Dietary patterns and the risk of tuberculosis-drug-induced liver injury: a cohort study.

Background and purpose: Nutrition is associated with tuberculosis drug-induced liver injury (TBLI). How dietary patterns relate to tuberculosis drug-induced liver injury is still unknown. The objective of this study is to explore the relation between dietary patterns and the risk of tuberculosis drug-induced liver injury. Methods: This cohort study was conducted at two hospitals in Shandong Province, China, between 2011 and 2013. A total of 605 tuberculosis patients were included in the final analysis. The blood aspartate aminotransferase or alanine aminotransferase level was monitored through the 6-month tuberculosis treatment. The semi-quantitative food frequency questionnaires were used to survey dietary intake in the second month of the tuberculosis treatment. The China Healthy Diet Index (CHDI), which was previously validated in the Chinese population, was used as an a priori dietary pattern. A posteriori dietary patterns were extracted by principal component analysis (PCA). Results: The CHDI was negatively associated with the risk of liver injury [adjusted odds ratio (aOR) per standard deviation (SD) (95% CI): 0.61 (0.40-0.94)] and liver dysfunction [aOR per SD (95% CI): 0.47 (0.35-0.64)] in the multivariate logistic model. A positive association between "Organ meat, poultry, and vegetable oil" dietary pattern scores (extracted by PCA) and the risk of liver injury [aOR (95% CI): 3.02 (1.42-6.41)] and liver dysfunction [aOR (95% CI): 1.83 (1.09-3.05)] was observed. Conclusion: In conclusion, a high CHDI score was a protective factor for tuberculosis drug-induced liver injury, while the "Organ meat, poultry, and vegetable oil" dietary pattern, which was rich in organ meat, poultry, and vegetable oil and low in vegetables, was an independent risk factor for tuberculosis drug-induced liver injury.

Association between macronutrients intake and liver dysfunction among tuberculosis patients in rural China.

BACKGROUND AND OBJECTIVES: Macronutrients play a vital role in liver dysfunction and affect tuberculosis treatment and prognosis. However, macronutrients intake was inadequate for most tuberculosis patients. This study aimed to clarify the associations between macronutrients intake or energy percentages and liver dys-function in tuberculosis patients. METHODS AND STUDY DESIGN: In this cross-sectional study, 2581 active tu-berculosis patients aged ≥18 years were included from local tuberculosis clinics in Linyi, China. Macronutrients intake and energy percentages were assessed by 24-hour dietary recalls. The concentration of alanine transferase (ALT) or aspartate transaminase (AST) greater than 40 U/L was defined as liver dysfunction. A restricted cubic spline (RCS) was applied to determine the dose-response relationships. RESULTS: Liver dysfunction was assessed for 14.6% (377 patients) of tuberculosis patients. Higher protein (Q2-Q4 in model 1 and 2) or fat intake and fat-to-energy percentages and lower carbohydrate-to-energy percentages (Q4 in model 1) were associated with a decreased incidence of liver dysfunction (p-trend < 0.05). Among those who were male, normal BMI, or consumed energy <1636 kcal/d, inverse associations between protein or fat intake and the risks of liver dysfunction in models were suggested (p-trend < 0.05). Moreover, J-shaped curves in RCS were evident in liver dysfunction tuberculosis patients with protein or fat intake (p-nonlinearity < 0.05). Conclu-sions: Significant linear associations between macronutrients intake or energy percentages and liver dysfunction prevalence were found only in male, normal BMI, or less energy intake patients. The shapes of liver dysfunction-morbidity differed significantly by macronutrients intake or energy percentage.

Lactobacillus casei modulates inflammatory cytokines and metabolites during tuberculosis treatment: A post hoc randomized controlled trial.

