Review
Tuberculosis and diabetes mellitus: convergence of two epidemics

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Summary

The link between diabetes mellitus and tuberculosis has been recognised for centuries. In recent decades, tuberculosis incidence has declined in high-income countries, but incidence remains high in countries that have high rates of infection with HIV, high prevalence of malnutrition and crowded living conditions, or poor tuberculosis control infrastructure. At the same time, diabetes mellitus prevalence is soaring globally, fuelled by obesity. There is growing evidence that diabetes mellitus is an important risk factor for tuberculosis and might affect disease presentation and treatment response. Furthermore, tuberculosis might induce glucose intolerance and worsen glycaemic control in people with diabetes. We review the epidemiology of the tuberculosis and diabetes epidemics, and provide a synopsis of the evidence for the role of diabetes mellitus in susceptibility to, clinical presentation of, and response to treatment for tuberculosis. In addition, we review potential mechanisms by which diabetes mellitus can cause tuberculosis, the effects of tuberculosis on diabetic control, and pharmacokinetic issues related to the co-management of diabetes and tuberculosis.

Introduction

The association between diabetes mellitus and tuberculosis and their synergistic role in causing human disease has been recognised for centuries. Ancient works by Yugimahamuni, an Indian siddhar, describe the symptoms of patients with “meganoikal” (urinary disorders), which progressed from obesity to impotence, thirst, and glycosuria, and ultimately, to unconsciousness or tuberculosis.1 The introduction of insulin in the 1920s, the discovery of streptomycin in the 1940s, and the subsequent development of other antibiotics substantially lowered case fatality rates for individuals with diabetes mellitus or tuberculosis. Improved sanitation, better nutrition, and less crowding led to markedly diminished tuberculosis incidence. In recent decades, tuberculosis has increasingly become a problem in low-income countries, particularly those with HIV epidemics, and non-insulin-dependent diabetes mellitus (NIDDM) has emerged as a growing worldwide chronic health condition, as a consequence of increases in obesity, changing patterns of diet and physical activity, and aging populations.2, 3, 4, 5 The effect of diabetes on the development and severity of tuberculosis, and the complex inter-relations between nutrition, obesity, diabetes, and tuberculosis remain provocative issues in public health and clinical medicine.6, 7, 8 In the setting of the increasing overlap of populations at risk for both diseases, the combination of tuberculosis and diabetes mellitus represents a worldwide health threat.

Our aim was to evaluate the published work and synthesise a concise Review of the following topics: the epidemiology of diabetes mellitus and tuberculosis disease; the effect of diabetes mellitus on tuberculosis incidence, radiographic presentation, severity, and outcomes; the potential mechanisms by which diabetes mellitus increases tuberculosis incidence; the cause–effect relation of tuberculosis on incident diabetes mellitus; and the pharmacological issues in cotreatment of tuberculosis and diabetes mellitus.

Section snippets

Double burden of tuberculosis and diabetes

The burden of communicable diseases is concentrated in low-income countries. However, non-communicable diseases, which represented 47% of the disease burden in 1990 in low-income countries, have been predicted to rise to 69% by 2020.9 Increasing industrialisation and urbanisation leads to higher rates of obesity and diabetes. The number of people with diabetes, which was 171 million in 2000, is expected to grow to 366 million–440 million by 2030, with three-quarters of patients with diabetes

Effect of diabetes on tuberculosis risk and severity

Historically, the incidence of tuberculosis in patients with diabetes has been high.23, 24 In 1934, a treatise on the association between diabetes and tuberculosis was written by Howard Root (a physician at the Deaconess Hospital, Boston, MA, USA), before the availability of antimycobacterial drugs.24 His lengthy tome described the epidemiology, pathology, and clinical course of dually affected patients. In his studies, tuberculosis in adults with diabetes was more common than expected, and

How might diabetes mellitus lead to tuberculosis?

Poorly controlled diabetes can lead to multiple complications, including vascular disease, neuropathy, and increased susceptibility to infection.74 Diabetes might also lead to increased susceptibility to disease caused by M tuberculosis via multiple mechanisms. The mechanisms include those directly related to hyperglycaemia and cellular insulinopenia, as well as indirect effects on macrophage and lymphocyte function, leading to diminished ability to contain the organism.

The most important

Does tuberculosis lead to diabetes?

If diabetes can predispose a patient to tuberculosis, can infection with tuberculosis lead to diabetes mellitus? Infections, including tuberculosis, often worsen glycaemic control in diabetic patients, and poorly controlled diabetes might in turn augment the severity of infections.85 Some studies suggest that tuberculosis can even cause diabetes in those not previously known to be diabetic. Many studies have used oral glucose tolerance testing to show that patients with tuberculosis have higher

Pharmacological issues in the co-management of diabetes mellitus and tuberculosis

Infections are known to worsen diabetic control, and tuberculosis is no exception. Although tuberculosis can cause glucose intolerance and might predispose patients to diabetes mellitus, the drugs used to treat tuberculosis might also worsen glycaemic control in patients with diabetes. Overlapping toxicities must also be considered when co-managing tuberculosis and diabetes, such as peripheral neuropathy caused by treatmetn with isoniazid. Given the risk of peripheral neuropathy, pyridoxine

Future research

In reviewing and summarising the published work on the complex relation between tuberculosis and diabetes mellitus and their respective treatments, we have found that many important topics have been poorly studied or not studied at all. Although tuberculosis is clearly more common in diabetic patients, several questions remain unanswered that would greatly affect the clinical management of the two diseases and, thus, merit increased attention: does diabetes mellitus lead to increased

Search strategy and selection criteria

We searched the PubMed database on three occasions over 2 years by use of the following search terms: (“tuberculosis”[MeSH Terms] OR “tuberculosis”[All Fields]) AND (“diabetes mellitus”[MeSH Terms] OR “diabetes mellitus”[All Fields] OR “diabetes”[All Fields] OR “NIDDM”[All Fields] OR “IDDM”[All Fields]). The date reange of the search was from June, 2007, to August, 2009. We searched EMBASE by use of a similar search strategy. A hand search of references in included articles as well as

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