Diabetes Set to Undermine Success in Global TB Control

Becky McCall

September 05, 2014

Improving diabetes prevention and care helps control tuberculosis (TB), especially in low- and middle-income countries where rates of TB are highest and where the incidence of type 2 diabetes is rising sharply, according to an expert at the World Health Organization (WHO) and lead author of a series of 3 new papers exploring links between the 2 diseases.

Published online September 4 in Lancet Diabetes & Endocrinology, the review papers prompt the suggestion that patients with either diabetes or TB need to be cross-checked for the other disease and highlight the need to reconsider the clinical management of these difficult-to-treat patients.

The comprehensive work not only shines a spotlight on how the rising incidence of type 2 diabetes could hamper global efforts to control and eliminate TB but advises how healthcare systems in low- and middle-income countries should tackle the double burden and how diabetes is likely to affect TB outcomes over the next 20 years.

In fact, the series indicates that 15% of adult TB cases worldwide are already attributable to diabetes, with more than 40% occurring in India and China alone. The next 8 nations with the highest estimated number of adult TB cases associated with diabetes are South Africa, Indonesia, Pakistan, Bangladesh, the Philippines, Russia, Burma, and the Democratic Republic of Congo.

The lead author, Knut Lönnroth, MD, medical officer at WHO, Geneva, Switzerland, says the situation highlights how "public-health planning should not happen in boxes, like dividing up communicable and noncommunicable diseases into distinct categories, but across health issues, disciplines, and sectors."

TB needs to stay on the clinical radar when caring for people with diabetes, especially patients who are likely to have been exposed and infected with the TB bacilli.

From a clinical perspective, Dr. Lönnroth added, "TB needs to stay on the clinical radar when caring for people with diabetes, especially patients who are likely to have been exposed and infected with the TB bacilli." He pointed out that this not only applies to the majority of people with diabetes in low- to middle-income countries but also populations originating from TB-endemic regions migrating to wealthier countries.

"Conversely, diabetes should be on the clinical radar when caring for people with TB….This is important in all settings and for all TB patients," he stressed, adding that "diabetes can go undiagnosed for a long period, so it makes sense to do proactive screening for diabetes in all patients with TB."

Conversely, diabetes should be on the clinical radar when caring for people with TB.

The authors also note that despite success in reaching the Millennium Development Goal of reversing the incidence of TB by 2015, control efforts are being undermined by the rising incidence of type 2 diabetes and obesity.

This message echoes that given during a presentation at the World Diabetes Congress 2013, reported by Medscape Medical News, which drew attention to the growing problem of concurrent diabetes and TB in low- and middle-income countries and the deleterious effect of diabetes on gains in TB control.

Diabetes Increases Susceptibility to TB, Reduces Treatment Response

In the series of reviews, the authors point out that diabetes triples the risk of TB and is also a risk factor for adverse TB treatment outcomes, including relapse and death. Consequently, the increasing burden of type 2 diabetes will help to sustain the present tuberculosis epidemic.

Referring to findings derived from mathematical modeling featured in the series, the researchers warn that if the necessary diabetes-control measures fail, then the present downward trajectory in global TB cases could experience 8% less reduction, or even more, by 2035.

Specifically, the first paper reports that a 52% increase in diabetes prevalence recorded over the past 3 years in the 22 highest-TB-burden countries is considered responsible for a rise in diabetes-associated TB cases from 10% in 2010 to 15% in 2013.

The reasons underpinning the susceptibility of diabetes patients to TB are not fully understood, but impairment of both the innate and the adaptive immune system is considered to play a significant part.

"Poor glycemic control seems to worsen the situation. Once [a person is] infected with mycobacterium tuberculosis, diabetes is one of several factors that increase the risk of progression to active TB disease, as seen in approximately 10% of infected people," the scientists say.

Infection stays dormant in the majority of people, but, cautioned Dr. Lönnroth, "any dormant infection with TB is a ticking bomb. With the impaired immune system of a patient with diabetes, the bacilli take opportunity to replicate and increase risk of active disease."