BACKGROUND AND OBJECTIVES: Inflammatory cytokines and metabolic abnormalities are common in patients with tuberculosis. Observational studies have indicated that probiotics modulate inflammatory cytokines and metabolites; however, clinical evidence of the effect of probiotics on patients with tuberculosis is lacking. This study investigated the effects of Lactobacillus casei on inflammatory cytokines and metabolites during tuberculosis treatment. METHODS AND STUDY DESIGN: A randomized controlled trial was conducted. A total of 47 inpatients were included and randomly assigned to receive standard antituberculosis therapy only (control group) or that treatment together with 1 × 1010 colony-forming units per day of Lactobacillus casei (low-dose group) or 2 × 1010 colony-forming units per day of Lactobacillus casei (high-dose group) for 4 weeks of intensive treatment during hospitalization. Plasma samples were analyzed for inflammatory cytokines and metabolomics with ELISA kits and ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry. RESULTS: Daily Lactobacillus casei supplementation of up to 2 × 1010 colony-forming units significantly lowered the concentrations of tumor necrosis factor-α, interleukin-6, interleukin-10, and interleukin-12 (p=0.007, p=0.042, p=0.002, p<0.001, respectively) in patients with tuberculosis. Compared with the control and low-dose groups, the plasma metabolites of phosphatidylserine, maresin 1, phosphatidylcholine, L-saccharopine, and pyridoxamine were significantly upregulated, and N-acetylmethionine, L-tryptophan, phosphatidylethanolamine, and phenylalanine were downregulated in the high-dose group. Strong correlations were observed between metabolites and inflammatory cytokines. CONCLUSIONS: Lactobacillus casei supplementation during the intensive phase of tuberculosis treatment can significantly modulate inflammatory cytokines and metabolites. Decreased inflammatory cytokines may be related to metabolite changes.

Poor diet quality evaluated with the China Healthy Diet Index in Chinese tuberculosis patients.

OBJECTIVE: The purpose of this study was to compare and evaluate the diet quality of tuberculosis patients and healthy adults by using the China Healthy Diet Index (CHDI) and to provide guidance for the diet of tuberculosis patients in the future. METHODS: A case-control study of 1241 patients and 1241 healthy individuals matchedfor sex and age. The CHDI was used to score the overall diet quality of patients in the casegroup and the control group. RESULTS: The CHDI score of tuberculosis patients was 61.61 and that of healthy controls was 63.97. After adjustment for confounders, participants with >80 on CHDI were 73.5% less likely to develop tuberculosis than participants with <51 (OR: 0.265, 95% CI: 0.086, 0.813, p < 0.05). In the original model, the CHDI scores in the highest range were inversely associated with tuberculosis risk compared with the lowest range (OR: 0.687, 95% CI: 0.420,1.122, p < 0.001). After adjusting for confounders, the CHDI score was significantly associated with a reduced risk of tuberculosis (OR: 0.265, 95% CI: 0.086, 0.813, p < 0.001). After adjusting for confounders, a high-quality diet was positively correlated with anti-tuberculosis treatment outcomes (OR:0.957, 95% CI: 0.918,0.998, p = 0.039). CONCLUSION: Compared with healthy adults, tuberculosis patients have poor diet quality with unreasonable diet structure. The insufficient intake of whole grains, vegetables, beans, aquatic products, meat and eggs and the excessive intake of pure energy food and solid fat suggests that the dietary structure of tuberculosis patients was unreasonable. This study provides an idea of the diet structure of tuberculosis patients.

Dietary Intake of Vegetables and Cooking Oil Was Associated With Drug-Induced Liver Injury During Tuberculosis Treatment: A Preliminary Cohort Study.

Background and Purpose: Drug-induced liver injury is challenging during tuberculosis treatment. There is no epidemiological data investigating the relation between dietary intake and the risk of drug-induced liver injury during tuberculosis treatment. The aim of this study is to investigate the association of food and nutrient intake with the incidence of tuberculosis-drug-induced liver injury. Methods: A cohort study was conducted in two city-level tuberculosis-specialized hospitals in Linyi City and Qingdao City, China from January 2011 to December 2013. The dietary intake was assessed by a 3-day 24-h food recall survey and a standard food-frequency questionnaire. The liver functions including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were monitored throughout the 6-month tuberculosis therapy. Liver injury was defined as ALT or AST higher than two times of the upper limit of normal (ULN). Liver dysfunction was defined as ALT or AST higher than the ULN. The ULN for ALT and AST is 40 U/L. Multivariate logistic regression analyses were performed to determine the dietary factors associated with the incidence of liver injury and liver dysfunction. Results: A total of 605 patients were included in the analysis. During the treatment, 8.1% patients exhibited liver injury and 23.3% patients exhibited liver dysfunction. A lower intake of vegetables was associated with a higher risk of liver injury [OR (95% CI): 3.50 (1.52-8.08), P = 0.003) and liver dysfunction [OR (95% CI): 2.37 (1.31-4.29), P = 0.004], while a lower intake of cooking oil was associated with a lower risk of liver injury [OR (95% CI): 0.44 (0.20-0.96), P = 0.040)] and liver dysfunction [OR (95% CI): 0.51 (0.31-0.85), P = 0.009]. Conclusion: The current study indicated that the higher risks of tuberculosis-drug-induced liver injury and liver dysfunction were statistically associated with decreased vegetable intake and increased cooking oil intake.

