Diabetes Mellitus Increases the Risk of Active Tuberculosis: A Systematic Review of 13 Observational Studies

Abstract

Background

Several studies have suggested that diabetes mellitus (DM) increases the risk of active tuberculosis (TB). The rising prevalence of DM in TB-endemic areas may adversely affect TB control. We conducted a systematic review and a meta-analysis of observational studies assessing the association of DM and TB in order to summarize the existing evidence and to assess methodological quality of the studies.

Methods and Findings

We searched the PubMed and EMBASE databases to identify observational studies that had reported an age-adjusted quantitative estimate of the association between DM and active TB disease. The search yielded 13 observational studies ( n = 1,786,212 participants) with 17,698 TB cases. Random effects meta-analysis of cohort studies showed that DM was associated with an increased risk of TB (relative risk = 3.11, 95% CI 2.27–4.26). Case-control studies were heterogeneous and odds ratios ranged from 1.16 to 7.83. Subgroup analyses showed that effect estimates were higher in non-North American studies.

Conclusion

DM was associated with an increased risk of TB regardless of study design and population. People with DM may be important targets for interventions such as active case finding and treatment of latent TB and efforts to diagnose, detect, and treat DM may have a beneficial impact on TB control.

Abstract

In a systematic review and meta-analysis including more than 17,000 tuberculosis cases, Christie Jeon and Megan Murray find that diabetes mellitus is associated with an approximately 3-fold increased risk of tuberculosis.

Editors' Summary

Background.

Every year, 8.8 million people develop active tuberculosis and 1.6 million people die from this highly contagious infection that usually affects the lungs. Tuberculosis is caused by Mycobacterium tuberculosis, bacteria that are spread through the air when people with active tuberculosis cough or sneeze. Most infected people never become ill—a third of the world's population is actually infected with M. tuberculosis—because the human immune system usually contains the infection. However, the bacteria remain dormant within the body and can cause disease many years later if host immunity declines because of increasing age or because of other medical conditions such as HIV infection. Active tuberculosis can be cured by taking a combination of several antibiotics every day for at least six months, and current control efforts concentrate on prompt detection and carefully monitored treatment of people with active tuberculosis to prevent further transmission of the bacteria.

Why Was This Study Done?

Despite this control strategy, tuberculosis remains a major health problem in many countries. To reduce the annual number of new tuberculosis cases (incidence) and the number of people with tuberculosis (prevalence) in such countries, it may be necessary to identify and target factors that increase an individual's risk of developing active tuberculosis. One possible risk factor for tuberculosis is diabetes, a condition characterized by high blood sugar levels and long-term complications involving the circulation, eyes and kidneys, and the body's ability to fight infection. 180 million people currently have diabetes, but this number is expected to double by 2030. Low- to middle-income countries (for example, India and China) have the highest burden of tuberculosis and are experiencing the fastest increase in diabetes prevalence. If diabetes does increase the risk of developing active tuberculosis, this overlap between the diabetes and tuberculosis epidemics could adversely affect global tuberculosis control efforts. In this study, the researchers undertake a systematic review (a search using specific criteria to identify relevant research studies, which are then appraised) and a random effects meta-analysis (a type of statistical analysis that pools the results of several studies) to learn more about the association between diabetes and tuberculosis.

What Did the Researchers Do and Find?

From their search of electronic databases, the researchers found 13 observational studies (nonexperimental investigations that record individual characteristics and health outcomes without trying to influence them in any way) that had examined whether diabetes mellitus increases the risk of active tuberculosis. Diabetes was positively associated with tuberculosis in all but one study, but the estimates of how much diabetes increases the risk of developing active tuberculosis were highly variable, ranging from no effect to an increased risk of nearly 8-fold in one study. The variability may represent true differences between the study populations, as higher increases in risk due to diabetes was found in studies conducted outside of North America, including Central America, Europe, and Asia; or it may reflect differences in how well each study was done. This variability meant that the researchers could not include all of the studies in their meta-analysis. However, the three prospective cohort studies (studies that follow a group of individuals with potential risk factors for a disease over time to see if they develop that disease) that they had identified in their systematic review had more consistent effects estimates, and were included in the meta-analysis. This meta-analysis showed that, compared to people without diabetes, people with diabetes had a 3-fold increased risk of developing active tuberculosis.

What Do These Findings Mean?

These findings support the idea that diabetes increases the risk of tuberculosis, a biologically plausible idea because, in experimental and clinical studies, diabetes was found to impair the immune responses needed to control bacterial infections. The 3-fold increased risk of tuberculosis associated with diabetes that the meta-analysis reveals suggests that diabetes may already be responsible for more than 10% of tuberculosis cases in countries such as India and China, a figure that will likely increase as diabetes becomes more common.

However, the estimate of this impact is based on three cohort studies from Asia; other studies suggest that the extent of the impact due to diabetes may vary by region and ethnicity. In populations where diabetes affects the risk of tuberculosis to a similar or greater extent, global tuberculosis control might benefit from active case finding and treatment of dormant tuberculosis in people with diabetes and from increased efforts to diagnose and treat diabetes.

Additional Information.

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050152.

• The US National Institute of Allergy and Infectious Diseases provides information on all aspects of tuberculosis

• The US Centers for Disease Control and Prevention provide several fact sheets and other information resources about tuberculosis

• The World Health Organization provides information (in several languages) on efforts to reduce the global burden of tuberculosis, including information on the Stop TB Strategy and the 2008 report Global Tuberculosis Control—Surveillance, Planning, Financing

• The US Centers for Disease Control and Prevention provides information for the public and professionals on all aspects of diabetes

• The US National Institute of Diabetes and Digestive and Kidney Diseases also provides information about diabetes (in English and Spanish)