Post-2015 Global TB Targets: Diabetes Prevention Can Help

In the third paper of the series, Dr. Lönnroth and his coauthors stress that to achieve the post-2015 global TB target of 90% reduction in TB incidence by 2035, the present rate of decline must accelerate. Among factors that hinder TB control, malnutrition and diabetes are key challenges, they note.

Exploring both ends of the spectrum from the most pessimistic to the most optimistic scenarios, they detail how future trends in diabetes would affect the burden of TB.

In this respect, "the most important finding is that there is great potential for improved diabetes prevention to have a significant positive impact on TB prevention," said Dr. Lönnroth in an interview with Medscape Medical News.

Effective interventions such as optimal diabetes management or chemoprophylaxis of latent TB to reduce the risk of active TB in diabetes patients could be beneficial. However, they add that trials are needed to substantiate these suggestions.

They also note that in many low- and middle-income countries, where high rates of social and health inequalities persist, body mass index distribution actually clusters around extreme values. "In many of these countries, diabetes coexists with undernutrition, a situation with the potential to detrimentally affect tuberculosis burden," they observe.

Meanwhile, the second paper in the series looks specifically at clinical management of patients with concurrent diabetes and TB.

Drawing attention to the difficulties of successfully treating such patients, the authors highlight that tuberculosis patients with diabetes have a reduced concentration of tuberculosis drugs and a higher risk of drug toxicity than tuberculosis patients without diabetes.

And good glycemic control, "which reduces long-term diabetes complications and could also improve tuberculosis treatment outcomes, is hampered by chronic inflammation, drug-drug interactions, suboptimum adherence to drug treatments, and other factors," they point out.

"Diabetes is associated with increased risk of tuberculosis treatment failure, death, and relapse, but whether optimum glucose control can partly or fully mitigate these negative effects and whether tuberculosis treatment should be adjusted in patients with diabetes is uncertain," they acknowledge.

And they add that more evidence is needed to support measures including screening and subsequent treatment for latent TB infections in patients with diabetes.

Screening Key in Endemic Regions; Mirror Example Set By TB and HIV

The WHO has developed a new global TB strategy post-2015 (approved by the 67th World Health Assembly in May 2014). One of the key actions called for is intensification of early detection of TB.

Dr. Lönnroth explained the importance of awareness among clinicians of the potential coexistence of both diseases in low- and middle-income countries.

"Where TB and diabetes rates are high and where delayed or missed diagnosis is common for both diseases, clinicians need to be alert for comorbidities. They need to consider systematic bidirectional screening and optimizing and coordinating management to improve early detection and clinical outcomes for both. Coordinated health program planning will be important to achieve this."

He stressed, however, that systematic screening for TB in people with diabetes, regardless of clinical picture, should be considered only where TB rates are high. "If TB rates are low, the number needed to screen to detect 1 case of TB is very high, even among people with diabetes."

From a clinical perspective, an increased index of suspicion for TB is important during treatment of diabetes in all settings. "Most important, it should be considered early as a differential diagnosis for people with diabetes who develop respiratory symptoms."

An accompanying editorial emphasizes that in tackling the burgeoning epidemic of concurrent diabetes and TB and the pressure it places on healthcare services, it might be valuable to use the example set by tackling TB in patients with HIV.

"The care models in place for dealing with patients with HIV and tuberculosis can potentially be used to provide a framework for those needed to treat people with diabetes and tuberculosis."

The editorial comment continues by noting, "Importantly, the intersection between communicable diseases and [noncommunicable diseases] should be used as a driver to strengthen health systems and to ensure that they can provide access to care with financial risk protection for all disorders, not just a select few."

Dr. Lönnroth has declared no relevant financial relationships. Disclosures for the coauthors are listed in the articles.

Lancet Diabetes Endocrinol. 2014;2:730–739 (Article), 740-753 (Article), 754-764 (Article) 677 (editorial).


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