Lactobacillus casei Alleviated the Abnormal Increase of Cholestasis-Related Liver Indices During Tuberculosis Treatment: A Post Hoc Analysis of Randomized Controlled Trial.

SCOPE: Probiotics are promising in mitigating drug-induced liver injury in animal experiments. However, the clinical evidence is absent. The objective is to investigate the effect of adjunctive Lactobacillus casei on tuberculosis-drug-induced liver injury. METHODS AND RESULTS: A post hoc analysis is conducted for a previous randomized controlled trial. The trial is registered at the Chinese Clinical Trial Registry (No. ChiCTR-IOR-17013210). Four hundred twenty nine patients are allocated to receive standard tuberculosis therapy alone (control group), or together with 1 × 1010 colony-forming units (CFU) per day (low-dose group), or 2 × 1010 CFU per day of L. casei (high-dose group) during tuberculosis treatment. The L. casei supplementation significantly reduced the incidence of the abnormal increase of cholestasis-related liver indices including alkaline phosphatase (p = 0.024) and bilirubin (p = 0.013). Plasma lipopolysaccharide (p = 0.02), intestinal permeability biomarkers including zonula occludens-1 (p = 0.001) and intestinal fatty acid binding protein (p = 0.002) are significantly reduced. The gut microbiota composition is dramatically altered with a reduction of Bacteroidetes (p < 0.001) and a corresponding increase of Actinobacteria (p < 0.001) and Firmicutes (p = 0.003). CONCLUSIONS: L. casei supplementation is beneficial for suppressing abnormally elevated cholestasis-related liver indices during tuberculosis treatment, which may be related to its modification on blood lipopolysaccharide, intestinal barrier function, and gut microbiota.

Increased meat consumption is associated with reduced tuberculosis treatment failure rate: A cohort study.

BACKGROUND AND OBJECTIVES: Information regarding the relationship between dietary meat intake and tuberculosis treatment outcomes among patients with tuberculosis is still limited. The aim of the present study was to investigate the relationship between meat consumption and tuberculosis treatment outcomes in patients with pulmonary tuberculosis. METHODS AND STUDY DESIGN: A pulmonary tuberculosis cohort study including 2,261 patients with pulmonary tuberculosis was conducted in Linyi, Shandong Province, China from 2009 to 2013. Dietary data were collected using a semi-quantitative food frequency questionnaire. Treatment outcomes were assessed using a combination of sputum smear microscopy and chest computerized tomography. RESULTS: In a multiple adjusted model, the higher quartile of total meat (OR=0.59, 95% CI, 0.38-0.91) was associated with a decreased failure rate of pulmonary tuberculosis treatment. In addition, higher consumption of chicken (OR=0.62; 95% CI, 0.44-0.87) and pork (OR=0.54; 95% CI, 0.31-0.95) was associated with a lower failure rate of tuberculosis treatment. CONCLUSIONS: Increased dietary intake of total meat, pork, and chicken are associated with a decreased failure rate of pulmonary tuberculosis treatment. A higher dietary meat intake may be beneficial in pulmonary tuberculosis treatment.

Increased vegetable and fruit intake is associated with reduced failure rate of tuberculosis treatment: a hospital-based cohort study in China.

