We excluded studies: amongst animals or children, if qualitative in design, case reports, case series, reviews, anonymous reports, editorials or author commentaries, with no appropriate control arm or comparator group, where TB patients with DM were not separated from those with other co-morbidities, of TB outcomes rather than the association, that did not report adjusted estimates of the TB–DM association, and duplicate reports. We contacted authors of potentially eligible studies to provide the adjusted estimate for the association, if the adjusted estimate was not included in the publication. Studies whose authors did not respond were excluded. The flow diagram of study selection is shown in Fig 1. First author (RHA) screened all titles and abstracts, reviewed full-text articles, and assessed their eligibility for inclusion. Figure 1: Flow diagram of study selection. Published studies were retrieved from the MEDLINE-PubMed and EMBASE databases. TB: tuberculosis; DM: diabetes mellitus. Data extraction and quality assessment Three authors (RHA, JAC, and LJA) designed the literature search terms and strategy. All potentially relevant full-text articles retrieved and reviewed to confirm eligibility. If eligible, data were extracted. All authors (RHA, FP, JAC, and LJA) contributed in assessing the eligibility of the included studies. The first author (RHA) extracted the data, which were re-extracted independently by at least one co-author (FP, JAC, or LJA). Discrepancies in data extraction were resolved by consensus or consultation with a third co-author. In addition to extracting baseline characteristics of included studies, we assessed methodological aspects, such as sampling strategy, characteristics of the study population, and TB and DM ascertainment. If a study
Moran-Mendoza et al (2010) [] Canada 1990–2000 General population in British Columbia Contacts of active TB cases recorded at the Division of TB control at the British Columbia Center for Diseases Control, excluding contacts of HIV infection cases or previous active TB cases DM ascertained from databases, but unclear which databases All TB by smear and/or culture positive for tubercle bacilli, histopathological diagnosis, or clinical and radiological diagnosis of active TB, with complete treatment response, when smears and cultures were negative 33,146 228 HR: 1.76 (0.54–5.75) 72 Age, sex, malignancy, corticosteroids, alcohol, malnutrition, closeness of TB contact, TST size in millimeter, intravenous drug use, ethnicity, SES, recent arrival from country with high TB prevalence, in prisons, nursing homes or homeless shelters, chest compatible with previous TB, & previous BCG vaccination. Adjustment was done with robust variance estimation Baker et al (2012) [] Taiwan August, 2004 General population Taiwanese adults aged ≥12 years interviewed during the Taiwan’s 2001 National Health Interview Survey (NHIS) Treated DM ascertained by ≥2 outpatient ICD–9–CM codes for DM, ≥1 inpatient ICD–9–CM code for DM, or prescription of medications for ≥28 days during the study period or ≥2 prescriptions All TB ascertained if all of the following criteria reported in NHIS database: ≥1 medical visit during the follow-up period with an ICD–9–CM code for TB (codes 010–018); a prescription for ≥2 anti-TB medications for >28 days during the study period; and no finding of a misdiagnosis of TB during the study period on the basis of later diagnosis of non-TB mycobacterial infection, lung cancer, or TB infection without evidence of disease 17,715 57 HR: 2.60 (1.34–5.03) 73 Age, sex, income, employment, alcohol use, education, BMI, living in a crowded home, receipt of government subsidy, residence in an indigenous community, hypertension, heart disease, & lung disease 2001–
Wu et al (2011) [] Taiwan January, 2007 General population New onset cancer patients and patients recorded in the Taiwan’s’ National Health Insurance Database in 2005, matched by sex and age DM ascertained by ICD–9–250 All TB ascertained by with prescription history of treatment with isoniazid 82,435 694 HR: 1.38 (1.17–1.62) 64.89 in 1998 75 in 2002 67 in 2003 74 in 2004 72.5 in 2005 67 in 2006 63 in 20074 Age, sex, chronic renal failure, autoimmune diseases, COPD, aerodigestive tract and lung cancers, haematological cancers, & other major/less common cancers Chen et al (2006) [] Taiwan January, 2003 Hospitals Renal transplant recipients in Taichung DM ascertained from medical records All TB ascertained either by positive culture, presence of caseating or non–caseating granuloma in biopsy specimens taken from involved tissue and responsive to treatment, or typical chest X–ray finding or clinical presentation consistent with TB, without microbiological or pathological confirmation but with favorable response to anti-TB treatment 756 29 RRs: 3.07 (1.14–8.26) 66.67 Age, sex, dialysis duration, hepatitis