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Table 2 Summary characteristics of 17 observational studies in the review

From: The association of glycemic level and prevalence of tuberculosis: a meta-analysis

Study Outcomes Inclusion of diabetic patients Definition of TB Parameters Estimated OR/RR/HR (95% CI) Adjustment
Cohort study
Golub 2019 Incident TB, recurrent TB DM was identified using International Classification of Diseases, Tenth Revision (ICD-10) codes E10–E10x and E14–E14x; defined using the following criteria: 1) FSG at baseline, 2) out-patient treatment for DM (at least three visits for DM care during a 365-day window) or 3) at least one hospitalization due to DM. TB was identified using ICD-10 codes A15–A19.10; incident TB was defined by any of the following during follow-up: 1) hospitalization due to TB, 2) two or more out-patient visits for TB, or 3) receipt of at least three anti-TB medications. Prevalent TB was defined as meeting the criteria listed above either at baseline or between 1997 and 2000. Recurrent TB was considered to have occurred if the criterion for incident TB was met in a participant with previous or prevalent TB. FSG (mean, < 5.0, 5.0–5.6, 5.6–7.0, 7.0–7.8, ≥7.8 mmol/L) Adjusted HR: Incidence TB (Ref: FSG < 5.0 mmol/L): Male: FSG (mmol/l): 5.0–< 5.6: 0.94 (0.90–0.99); 5.6–< 7.0: 1.05 (1.00–1.11); 7.0–< 7.8: 1.50 (1.33–1.69); ≥7.8: 1.87 (1.74–2.02); Female: FSG (mmol/l): 5.0–< 5.6: 0.97 (0.90–1.03); 5.6–< 7.0: 0.97 (0.89–1.04); 7.0–< 7.8: 1.14 (0.92–1.41); ≥7.8: 1.41 (1.23–1.61); Recurrence TB (Ref: FSG < 5.0 mmol/L): Male: FSG (mmol/l): 5.0–< 5.6: 1.04 (0.97–1.12); 5.6–< 7.0: 1.11 (1.03–1.20); 7.0–< 7.8: 1.17 (0.94–1.45); ≥7.8: 2.01 (1.79–2.26); Female: FSG (mmol/l): 5.0–< 5.6: 1.04 (0.91–1.19); 5.6–< 7.0: 1.12 (0.95–1.31); 7.0–< 7.8: 1.07 (0.64–1.79); ≥7.8: 1.28 (0.91–1.80) Adjusted for age, (age)2, alcohol consumption (0 g/day, < 50 g/day and ≥ 50 g/day), smoking status, BMI, (BMI)2, past history of cancer, past history of chronic kidney disease, medical insurance premium and (medical insurance premium)2.
Lee 2016 Active TB DM status and glycemic control were defined using information from the screening service (FPG) and the national health insurance database. DM was defined by the prescription of a hypoglycemic drug for ≥28 d within 2 y before the date of screening or FPG ≥126 mg/dl at screening. TB were defined as ICD-9-CM code 010–018 in the patient’s medical record plus prescription of anti-TB treatment for ≥90 d (including inpatient and outpatient services). FPG, mg/dl (≤130, > 130) Adjusted HR (Ref: No DM): FPG ≤130 mg/dl: 0.69 (0.35–1.36); FPG > 130 mg/dl: 2.21 (1.63–2.99) Adjusted for age, sex, smoking status, alcohol use, betel nut use, education level, marital status, BMI, malignancy, pneumoconiosis, steroid use, ESRD, and frequency of outpatient visits.