Increased intake of vegetables and fruits has been associated with reduced risk of tuberculosis infection. Vegetables and fruits exert immunoregulatory effects; however, it is not clear whether vegetables and fruits have an adjuvant treatment effect on tuberculosis. Between 2009 and 2013, a hospital-based cohort study was conducted in Linyi, Shandong Province, China. Treatment outcome was ascertained by sputum smear and chest computerised tomography, and dietary intake was assessed by a semi-quantitative FFQ. The dietary questionnaire was conducted at the end of month 2 of treatment initiation. Participants recalled their dietary intake of the previous 2 months. A total of 2309 patients were enrolled in this study. After 6 months of treatment, 2099 patients were successfully treated and 210 were uncured. In multivariate models, higher intake of total vegetables and fruits (OR 0·70; 95 % CI 0·49, 0·99), total vegetables (OR 0·68; 95 % CI 0·48, 0·97), dark-coloured vegetables (OR 0·61; 95 % CI 0·43, 0·86) and light-coloured vegetables (OR 0·67; 95 % CI 0·48, 0·95) were associated with reduced failure rate of tuberculosis treatment. No association was found between total fruit intake and reduced failure rate of tuberculosis treatment (OR 0·98; 95 % CI 0·70, 1·37). High intake of total vegetables and fruits, especially vegetables, is associated with lower risk of failure of tuberculosis treatment in pulmonary tuberculosis patients. The results provide important information for dietary guidelines during tuberculosis treatment.

Adjunctive vitamin A and D during pulmonary tuberculosis treatment: a randomized controlled trial with a 2 × 2 factorial design.

BACKGROUND AND OBJECTIVE: Vitamin A and D have immunoregulatory effects and may improve the response to pulmonary tuberculosis treatment. The interaction of vitamin A and D on pulmonary tuberculosis treatment has not been studied. The objective is to investigate the effects of adjunctive supplementation of vitamin A, D and their interaction on the outcome of pulmonary tuberculosis treatment, primarily time to sputum smear conversion. METHODS: We conducted a randomized controlled trial with a 2 × 2 factorial design in Qingdao, China. Eight hundred patients were enrolled to receive standard pulmonary tuberculosis therapy alone (control), or together with vitamin A (2000 IU d-1), or vitamin D (400 IU d-1) or a combination of vitamin A (2000 IU d-1) and D (400 IU d-1) during the intensive-phase of pulmonary tuberculosis treatment. RESULTS: 761 patients were included in the tuberculosis symptom analysis; 521 patients with positive baseline sputum smear results were included in the sputum smear analysis. The allocation to vitamin A or D did not significantly influence the time to sputum smear conversion [vitamin A: adjusted hazard ratio: 1.021, 95% CI: (0.821, 1.271); vitamin D: adjusted hazard ratio: 0.949, 95% CI: (0.760, 1.185)]. No significant interaction was observed between vitamin A and D supplementation (p = 0.660). Vitamin D supplementation significantly relieved the tuberculosis symptoms as indicated by decreased TBscore [mean difference: -0.2, 95% CI: (-0.4, 0)] in week 2 to 4. CONCLUSIONS: Adjunctive supplementation of vitamin A and/or D did not improve the time to smear conversion in pulmonary tuberculosis patients. However vitamin D supplementation significantly improved tuberculosis symptoms during the first month of pulmonary tuberculosis treatment.

Correction: Efficacy of proprietary Lactobacillus casei for anti-tuberculosis associated gastrointestinal adverse reactions in adult patients: a randomized, open-label, dose-response trial.

Correction for 'Efficacy of proprietary Lactobacillus casei for anti-tuberculosis associated gastrointestinal adverse reactions in adult patients: a randomized, open-label, dose-response trial' by Song Lin et al., Food Funct., 2020, 11, 370-377.

Long-Term Effects of Multi-Drug-Resistant Tuberculosis Treatment on Gut Microbiota and Its Health Consequences.

Gut microbiota dysbiosis has adverse health effects on human body. Multi-drug-resistant tuberculosis (MDR-TB) treatment uses a variety of antibiotics typically for more than 20 months, which may induce gut microbiota dysbiosis. The aim of this study is to investigate the long-term effects of MDR-TB treatment on human gut microbiota and its related health consequences. A total of 76 participants were recruited at a hospital in Linyi, China. The study included one active MDR-TB treatment group, one recovered group from MDR-TB and two treatment-naive tuberculosis groups as control. The two treatment-naïve tuberculosis groups were constructed to match the sex and the age of the active MDR-TB treatment and the recovered group, respectively. The fecal and blood samples were collected and analyzed for gut microbiota and metabolic parameters. An altered gut microbiota community and a loss of richness were observed during the MDR-TB treatment. Strikingly, 3-8 years after recovery and discontinuing the treatment, the gut microbiota still exhibited an altered taxonomic composition (p = 0.001) and a 16% decrease in richness (p = 0.018) compared to the gut microbiota before the treatment. The abundance of fifty-eight bacterial genera was significantly changed in the MDR-TB recovered group versus the untreated control group. Although there were persistent and pervasive gut microbiota alterations, no gastrointestinal symptom such as abdominal pain, diarrhea, nausea, flatulence, and constipation was observed in the recovered group. However, chronic disorders may be indicated by the elevated level of low-density lipoprotein cholesterol (LDLC) (p = 0.034) and total cholesterol (TC) (p = 0.017). These adverse lipid changes were associated with the altered gut bacterial taxa, including phylum Firmicutes and Verrucomicrobia and genera Adlercreutzia, Akkermansia, Butyricicoccus, Coprococcus, Clostridioides, Eubacterium, Erysipelatoclostridium, Fusicatenibacter, Klebsiella, Psychrobacter, and Streptococcus. Collectively, MDR-TB treatment induced a lasting gut microbiota dysbiosis, which was associated with unfavorable changes in lipid profile.