B virus infection, hepatitis C virus infection, graft rejection >3, & medications Adjusted effect estimate reported in the previous review[] Rungruanghiranya et al (2008) [] Thailand January, 2007 Nationwide Renal transplant recipients DM ascertained from case medical records All TB ascertained by one or more of: AFB in body fluid smears, TB-polymerase chain reaction, and/or growth in various culture specimens; histopathology examination of tissue specimens showing either AFB or granulomatous inflammation; response to TB treatment in patients with typical radiographic findings consistent with TB, or those who had fever of unknown origin despite negative results of extensive investigations 233 9 OR: 3.59 (0.74–17.35) 142 in 2005 Age & sex5 010–018 December,
diagnosed with non-TB mycobacterial infection Leegaard et al (2011) [] Denmark January, 2008 Northern Danish population Cases: first time hospital contact with principal diagnosis of TB obtained from DNRP who lived in Northern Denmark for ≥6 months since the TB diagnosis date Controls: TB-free individuals from Danish civilian registration system DM ascertained by in- or outpatient hospital contact involving diabetes, any use of oral anti-diabetes drugs or insulin, at least one visit to a chiropodist for diabetes 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. Patients under 30 on therapy = Type 1DM, rest Type 2DM. HbA1c where available for a subset of controls and cases. Type 1 DM Type 2 DM All TB ascertained by ICD–8: 010–019; ICD–10: A15–A19 codes. A subset microbiologically confirmed TB 2,950 14,274 1.18 (0.96–1.45) 2.59 (0.44–15.29) 1.17 (0.95–1.44) 7 Matched by: age (±5 years), sex, country of origin, & place & length of residence in Denmark (±1 year) Adjusted for: age, sex, country of origin, place & length of residence in Denmark, comorbidities (myocardial infarction, congestive heart failure, peripheral vascular disease, CVD, dementia, COPD, connective tissue disease , ulcer disease, mild liver disease, hemiplegia, moderate to severe renal disease, any tumor, leukemia, lymphoma, metastatic solid tumor, & HIV/AIDS), alcoholism-related disorders, marital status, number of children <15 years, & degree of urbanization
Jurcev-Savicevic et al (2013) [] Croatia 2006–2008 Seven Croatian counties Cases: TB-patients aged ≥15 years Controls: TB-free individuals from database of general practitioners in each TB-case county who had not developed TB in a two-month period DM ascertainment by self-report Pulmonary TB ascertained by bacterial positive culture among cases 300 300 2.38 (1.05–5.38) 23 Matched by: age (±2 years), sex, & county of residence that had no history of TB from the database of general practitioners Adjusted for: age, sex, BMI, country of birth of parents, education, household equipment, employment, smoking status, contact with TB, & malignant disease Jick et al (2006) [] UK 1990–2001 General population Cases: first–time TB–patients obtained from General Practice Research Database Controls: TB–free individuals from same database DM ascertained by presence of anti-DM medication prior to TB index date All TB ascertained by prescription of at least 3 anti-TB medications for at least 6 months 497 1,966 3.80 (2.30–6.10) 3 Matched by: age, sex, geography, index date, & medical history Adjusted for: age, sex, index date, amount of computerized medical history, glucocorticoid use, smoking, BMI, pulmonary disease, & use of / immunosuppressive agents Pablos-Mendez et al (1997) [] USA 1991 Civilian hospitals in California Cases: TB–patients Controls: TB–free patients with primary discharge diagnosis of deep venous thrombosis of the legs, pulmonary embolism, or acute appendicitis DM ascertained from medical charts coded as ICD–9 250.0–250.9 Type 1 DM Type 2 DM All TB coded as ICD–9 010 to 018 5,290 37,366 1.53 (0.81–2.90) 1.40 (0.83–2.35) 1.02 (0.63–1.66) 17.32 Matched by: age & race Adjusted for: aORs for age, sex, poor education, median income, health insurance, conditions, chronic renal insufficiency, alcohol-related conditions, & drug use were pooled
using model5 Perez et al (2006) [] USA 1999–2001 15 Texas/Mexico border counties Cases: TB-patients aged ≥15 years from Texas hospitals discharge database Controls: TB-free patients aged ≥15 years with deep venous thrombosis, pulmonary embolism, or acute appendicitis from same database. Excluding HIV cases. DM ascertained from medical chart coded as ICD–9: 250.0 –250.9 All TB coded as ICD–9 code 010–018. TB codes were sought in the admitting diagnosis, principal diagnosis, and eight other variables with diagnosis codes 3,847 66,714 1.75 (1.32–2.33) counties: 13.1 Non-Mexico borders counties: 6.6 Region-specific aORs for age, sex, race/ethnicity, insurance type/status, any type of cancer, chronic renal failure, nutrition deficit, income, & education were pooled using random–effects model5 