Effect of glycemic control and type of diabetes treatment on unsuccessful TB treatment outcomes among people with TB-Diabetes: A systematic review

Abstract

BackgroundStringent glycemic control by using insulin as a replacement or in addition to oral hypoglycemic agents (OHAs) has been recommended for people with tuberculosis and diabetes mellitus (TB-DM). This systematic review (PROSPERO 2016:CRD42016039101) analyses whether this improves TB treatment outcomes.ObjectivesAmong people with drug-susceptible TB and DM on anti-TB treatment, to determine the effect of i) glycemic control (stringent or less stringent) compared to poor glycemic control and ii) insulin (only or with OHAs) compared to ‘OHAs only’ on unsuccessful TB treatment outcome(s). We looked for unfavourable TB treatment outcomes at the end of intensive phase and/or end of TB treatment (minimum six months and maximum 12 months follow up). Secondary outcomes were development of MDR-TB during the course of treatment, recurrence after 6 months and/or after 1 year post successful treatment completion and development of adverse events related to glucose lowering treatment (including hypoglycemic episodes).MethodsAll interventional studies (with comparison arm) and cohort studies on people with TB-DM on anti-TB treatment reporting glycemic control, DM treatment details and TB treatment outcomes were eligible. We searched electronic databases (EMBASE, PubMed, Google Scholar) and grey literature between 1996 and April 2017. Screening, data extraction and risk of bias assessment were done independently by two investigators and recourse to a third investigator, for resolution of differences.ResultsAfter removal of duplicates from 2326 identified articles, 2054 underwent title and abstract screening. Following full text screening of 56 articles, nine cohort studies were included. Considering high methodological and clinical heterogeneity, we decided to report the results qualitatively and not perform a meta-analysis. Eight studies dealt with glycemic control, of which only two were free of the risk of bias (with confounder-adjusted measures of effect). An Indian study reported 30% fewer unsuccessful treatment outcomes (aOR (0.95 CI): 0.72 (0.64−0.81)) and 2.8 times higher odds of ‘no recurrence’ (aOR (0.95 CI): 2.83 (2.60−2.92)) among patients with optimal glycemic control at baseline. A Peruvian study reported faster culture conversion among those with glycemic control (aHR (0.95 CI): 2.2 (1.1,4)). Two poor quality studies reported the effect of insulin on TB treatment outcomes.ConclusionWe identified few studies that were free of the risk of bias. There were limited data and inconsistent findings among available studies. We recommend robustly designed and analyzed studies including randomized controlled trials on the effect of glucose lowering treatment options on TB treatment outcomes.

Global prevalence of diabetes in active tuberculosis: a systematic review and meta-analysis of data from 2·3 million patients with tuberculosis

“…This need for evidence is supported by the potential benefit of treating diabetes and improving glycaemic control on tuberculosis treat ment outcomes. [3][4][5] This study should, however, be interpreted in the con text of some drawbacks. First, we included 200 studies among which 81 (41%) and 31 (16%) had a moderate and high risk of bias, respectively.…”

“…2 Diabetes triples the risk of developing tuberculosis, and poor glycaemic control adversely affects tuberculosis treatment outcomes with effects such as prolongation of culture conversion, treatment failure, relapse, and death. [3][4][5] Furthermore, diabetes accounted for 10·6% of global tuberculosis deaths among HIVnegative individuals in 2015. 6 With 425 million people affected by diabetes globally in 2017, and a predicted 48% increase up to 629 million people who would have diabetes in 2045, it is foreseeable that this surge in the prevalence of diabetes will contribute to increase the incidence of tuberculosis.…”

Stress Hyperglycemia in Patients with Tuberculosis Disease: Epidemiology and Clinical Implications

“…A meta-analysis of the effect of diabetes on TB treatment outcomes found that patients with diabetes had approximately twice the odds of death (pooled odds ratio [OR] 2.1, 95% confidence interval [CI] 1.8–2.5) and TB relapse (pooled OR 1.8, 95% CI 1.4–2.3) compared to patients without diabetes [56]. However, the majority of studies that estimated an association between diabetes and adverse TB outcomes did not stratify by previously diagnosed diabetes, undiagnosed pre-existing diabetes, or extent of hyperglycemia, and none have estimated the effect of stress hyperglycemia on TB treatment outcomes [57]. …”

“…Another study from Peru that measured diabetes medication use among 136 patients with TB and diabetes reported the highest risk of poor TB outcome among those receiving only insulin (38%) during TB treatment as compared to those receiving oral hypoglycemic agents (14%) or both (12%) [60]. Overall, studies that estimated the effects of glycemic levels on TB outcomes have heterogeneous results [57], likely due to the timing of glucose levels measurements, severity of TB disease at baseline, type of diabetes care, and the complex amalgamation of patients with TB and previously diagnosed diabetes, undiagnosed pre-existing diabetes, and stress hyperglycemia.…”

Diabetes mellitus comorbidity in patients enrolled in tuberculosis drug efficacy trials around the world: A systematic review

“…A recent systematic review showed that glycaemic control has a favourable effect on TB treatment outcomes and, conversely, uncontrolled DM or poor glycaemic control (i.e. HbA1c > 7%) was associated with delayed sputum conversion …”