Efficacy of proprietary Lactobacillus casei for anti-tuberculosis associated gastrointestinal adverse reactions in adult patients: a randomized, open-label, dose-response trial.

Anti-tuberculosis (TB) drugs can induce a series of gastrointestinal adverse events, which can seriously affect patients' quality of life and may lead to treatment failure. Studies have shown that probiotics treatments can improve antibiotic-induced gastrointestinal symptoms. In this randomized, open-label, dose-response clinical trial, we investigated the preventive effects of Lactobacillus casei on anti-TB-induced gastrointestinal adverse events. In total, 429 adult patients who underwent intensive-phase anti-TB therapy were included and randomly assigned to consume one bottle of L. casei of per day (low-dose group, n = 142), two bottles of L. casei per day (high-dose group, n = 143), or no intervention (control group, n = 144) for 2 months. Each bottle of L. casei contained 10 billion colony-forming units of live L. casei. Patients' daily gastrointestinal symptoms were recorded during the intervention period. After 2 months of L. casei consumption, 397 patients had completed the intervention. Both the high and low dose L. casei groups (37.6% and 29.4%, respectively) had lower incidences of anti-TB-associated total gastrointestinal adverse events than the control group (50.0%). The high and low dose L. casei groups (3.5 d and 5.8 d, respectively) also had shorter duration anti-TB-associated adverse gastrointestinal symptoms than the control group (6.2 d). Regarding individual symptoms, the higher L. casei dose resulted in a lower incidence of vomiting and appetite loss. Similar dose-dependent protective effects of L. casei were observed regarding the duration of vomiting and appetite loss. These findings indicated that daily L. casei consumption prevented anti-TB-associated gastrointestinal adverse events. This trial was registered at the Chinese Clinical Trial Register (ChiCTR-IOR-17013210).

Poor Sleep Quality Is Associated with a Higher Risk of Pulmonary tuberculosis in Patients with a Type 2 Diabetes Mellitus Course for More than 5 Years.

A case-control study was conducted in Shandong from January to December 2017 to explore the relationship between sleep quality and the risk of active pulmonary tuberculosis (PTB). Seventy-nine patients with type 2 diabetes mellitus coincident with newly diagnosed pulmonary tuberculosis (DM-PTB) and 169 age, sex, and DM course frequency-matched controls (DM alone) were enrolled. Univariate and multivariable unconditional logistic regression analyses were conducted. We further conducted subgroup analyses to explore the relationship between sleep quality and PTB risk, including DM course (≤5 and ＞5 years), age, sex, and the presence of overweight or obesity (body mass index (BMI) ＞ 24 kg/m2). Multivariate logistic regression demonstrated that poor sleep quality had a borderline negative association with the odds of PTB (P ＝ 0.065). Subgroup multivariate analyses showed that poor sleep quality increased the risk of PTB to more than 3 times among patients with a DM course ＞ 5 years (odds ratio 3.31, 95% confidence interval: 1.08-10.13; P ＝ 0.036) after adjusting for potential confounding factors including residential area, educational level, BMI, history of contact with tuberculosis patients, smoking, alcohol consumption, physical exercise, immune status, and frequency of blood glucose monitoring. In conclusion, poor sleep quality is an independent risk factor of PTB among DM patients with a course of ＞ 5 years, which indicates significant epidemiological implications for PTB control.