Leung 2008 Active TB Patients were recruited who enrolled at the 18 Elderly Health Service centers in Hongkong. DM was diagnosed, mainly by a FPG level of 7.0 mmol/liter or higher, together with confirmatory symptoms and/or blood/plasma glucose determinations. The diagnosis of and clinical information on all identified TB cases were verified by reviewing medical records retrieved from chest clinics and other relevant sources, as well as the public health records of the TB and Chest Service. An active case of TB was defined as disease proven by isolation of Mycobacterium TB or, in the absence of bacteriologic confirmation, disease diagnose don clinical, radiologic, and/or histologic grounds together with an appropriate response to anti-TB treatment. HbA1c (< 7%, ≥7%) Crude RR (Ref: no DM): HbA1c < 7%: 0.64 (0.35, 1.16); HbA1c ≥ 7%: 1.97 (1.51, 2.57)  
Qiu 2017 TB The data used were from Shanghai community-based DM management system (SCDMS), a DM register operated by the Shanghai Municipal Centers for Disease Control and Prevention (Shanghai-CDC). The diagnosis of DM must be verified by physicians in Community Health Centers (CHCs) using 1999 World Health Organization (WHO) criteria. All TB diagnoses were confirmed by laboratory-based diagnostic tests using the China National TB Diagnostic Guidelines, including acid-fast bacilli (AFB) smear and culture test, purified protein derivative (PPD) skin test and serological test for Mycobacterium TB infection (Mtb). Initial fasting glucose (mmol/L); Fasting glucose change (estimated by subtracting the initial values from the means of follow-up) (mmol/L) Adjusted HR: initial fasting glucose (mmol/L): men: 1.21 (1.15,1.27); women: 1.27 (1.18,1.37); fasting glucose change (mmol/L): men: 1.17 (1.11,1.24); women: 1.27 (1.16,1.40) < 0.01 Not found
Case-control study
Khalil 2016 Active TB Patients were considered to be diabetic if they had a previous history of DM and were receiving antidiabetic therapy or were later found to have fasting plasma glucose ≥7.0 mmol/l (126 mg/dl). Or with a glucose tolerance test, two hours after the oral dose of plasma glucose 11.1 mmol/l (200 mg dl). Glycated hemoglobin (HbA1c) of greater than 6.5% is another method of diagnosis, also random blood sugar of greater than ≥11.1 mmol/l (200 mg/dl) in association with typical symptoms. Patients were considered TB if at least two initial sputum smears positive for AFB (acid fast bacilli); or one sputum examination positive for AFB & radiographic abnormalities consistent with active pulmonary TB; or one sputum positive for AFB & culture positive for M. TB, and considered a new case if patient has never had treatment for TB or who has taken anti-TB drugs for less than one month. Fasting blood sugar (mean); post prandial blood sugar (mean), HbA1c (mean)   
Leal 2019 TB All the diabetics seen at the 30 municipal health units of Vitória, ES, Brazil were recruited. Patients who were had a history of TB diagnosis and were notified at the Sistema de Informação de Agravos de Notificação (SINAN – Information System for Notifiable Diseases). FBG (mean), PPG (mean), HbA1c (mean)   
Leegaard 2011 Active TB DM was defined as previous in- or outpatient hospital contact involving DM, any use of oral anti-DM drugs or insulin, at least one visit to a chiropodist for DM foot care, at least five glucose-related services in general practice in 1 year, or at least two glucose-related services each year during 5 subsequent years. Cases of active TB either had Mycobacterium tuberculosis complex (except M. bovis Bacillus Calmette-Guérin) isolated from a clinical specimen, or had M. tuberculosis DNA detected by PCR analysis, acid-fast bacilli demonstrated by direct microscopy, granuloma detected by histology, or had signs, symptoms, and/or radiological findings consistent with active TB in any site. HbA1c, % (< 7.0, 7.0–7.9, ≥8.0) Adjusted OR (Ref: No DM): < 7.0: 0.91 (0.51–1.63); 7.0–7.9: 1.05 (0.41–2.66); ≥8.0: 1.19 (0.61–2.30) Adjusted for level of comorbidity, alcoholism-related disorders, marital status, number of children under the age of 15, and degree of urbanization.
Marupuru 2017 TB Patients were recruited from a tertiary care hospital in South-India (Kasturba Hospital (KH), Manipal). Data were obtained from were obtained from the Medical Records Department of the hospital. Subjects were identified based on ICD-10 coding for disease classification (TB: A15–A19). FBS, mg/dl (median, < 70, 70–100, > 100); HbA1c, %, (median, < 7.0, 7.0–8.0, > 8.0) Crude RR (Ref: HbA1c ≥7%): HbA1c < 7%: 0.52 (0.29, 0.93)  
Widjaja 2018 TB Patients were recruited from MurniTeguh Memorial Hospitals in Medan, Indonesia. Only patients diagnosed with diabetes and who gave signed informed consent were admitted to the study. Blood glucose (mean), HbA1c (mean)   
Cross–sectional study
Almeida-Junior 2016 TB Patients were recruited from the Instituto Brasileiro para a Investigação da Tuberculose (IBIT, Brazilian Institute for TB investigation). The presence of DM was defined in accordance with American DM Association (ADA) guidelines as 2-h glucose ≥11.1 mmol/L, HbA1c ≥ 6.5% or fasting plasma glucose ≥7.0 mmol/L. Diagnosis of TB at IBIT follows the guidelines of the Brazilian Society of Pulmonology and Tisiology, which is similar to WHO recommendations. HbA1c, % (< 7, ≥7%); fasting glucose, OGTT Adjusted OR: HbA1c: 1.40 (1.25–1.56); fasting glucose: 1.01 (1.004–1.01); OGTT: 1.01 (1.002–1.014) (for increases of 1 unit in plasma values of HbA1c, fasting glucose or OGTT glycaemia (after log10 transformation)) Adjusted for age, gender and BMI
