavy tuberculosis burden combined with prevalent vitamin D deficiency. We suggest future studies to address long-term treatment outcomes of patients with the combined diseases and to define certain markers to set up a prognostic model. Also, longitudinal studies to verify the role of vitamin D deficiency in the double burden, and confirmative trials on the effect of vitamin D supplementation are needed.",
author = "Qiuzhen Wang",
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A double burden of tuberculosis and diabetes mellitus and the role of vitamin D deficiency. / Wang, Qiuzhen.

Wageningen : Wageningen University, 2019. 221 p.

Research output: Thesisinternal PhD, WU

TY - THES

T1 - A double burden of tuberculosis and diabetes mellitus and the role of vitamin D deficiency

AU - Wang, Qiuzhen

N1 - WU thesis 7201 Includes bibliographical references. - With summary in English

PY - 2019

Y1 - 2019

N2 - Tuberculosis remains a major global health challenge, particularly in low-to-middle income countries such as China. At the same time, the country is facing a rapidly increasing diabetes incidence over the last 10 years. Diabetes aggravates the tuberculosis epidemic which poses a serious challenge in public health. In recent years, the high prevalence of vitamin D deficiency represents a global health problem, which is also associated with the risk of diabetes, and tuberculosis. Therefore, we carried out this study aimed to investigate the epidemiology of co-occurrence of tuberculosis and diabetes and to elucidate the role of vitamin D deficiency. In a rural area setting in Linyi, Shandong, China, 6382 active tuberculosis patients, together with 6674 non-tuberculosis controls were screened for diabetes. The prevalence of diabetes in tuberculosis was 6.3%, nearly 35% higher than controls. Tuberculosis was independently associated with about three times higher risk of having diabetes. Hyperglycemia was found to be associated with a nearly two-fold higher probability of patient delay of tuberculosis in a randomly selected subgroup from this study. Compared with the highest quartile, subjects in the lowest quartile of serum 25(OH)D had a more than four-fold and two-fold increased risk of having tuberculosis, and concurrent tuberculosis and diabetes. Subsequently, a city level hospital-based study was carried out. A high prevalence of vitamin D deficiency of nearly 80% was observed in tuberculosis patients, and serum 25(OH)D was observed to be inversely associated with TNF-α, while positively associated with leptin, indicating a possible immune-modulatory mechanism of vitamin D. In the intervention trial of vitamin D3 (800IU/d), 358 newly diagnosed tuberculosis patients were included and more severe signs and symptoms at presentation were observed in those with diabetes. Vitamin D showed a favourable adjunctive effect on clinical manifestations in this subgroup, while no similar effects were found in patients with tuberculosis only. In conclusion, active tuberculosis patients had an increased risk of having diabetes, as well as prevalent hypovitaminosis D. Vitamin D showed an adjunctive effect in the therapy, i.e., improvement of tuberculosis clinical manifestations in patients with combined diabetes and tuberculosis. Our study provides possible etiological clues for the combined diseases, and the possible role of vitamin D deficiency. We recommend bidirectional screening for tuberculosis and diabetes, especially early detection of tuberculosis in diabetes patients; and health education to increase awareness of the double burden. In addition, vitamin D supplementation may benefit tuberculosis patients in general. Moreover, extra vitamin D may benefit the general population especially in a situation of a heavy tuberculosis burden combined with prevalent vitamin D deficiency. We suggest future studies to address long-term treatment outcomes of patients with the combined diseases and to define certain markers to set up a prognostic model. Also, longitudinal studies to verify the role of vitamin D deficiency in the double burden, and confirmative trials on the effect of vitamin D supplementation are needed.

AB - Tuberculosis remains a major global health challenge, particularly in low-to-middle income countries such as China. At the same time, the country is facing a rapidly increasing diabetes incidence over the last 10 years. Diabetes aggravates the tuberculosis epidemic which poses a serious challenge in public health. In recent years, the high prevalence of vitamin D deficiency represents a global health problem, which is also associated with the risk of diabetes, and tuberculosis. Therefore, we carried out this study aimed to investigate the epidemiology of co-occurrence of tuberculosis and diabetes and to elucidate the role of vitamin D deficiency. In a rural area setting in Linyi, Shandong, China, 6382 active tuberculosis patients, together with 6674 non-tuberculosis controls were screened for diabetes. The prevalence of diabetes in tuberculosis was 6.3%, nearly 35% higher than controls. Tuberculosis was independently associated with about three times higher risk of having diabetes. Hyperglycemia was found to be associated with a nearly two-fold higher probability of patient delay of tuberculosis in a randomly selected subgroup from this study. Compared with the highest quartile, subjects in the lowest quartile of serum 25(OH)D had a more than four-fold and two-fold increased risk of having tuberculosis, and concurrent tuberculosis and diabetes. Subsequently, a city level hospital-based study was carried out. A high prevalence of vitamin D deficiency of nearly 80% was observed in tuberculosis patients, and serum 25(OH)D was observed to be inversely associated with TNF-α, while positively associated with leptin, indicating a possible immune-modulatory mechanism of vitamin D. In the intervention trial of vitamin D3 (800IU/d), 358 newly diagnosed tuberculosis patients were included and more severe signs and symptoms at presentation were observed in those with diabetes. Vitamin D showed a favourable adjunctive effect on clinical manifestations in this subgroup, while no similar effects were found in patients with tuberculosis only. In conclusion, active tuberculosis patients had an increased risk of having diabetes, as well as prevalent hypovitaminosis D. Vitamin D showed an adjunctive effect in the therapy, i.e., improvement of tuberculosis clinical manifestations in patients with combined diabetes and tuberculosis. Our study provides possible etiological clues for the combined diseases, and the possible role of vitamin D deficiency. We recommend bidirectional screening for tuberculosis and diabetes, especially early detection of tuberculosis in diabetes patients; and health education to increase awareness of the double burden. In addition, vitamin D supplementation may benefit tuberculosis patients in general. Moreover, extra vitamin D may benefit the general population especially in a situation of a heavy tuberculosis burden combined with prevalent vitamin D deficiency. We suggest future studies to address long-term treatment outcomes of patients with the combined diseases and to define certain markers to set up a prognostic model. Also, longitudinal studies to verify the role of vitamin D deficiency in the double burden, and confirmative trials on the effect of vitamin D supplementation are needed.

U2 - 10.18174/472258

DO - 10.18174/472258

M3 - internal PhD, WU

SN - 9789463439039

PB - Wageningen University

CY - Wageningen

ER -