Is low serum 25-hydroxyvitamin D a possible link between pulmonary tuberculosis and type 2 diabetes?

BACKGROUND AND OBJECTIVES: Although vitamin D is implicated in the generation of anti-microbial peptide cathelicidin, which plays a key role against pulmonary tuberculosis (PTB), and may have an inverse association with the risk of type 2 diabetes (DM), its role in the co-existence of these two diseases (PTB-DM) is still uncertain. This study explored the association of vitamin D status with prevalent PTB, PTB-DM and DM. METHODS AND STUDY DESIGN: We randomly selected 130 PTB patients, 90 PTB-DM, 91 DM and 134 controls. Serum 25(OH)D levels were determined. A structured questionnaire and anthropometric measurements were administered. RESULTS: Serum 25(OH)D levels in PTB and PTB-DM were 12.2±2.2 ng/mL and 12.9±2.5 ng/mL, respectively, which were lower than those in DM and control groups. Odds ratios of PTB and PTB-DM comparing extreme quartiles of 25(OH)D (lower than 8.6 ng/mL versus >=26.6 ng/mL) were 3.26 and 2.27, respectively. These associations remained after adjustment for possible risk factors [OR (95% CI)=4.73 (2.04-10.9) and 2.50 (1.04- 6.02), respectively]. A synergistic interaction was observed between low 25(OH)D and underweight in respect to prevalent PTB-DM [OR=24.6 vs 2.50 for lowest quartile of 25(OH) D and 4.59 for underweight]. CONCLUSIONS: Odds ratios of low serum 25(OH)D levels for PTB and PTB-DM were greater than 1.0, and were even much greater when combined with underweight. However, since the association of serum 25(OH)D levels with PTB was stronger than with PTB-DM, we could not draw the conclusion that vitamin D is a link between PTB and DM.

Association between body mass index and diabetes mellitus in tuberculosis patients in China: a community based cross-sectional study.

BACKGROUND: We planned to determine the association of body mass index (BMI) with diabetes mellitus (DM) and impaired fasting glucose (IFG) in Chinese pulmonary tuberculosis (PTB) patients. METHODS: 3,505 newly-diagnosed PTB patients registered in PTB clinics in Linyi of China between September 2010 and March 2013 were enrolled. DM and IFG were identified based on fasting plasma glucose levels. ROC analysis was used to predict the ability of screening of BMI for DM and IFG in PTB patients. RESULTS: Compared with 18.5-23.9 kg/m2, patients with DM and IFG had significantly increased trends when BMI ≥ 24.0 kg/m2, and aORs were 2.28 (95%CI 1.44-3.60) and 1.30 (95%CI 1.04-1.64), respectively. After adjustment for age, gender, and educational level, there was an increased odd in BMI ≥ 23.41 kg/m2 for IFG, and a decreased odd in BMI < 19.82 kg/m2 for DM (p < 0.05). The cut-offs of BMI for screening IFG and DM in PTB patients were 22.22 kg/m2 (AUC 0.56) and 22.34 kg/m2 (AUC 0.59). CONCLUSIONS: In PTB patients, BMI is significantly associated with IFG and DM. However, the predictive power of BMI was not sufficient, so it may only be a limited screening tool for DM and IFG among PTB patients in China.

Hyperglycemia is associated with increased risk of patient delay in pulmonary tuberculosis in rural areas.

BACKGROUND: Excessive time between the first presentation of symptoms of pulmonary tuberculosis (PTB) and diagnosis contributes to ongoing transmission and increased risk of infection in the community, as well as to increased disease severity and higher mortality. People with type 2 diabetes mellitus (T2DM) have a higher risk of developing PTB. However, the effect of T2DM on delayed diagnosis of PTB is not fully understood. This study investigated the effects of hyperglycemia (diabetes and prediabetes) and other factors on PTB patient delay in a rural area of China. METHODS: In the present community-based investigation, PTB patients aged ≥16 years newly diagnosed at county tuberculosis dispensaries were recruited consecutively between September 2011 and December 2013. Fasting blood glucose was determined in all subjects, and a structured questionnaire was used to collect basic information. RESULTS: Of the 2280 patients, 605 (26.5 %) had hyperglycemia. The median (interquartile range) time to seeking health care was 44 (59) days. Health care seeking was delayed in 1754 subjects, and hyperglycemia was independently associated with an increased probability (odds ratio 2.10; 95 % confidence interval 1.49-2.97) of patient delay in subjects aged ≥30 years. Other factors associated with patient delay were cough, night sweats, and lack of knowledge regarding typical tuberculosis symptoms. The onset of hemoptysis was negatively correlated with patient delay. CONCLUSIONS: Patient delay appears to be a serious problem in this rural area with a high prevalence of tuberculosis. Hyperglycemia is independently associated with an increased probability of patient delay, which, in turn, may result in more serious clinical manifestations.