Berkowitz 2018 Active TB Participants were recruited from a DM clinic, where their diagnosis had been previously made. TB screening and diagnoses were conducted using the national TB management guidelines. Participants were classified as having subclinical TB if diagnosed with active TB but with an absence of any clinical symptoms. An active TB case was defined as persons who tested positive for M. tuberculosis by either GeneXpert, smear microscopy, or TB culture in the presence or absence of clinical symptoms. HbA1c, % (< 7, > 7%); FPG Crude RR (Ref: HbA1c < 7%): HbA1c ≥ 7%: 3.07 (0.37–22.60)  
Chan 2019 Active TB Patients were recruited if he/she registered in the National DM Registry. Three sputum samples for AFB stain were obtained from each subject who presented with cough. Sputum smear positive PTB was defined as having at least one sputum sample positive for AFB, a CXR result consistent with typical PTB (consolidation/cavitations of an upper lung zone) and/or having symptoms of PTB (cough for > 2 weeks, weight loss, night sweats or fever for > 4 weeks). Subjects with sputum smear negative for AFB or having other symptoms of PTB with an abnormal CXR with typical findings of active PTB were referred to a chest physician to exclude smear negative PTB. Chest physicians evaluated the subjects with either a CT scan of the thorax and/ or bronchoscopy with washings for AFB. Subjects were then classified as being either sputum smear positive or smear negative PTB. HbA1c (mean) Crude OR: 1.30 (95% CI: 1.01–1.76)  
Hensel 2016 Latent TB Patients were refugees seen at a health clinic in Atlanta, GA, USA. Patients with HbA1c < 6.5% with a previous diagnosis of DM indicated in their medical chart were also defined as DM. Patients were considered to have LTBI if the QFT results were positive and chest radiographs were negative. HbA1c, % (median); random blood glucose, mg/dl (median) Crude OR (95%CI): DM status (Ref: No DM): Pre-DM: 1.83 (1.30–2.58); DM: 2.19 (1.22–3.94); Adjusted OR (95%CI): DM status (Ref: No DM): Pre-DM: 1.65 (1.13–2.39); DM: 2.27 (1.15–4.48) Adjusted for age, sex, BMI, TB incidence in country of origin, smoking status, and vitamin D level.
Kumpatla 2013 TB Patients attending the hospital and suspected of having DM are screened using the 2 h 75 g oral glucose tolerance test. The diagnosis of DM is based on previous DM history or on the WHO’s criteria for the classification of glucose intolerance. patients with cough for 2 weeks or any suspicion of active pulmonary TB (PTB) or extra-pulmonary TB were categorized as having presumptive TB and were further investigated to confirm the disease. Two same-day sputum specimens from presumptive TB patients were collected in the DM clinic and transported to the government-run microscopy center for sputum smear microscopy by Ziehl-Neelsen staining. Patients with negative sputum smears or extra-pulmonary TB suspects underwent appropriate investigations such as chest radiography to confirm TB. fasting and postprandial glucose, mg/dl (mean); HbA1c, % (< 7%, 7–8.9%, ≥9%)   
Martinez-Aguilar 2015 Latent TB Subjects with a medical history of DM receiving hypoglycemic drugs and/or insulin treatment at IMSS primary healthcare services of Durango City, Durango, Guadalupe and Zacatecas, Zacatecas (cities located in the central region of Northern Mexico) were randomly selected and recruited. Subjects with a positive TST but with no evidence of active TB were considered as having LTBI. Fasting glucose, mg/dL (median); HbA1c, % (median, ≤7, > 7%) Adjusted OR (Ref: HbA1c ≤7%): HbA1c > 7%: 2.52 (1.10–8.25) Adjusted for age and gender.
Sanchez-Jimenez 2018 Active TB Patients were recruited from the National Institute of Respiratory Diseases (INER) “Ismael Cosío Villegas”; DM were confirmed by the clinical history, glucose tolerance test, fasting glucose levels ≥126 mg/dl, and by HbA1c ≥ 6.5%. Pulmonary TB diagnosis was based on clinical history, physical examination, chest X-rays, and positive Ziehl-Neelsen test in sputum. The fasting glucose (median), HbA1c (median)   
Webb 2009 Active TB All children and adolescents (0–21 years) with documented type I DM who were routinely assessed during the study period at the two hospitals were eligible. Type I DM was considered present if a diagnosis was previously made by a pediatric endocrinologist. A diagnosis of probable pulmonary TB disease was made when all three of the following criteria were met: 1) CXR changes consistent with TB; 2) clinical features of TB disease: respiratory symptoms (cough > 2 weeks, hemoptysis, dyspnea) and constitutional symptoms (fever, night sweat, fatigue or weight loss); and 3) TST 10 mm. HbA1c (mean) Crude hazard ratio (95%CI): 1.39 (1.18–1.63) for per unit increase in HbA1c at diagnosis with TB.  
  1. Abbreviation: DM: Diabetes mellitus, FBG: Fasting blood glucose, FPG: Fasting plasma glucose, HbA1c: Glycated hemoglobin A1c, HR: Hazard ratio, LTBI: Latent tuberculosis infection, OGTT: Oral glucose tolerance test, OR: Odds ratio, PPG: Post prandial blood glucose, TB: Tuberculosis, RR: Relative risk