Corris et al (2012) [] USA 1976–1980 General population Cases: TB–patients aged 20–74 years Controls: TB–free individuals aged years Cases & controls were a sample from the second National Health and Nutrition Examination Survey included weighted civilian US population DM was ascertained by self-report to questions “Do you have diabetes or sugar diabetes?, "Have you ever been told by a doctor that you have borderline diabetes?" and/or a 75g OGTT test at current WHO cut points (OGTT takes precedence) All TB ascertained by ever received diagnosis of TB from a doctor regardless of whether they still had it 166 15,191 2.31 (1.36–3.93) 11 in 19824 Adjusted for: age, race, poverty index, BMI, household contact with TB, & cigarette smoking status Buskin et al (1994) [] USA 1988–1990 Seattle/King county TB clinic Cases: TB–patients, residents of King County aged >17 years seeking care at a TB clinic in Washington Controls: active residents of King County aged >17 years seeking DM ascertained by history of DM taken from the questionnaire 1.7 months after the date of TB onset All TB ascertained by CDC, 1990 criteria that emphasize laboratory confirmation of Mycobacterium tuberculosis and other specified criteria[] 151 545 1.70 (0.70–4.30) 9 Adjusted for: age
without symptoms of TB) Coker et al (2006) [] Russia January, 2003 Residents in the city of Samara Cases: newly diagnosed adult at any of city’s specialist TB clinics and recruited to a WHO DOT program Controls: TB–free general residents of the Samara city Method of DM ascertained was an unclear Pulmonary TB ascertained by positive bacterial culture 334 334 7.83 (2.37–25.89) 1182 Matched by: age & sex Adjusted for: age, sex, relative with TB, alcohol, drinking raw milk, assets, number of cohabitating person, employment, smoking, financial security, illicit drugs, & imprisonment Faurholt-Jepsen et al (2011) [] Tanzania April, 2009 Four major health facilities in Mwanza city Cases: TB–patients aged ≥15 years, excluding pregnant or lactating women, patients terminally ill from TB or HIV, patients suffering from other severe diseases, & non–residents of Mwanza City Controls: TB–free aged ≥15 years, with no history of TB in the household members and no evidence of active TB (cough, intermittent fevers, excessive night sweating in the past two weeks, and unexplained weight loss in the past month) DM ascertained by either FBG >6mmol/L or OGTT >11mmol/L according to WHO guidelines, for both cases and controls Pulmonary TB ascertained by initial diagnosis with sputum positive microscopy based on three sputum samples with an additional early morning sputum sample was collected for Mycobacterium tuberculosis culture, for both cases and controls 803 350 2.13 (1.37–3.31) 504 in 2006 452 in 20092 Matched by: residence, sex, age (± 5 years), not pregnant or lactating, not terminally ill from TB or HIV, not suffering from other diseases, & resident of Mwanaza city Adjusted for: aORs for age, sex, religion, marital status, & occupation were pooled using random–effects model5 specific
Wu et al (2007) [] Taiwan January, 2004 Chang Gung Memorial Hospital, Keelung Cases: TB–patients with lower respiratory tract infection or who had been in contact with TB patients Controls: non–TB pneumonia patients who did not meet the criteria for TB DM ascertained from medical records Pulmonary TB ascertained by positive sputum culture for Mycobacterium tuberculosis 264 438 3.43 (2.16–5.46) 75 in 2002 67 in 2003 74 in 20042 Adjusted for: age, sex, pneumoconiosis, bronchiectasis, liver cirrhosis, haemodialysis, & lung cancer Rosenman and Hall, (1996) [] USA January, 1985– May, 1987 New Jersey Department of Health Cases: male aged ≥35 years who speak English, excluding HIV positive and/or foreign born cases Controls: TB-free individuals registered at the New Jersey Department of Health DM ascertained by All TB ascertained by positive mycobacterium tuberculosis culture, or who had a physician diagnosis of pulmonary TB with multidrug medication 148 290 1.16 (0.58–2.32) 9.5 Matched by: age (±5 years), gender, & race Adjusted for: age, sex, & race Cross-sectional Goldhaber-Fiebert et al (2011) [] WHO survey 2002–2003 46 countries General population DM ascertained by based on positive response to the question "Have you ever been diagnosed with diabetes (high blood glucose)?" All TB ascertained by self-reported symptoms of active TB, based on positive response to two questions "Over the last 12 months, have you had blood in your phlegm or have you coughed blood?" & "Over the last 12 months, have you experienced cough lasting over 3 weeks?" 124,545 1,744 1.81 (1.37–2.39) - Age, sex, BMI, schooling in years, smoking & length of being daily smoker, urban and rural residence, at least 1 drink per day, number of household members, number of individuals per room, & SES based on different household’s assets