The burgeoning epidemic of diabetes mellitus (DM) is one of the major global health challenges. We systematically reviewed the published literature to provide a summary estimate of the association between DM and active tuberculosis (TB). We searched Medline and EMBASE databases for studies reporting adjusted estimates on the TB–DM association published before December 22, 2015, with no restrictions on region and language. In the meta-analysis, adjusted estimates were pooled using a DerSimonian-Laird random-effects model, according to study design. Risk of bias assessment and sensitivity analyses were conducted. 44 eligible studies were included, which consisted of 58,468,404 subjects from 16 countries. Compared with non-DM patients, DM patients had 3.59–fold (95% confidence interval (CI) 2.25–5.73), 1.55–fold (95% CI 1.39–1.72), and 2.09–fold (95% CI 1.71–2.55) increased risk of active TB in four prospective, 16 retrospective, and 17 case-control studies, respectively. Country income level (3.16–fold in low/middle–vs. 1.73–fold in high–income countries), background TB incidence (2.05–fold in countries with >50 vs. 1.89–fold in countries with ≤50 TB cases per 100,000 person-year), and geographical region (2.44–fold in Asia vs. 1.71–fold in Europe and 1.73–fold in USA/Canada) affected appreciably the estimated association, but potential risk of bias, type of population (general versus clinical), and potential for duplicate data, did not. Microbiological ascertainment for TB (3.03–fold) and/or blood testing for DM (3.10–fold), as well as uncontrolled DM (3.30–fold), resulted in stronger estimated association. DM is associated with a two- to four-fold increased risk of active TB. The association was stronger when ascertainment was based on biological testing rather than medical records or self-report. The burgeoning DM epidemic could impact upon the achievements of the WHO “End TB Strategy” for reducing TB incidence.

Diabetes triples the risk for active tuberculosis, thus the increasing burden of type 2 diabetes will help to sustain the present tuberculosis epidemic. Recommendations have been made for bidirectional screening, but evidence is scarce about the performance of specific tuberculosis tests in individuals with diabetes, specific diabetes tests in patients with tuberculosis, and screening and preventive therapy for latent tuberculosis infections in individuals with diabetes. Clinical management of patients with both diseases can be difficult. Tuberculosis patients with diabetes have a lower concentration of tuberculosis drugs and a higher risk of drug toxicity than tuberculosis patients without diabetes. Good glycaemic control, which reduces long-term diabetes complications and could also improve tuberculosis treatment outcomes, is hampered by chronic inflammation, drug-drug interactions, suboptimum adherence to drug treatments, and other factors. Besides drug treatments for tuberculosis and diabetes, other interventions, such as education, intensive monitoring, and lifestyle interventions, might be needed, especially for patients with newly diagnosed diabetes or those who need insulin. From a health systems point of view, delivery of optimum care and integration of services for tuberculosis and diabetes is a huge challenge in many countries. Experience from the combined tuberculosis and HIV/AIDS epidemic could serve as an example, but more studies are needed that include economic assessments of recommended screening and systems to manage concurrent tuberculosis and diabetes.

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BackgroundDiabetes mellitus (DM) increases active tuberculosis (TB) risk and worsens TB outcomes, jeopardizing TB control especially in TB-endemic countries with rising DM prevalence rates. We assessed DM status and clinical correlates in TB patients across settings in Indonesia, Peru, Romania, and South Africa.MethodsAge-adjusted DM prevalence was estimated using laboratory glycated hemoglobin (HbA1c) or fasting plasma glucose in TB patients. Detailed and standardized sociodemographic, anthropometric, and clinical measurements were made. Characteristics of TB patients with or without DM were compared using multilevel mixed-effect regression models with robust standard errors.ResultsOf 2185 TB patients (median age 36.6 years, 61.2% male, 3.8% human immunodeficiency virus–infected), 12.5% (267/2128) had DM, one third of whom were newly diagnosed. Age-standardized DM prevalence ranged from 10.9% (South Africa) to 19.7% (Indonesia). Median HbA1c in TB–DM patients ranged from 7.4% (Romania) to 11.3% (Indonesia). Compared to those without DM, TB–DM patients were older and had a higher body mass index (BMI) (P value < .05). Compared to those with newly diagnosed DM, TB patients with diagnosed DM had higher BMI and HbA1c, less severe TB, and more frequent comorbidities, DM complications, and hypertension (P value < .05).ConclusionsWe show that DM prevalence and clinical characteristics of TB–DM vary across settings. Diabetes is primarily known but untreated, hyperglycemia is often severe, and many patients with TB–DM have significant cardiovascular disease risk and severe TB. This underlines the need to improve strategies for better clinical management of combined TB and DM.

