Glycemic Control and the Risk of Tuberculosis: A Cohort Study

Abstract

Background: Diabetes is a well-known risk factor for tuberculosis (TB) and is increasingly prevalent in low- and middle-income countries, where the burden of TB is high. Glycemic control has the potential to modify the risk of TB. However, there are few studies on the association between glycemic control and TB risk, and the results are inconsistent.

Methods and findings: We assembled a cohort using 123,546 individuals who participated in a community-based health screening service in northern Taiwan from 5 March 2005 to 27 July 2008. Glycemic control was measured using fasting plasma glucose (FPG) at the time of screening. The cohort was followed up to 31 December 2012 for the occurrence of TB by cross-matching the screening database to the national health insurance database. Multiple imputation was used to handle missing information. During a median follow-up of 4.6 y, 327 cases of TB occurred. In the multivariable Cox regression model, diabetic patients with poor glycemic control (FPG > 130 mg/dl) had a significantly higher hazard of TB (adjusted hazard ratio [aHR] 2.21, 95% CI 1.63-2.99, p < 0.001) compared to those without diabetes. The hazard of TB in diabetic patients with good glycemic control (FPG ≤ 130 mg/dl) did not differ significantly from that in nondiabetic individuals (aHR 0.69, 95% CI 0.35-1.36, p = 0.281). In the linear dose-response analysis, the hazard of TB increased with FPG (aHR 1.06 per 10-mg/dl increase in FPG, 95% CI 1.03-1.08, p < 0.001). Assuming the observed association between glycemic control and TB was causal, an estimated 7.5% (95% CI 4.1%-11.5%) of incident TB in the study population could be attributed to poor glycemic control. Limitations of the study include one-time measurement of fasting glucose at baseline and voluntary participation in the health screening service.

Conclusions: Good glycemic control could potentially modify the risk of TB among diabetic patients and may contribute to the control of TB in settings where diabetes and TB are prevalent.

Fig 1. Kaplan-Meier plot of tuberculosis-free survival by diabetes mellitus and glycemic control status, adjusted for age.

The blue line (“Non-DM”) represents nondiabetic participants; the red line (“DM with GC”) represents diabetic patients with good glycemic control (FPG ≤ 130 mg/dl); the green line (“DM with PC”) represents diabetic patients with poor glycemic control (FPG > 130 mg/dl).

Fig 2. Dose-response curves for fasting plasma glucose and risk of incident tuberculosis in the Cox proportional hazards model.

The red line and orange dashed lines represent the point estimates and 95% confidence intervals from the nonlinear analysis using penalized spline regression; the blue line represents the point estimates from the linear analysis. Model 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. All variables were adjusted for as categorical variables (see Table 1 for details) except for age, frequency of outpatient visits, and BMI (as continuous variables). HR, hazard ratio.