Prevalence of type 2 diabetes among newly detected pulmonary tuberculosis patients in China: a community based cohort study.

BACKGROUND: Patients with type 2 diabetes (DM) have a higher risk of developing pulmonary tuberculosis (PTB); moreover, DM co-morbidity in PTB is associated with poor PTB treatment outcomes. Community based prevalence data on DM and prediabetes (pre-DM) among TB patients is lacking, particularly from the developing world. Therefore we conducted a prospective study to investigate the prevalence of DM and pre-DM and evaluated the risk factors for the presence of DM among newly detected PTB patients in rural areas of China. METHODS AND FINDINGS: In a prospective community based study carried out from 2010 to 2012, a representative sample of 6382 newly detected PTB patients from 7 TB clinics in Linyi were tested for DM. A population of 6674 non-TB controls from the same community was similarly tested as well. The prevalence of DM in TB patients (6.3%) was higher than that in non-TB controls (4.7%, p<0.05). PTB patients had a higher odds of DM than non-TB controls (adjusted OR 3.17, 95% CI 1.14-8.84). The prevalence of DM increased with age and was significantly higher in TB patients in the age categories above 30 years (p<0.05). Among TB patients, those with normal weight (BMI 18.5-23.9) had the lowest prevalence of DM (5.8%). Increasing age, family history of DM, positive sputum smear, cavity on chest X-ray and higher yearly income (≥10000 RMB yuan) were positively associated and frequent outdoor activity was negatively associated with DM in PTB patients. CONCLUSIONS: The prevalence of DM in PTB patients was higher than in non-TB controls with a 3 fold higher adjusted odds ratio of having DM. Given the increasing DM prevalence and still high burden of TB in China, this association may represent a new public health challenge concerning the prevention and treatment of both diseases.

Rationale and design of a randomized controlled trial of the effect of retinol and vitamin D supplementation on treatment in active pulmonary tuberculosis patients with diabetes.

BACKGROUND: The association between pulmonary tuberculosis (PTB) and diabetes mellitus (DM) has been previously attracted much attention. Diabetes alters immunity to tuberculosis, leading to more frequent treatment failure in TB patients with DM. Moreover, TB and DM often coincide with micronutrients deficiencies, such as retinol and vitamin D, which are especially important to immunity of the body and may influence pancreas ß-cell function. However, the effects of retinol and vitamin D supplementation in active TB patients with diabetes on treatment outcomes, immune and nutrition state are still uncertain. We are conducting a randomized controlled trial of vitamin A and/or D in active PTB patients with DM in a network of 4 TB treatment clinics to determine whether the supplementation could improve the outcome in the patients. METHODS/DESIGN: This is a 2×2 factorial trial. We plan to enroll 400 active PTB patients with DM, and randomize them to VA (2000 IU daily retinol); VD (400 IU daily cholecalciferol); VAD (2000 IU daily retinol plus 400 IU cholecalciferol) or control (placebo) group. Our primary outcome measure is the efficacy of anti-tuberculosis treatment and ameliorating of glucose metabolism, and the secondary outcome measure being immune and nutrition status of the subjects. Of the first 37 subjects enrolled: 8 have been randomized to VA, 10 to VD, 9 to VAD and 10 to control. To date, the sample is 97.3% Han Chinese and 91.9% female. The average fasting plasma glucose level is 12.19 mmol/L. DISCUSSION: This paper describes the design and rationale of a randomized clinical trial comparing VA and/or VD supplementation to active pulmonary TB patients with DM. Our trial will allow rigorous evaluation of the efficacy of the supplementation to active TB and DM therapy for improving clinical outcomes and immunological condition. This detailed description of trial methodology can serve as a template for the development of future treatment scheme for active TB patient with DM. TRIAL REGISTRATION: ChiCTR-TRC-12002546.