ObjectiveTo evaluate the performance of diagnostic tools for diabetes mellitus, including laboratory methods and clinical risk scores, in newly-diagnosed pulmonary tuberculosis patients from four middle-income countries.MethodsIn a multicentre, prospective study, we recruited 2185 patients with pulmonary tuberculosis from sites in Indonesia, Peru, Romania and South Africa from January 2014 to September 2016. Using laboratory-measured glycated haemoglobin (HbA1c) as the gold standard, we measured the diagnostic accuracy of random plasma glucose, point-of-care HbA1c, fasting blood glucose, urine dipstick, published and newly derived diabetes mellitus risk scores and anthropometric measurements. We also analysed combinations of tests, including a two-step test using point-of-care HbA1cwhen initial random plasma glucose was ≥ 6.1 mmol/L.FindingsThe overall crude prevalence of diabetes mellitus among newly diagnosed tuberculosis patients was 283/2185 (13.0%; 95% confidence interval, CI: 11.6–14.4). The marker with the best diagnostic accuracy was point-of-care HbA1c (area under receiver operating characteristic curve: 0.81; 95% CI: 0.75–0.86). A risk score derived using age, point-of-care HbA1c and random plasma glucose had the best overall diagnostic accuracy (area under curve: 0.85; 95% CI: 0.81–0.90). There was substantial heterogeneity between sites for all markers, but the two-step combination test performed well in Indonesia and Peru.ConclusionRandom plasma glucose followed by point-of-care HbA1c testing can accurately diagnose diabetes in tuberculosis patients, particularly those with substantial hyperglycaemia, while reducing the need for more expensive point-of-care HbA1c testing. Risk scores with or without biochemical data may be useful but require validation.

It is unlikely that adjunctive corticosteroid treatment provides major benefits for people with pulmonary tuberculosis. Short term clinical benefits found did not appear to be maintained in the long term. However, evidence available to date is of low quality. In order to evaluate whether adjunctive corticosteroids reduce mortality, or accelerate clinical or microbiological recovery in people with pulmonary tuberculosis further large randomized control trials sufficiently powered to detect changes in such outcomes are needed.

DM patients in government clinics in four LMIC with considerable growth of DM have insufficient glycaemic control, frequent macrovascular and other complications, and insufficient preventive measures for cardiovascular disease. These findings underline the need to identify treatment barriers and secure optimal DM care in such settings.

on behalf of the TANDEM consortium (members listed in full in submitted excel 9 spreadsheet) 10 11 1. Population Summary 48Background 49 Diabetes (DM) is common among tuberculosis (TB) patients and often undiagnosed or poorly 50 controlled. We compared point of care (POC) with laboratory glycated haemoglobin (HbA1c) tests 51 among newly diagnosed TB patients to assess POC test accuracy, safety, and acceptability in settings 52where immediate access to DM services may be difficult. 53 Methods 54We measured POC and accredited laboratory HbA1c (HPLC method) in 1942 TB patients aged over 18, 55 recruited from Peru, Romania, Indonesia, and South Africa. We calculated overall agreement and 56 individual variation (mean ± 2 standard deviations); stratified by country, age, sex, body mass index 57 (BMI), HbA1c level and comorbidities (anaemia, human immunodeficiency virus (HIV)). We used an 58 error grid approach to identify disagreement that could raise significant concerns. 59 Results 60Overall mean POC HbA1c values were modestly greater than laboratory HbA1c by 0.14% units (95% 61 confidence intervals 0.11 to 0.18), but there was a substantial discrepancy for those with severe 62 anaemia (1.07% HbA1c, 95%CI 0.67 to 1.46). For 89.6% of 1942 patients, both values indicated the 63 same DM status (no DM; HbA1c <6.5%) or had acceptable deviation (relative difference <6%). 64 Individual agreement was variable, with POC values up to 1.84% units higher or 1.56% lower. For a 65 minority, use of POC HbA1c alone could result in error leading to potential over-treatment (n=40, 2.1%) 66 or under treatment (n=1, 0.05%). The remainder had moderate disagreement, less likely to influence 67 clinical decisions. 68 Conclusion 69 POC HbA1c is pragmatic and sufficiently accurate to screen for hyperglycaemia and DM risk among TB 70 patients. 71 72 73 74 POC HbA1c (analysed using Hemocue® HbA1c 501 Analyser)[34] was collected during the participants' 131 clinic visits, and within 72 hours after TB diagnosis. In Romania, HemoCue® was not available so the 132 QuoTest[35] HbA1c Analyser QTD (by EKF Diagnostics) was substituted for Hemocue®. Laboratory 133 HbA1c was estimated from venous blood sample collection taken at the same time as the POC test. 134 All laboratory HbA1c samples were analysed using the HPLC method as per WHO guidelines and were 135 carried out in an accredited laboratory with NGSP certification[36]. 136 Consent and ethical approval 137