Associated Risk Factors for Latent Tuberculosis Infection in Subjects with Diabetes

Background and Aims

Type 2 diabetes mellitus (DM2) confers a higher risk for active tuberculosis (TB). However, information on associated risk factors for latent tuberculosis infection (LTBI) inpatients with DM2 is limited. We conducted a cross-sectional study to elucidate the prevalence of LTBI and its associated factors on Mexican adults with DM2 receiving medical care at the Mexican Social Security Institute (IMSS).

Methods

Six hundred patients with DM2 without a prior history of TB from outpatient diabetes clinics were enrolled in the study. The tuberculin-skin-test (TST) was performed. The presence of LTBI was defined by a TST value of ≥5 mm. A standardized interview and physical examination were conducted to obtain clinical, demographic, and LTBI risk factor information; all subjects were laboratory tested to determine the presence of exclusion criteria. Microscopic examination of sputum samples and chest x-rays was performed to identify potential active TB. Subjects with any finding suggesting active TB or malignancy were excluded. A logistic regression model was used to identify variables associated with LTBI.

Results

LTBI prevalence among patients with DM2 was 51.3%. Risk factors for LTBI were living with a relative with TB, having been in prison, having hemoglobin values >14 g/dL, and glycosylated hemoglobin (HbA1c) values of >7%. Blood pressure, economic income, or anthropometric measurements were not associated risk factors.

Conclusions

Over one half of patients with DM harbor LTBI. Exposure to certain environmental conditions and poorly controlled DM2 (HbA1c >7.0%) were risk factors for having LTBI in persons with DM2.

Introduction

According to the World Health Organization (WHO), 347 million persons worldwide are currently suffering from diabetes mellitus (DM), mainly type 2 diabetes mellitus (DM2) (1), one third of the world's population has latent tuberculosis infection (LTBI) and 8.6 million individuals developed tuberculosis (TB) in 2012 (2). In the same year, The Ministry of Health in México reported a TB prevalence of 16.8 cases/100,000 inhabitants, without official data regarding LTBI prevalence. In Mexico, the bacillus Calmette-Guérin (BCG) vaccine is applied at birth with a coverage of >95% (3). The association between DM and TB has been suggested for some time 4, 5; however, comorbidities of these diseases were not reported until 80 years ago and are now firmly established 6, 7. The association between these diseases is of greater importance for populations with low socioeconomic status and high prevalence rates of both conditions (6) but, as the result of globalization and high migration rates, detecting patients with DM and who are at risk for active TB is a global public health challenge (8). As in other countries, in Mexico there is an increase in the frequency of TB among patients with DM2, and a higher frequency of DM2 among individuals with TB, regardless of whether human immunodeficiency virus (HIV) infections have been reported 6, 9, 10, 11. Given the worldwide distribution of these pathologies, the comorbidity of DM2-TB is expected to occur more frequently in regions with low income and/or poor healthcare services (6). Other risk factors for the comorbidity of active TB in patients with DM include low body weight (12), poor glycemic control 13, 14, 15, 16 and nutritional deficiencies 17, 18.

It is well known that DM affects the immune system, impairing chemotaxis, phago- and monocyte activity, and also increasing T-cell activity. All these alterations are present during acute hyperglycemia 14, 19. In addition, in patients with DM2, a decrease in circulating levels of Interferon gamma (IF-γ), interleukin 2 (IL-2), tumor necrosis factor α (TNF-α), and IL-17F (all of these implicated in the immune control of TB) have been reported (20). Although the association between DM2 and active TB is well established 9, 11, 21, the factors involved in the association between DM2 and LTBI are scarcely known and there are discrepancies 22, 23, 24 or no association at all 25, 26, 27. Over one quarter of patients with DM2 harbor LTBI 11, 22, 23, 24. Given that reactivation of LTBI is influenced by the immune system, subjects with DM and LTBI may carry a greater risk for TB reactivation.

The tuberculin skin test (TST) is the most used diagnostic test for LTBI, and it measures the cellular immune response against Mycobacterium tuberculosis (Mtb) antigens. Considering that patients with DM2 present deficiencies with regard to the immunity 28, 29, it is possible that the current cut-off value for TST considered to detect LTBI in patients with DM2 is higher than it should be; therefore, it exhibits lower sensitivity with respect to persons without DM2.

To gain insight into the association of LTBI and DM2, we conducted a cross-sectional study aimed at determining the risk factors associated with LTBI in Mexican adults with DM2 and the prevalence (using a TST ≥5-mm cut-off point) of LTBI in patients affiliated with the Mexican Social Security Institute (IMSS) in Durango and Zacatecas, states located in northern Mexico.