Double Trouble: Diabetes and TB are 2 Converging Pandemics

December 03, 2013

MELBOURNE, Australia — The burgeoning epidemic of diabetes in lower- and middle-income countries is threatening to undo decades of hard work in the field of infectious disease, with tuberculosis control in particular a major concern, World Diabetes Congress 2013 attendees heard here on the meeting's opening day .

Most cases of diabetes — 80% — are now occurring in the developing world, in low- and middle-income countries, and those with diabetes — regardless of whether it is type 1 or type 2 — are at higher risk of contracting TB, Anil Kapur, MD, from the World Diabetes Foundation, Gentofte, Denmark, told the meeting during a session on novel complications of diabetes. Diabetes increases the risk for active TB 2- to 3-fold, with the risk being higher the poorer the glucose control.

And research also indicates that those with infectious diseases are more likely to develop diabetes, he noted. "We know that type 1 diabetes is an autoimmune disease triggered by viral infections, but in fact, there is evidence to suggest that inflammation and immune responses might play a role in type 2 diabetes as well," he explained. Data show those with periodontitis, Helicobacter pylori infection, and hepatitis C are around 2 to 3 times more likely to develop type 2 diabetes, for example, with the evidence "strongest" for hepatitis C.

Dr. Anil Kapur

But by far the biggest issue is primary tuberculosis, Dr. Kapur stressed. "Unfortunately, today we are faced with a huge challenge: the 2 largest countries with the highest risk of endemic TB — China and India — are also the countries with the highest burden of diabetes. Therefore, the 2 epidemics are converging, and it's a 'syndemic' that's happening," he stressed. Some studies indicate that as many as half of all those infected with TB in countries like these have coexisting diabetes, about half of which remains undetected, he noted. "We are missing a lot of people with TB who have underlying diabetes, and this has consequences for the overall outcome."

The issue is important because people with both conditions suffer worse sequelae. For a start, people with diabetes come to clinics all the time and are therefore more exposed to infections than the general population, Dr. Kapur explained. And when they do contract TB, it manifests itself in a different way from the disease seen in those with TB who do not have diabetes — it "tends to affect the lower lung lobes, with pulmonary microangiopathy," and is more akin to the TB seen in patients with HIV infection, he noted. One of the consequences of this is that it seems to take longer to cure TB in those with diabetes, approximately 3 months more, than it does in patients who don't have diabetes. In addition, inflammation distorts glycemic control and can therefore have a negative impact on some of the complications of diabetes, such as ischemic heart disease and kidney failure.

Most important, "the risk of dying from TB in people with diabetes is about 4 to 5 times higher than in people with TB who do not have diabetes," he stressed.

And undiagnosed diabetes among those with TB is the flip side of the coin. "Why should people with TB die in modern times with the availability of good anti-TB drugs? They die because they have diabetes that is not being detected and properly managed," Dr. Kapur emphasized.

"The public-health systems are not prepared. People working in the field of diabetes discount infections, and people working in the field of TB have focused all their attention on HIV infection. They forget there are 40 million people with HIV infection but 400 million with diabetes, and while the individual risk [for TB] is about 7 times higher with HIV infection and about 3 times higher with diabetes, from a population perspective point of view, diabetes is today a much bigger threat for TB control than HIV," Dr. Kapur told Medscape Medical News.

How to Tackle This Problem?

The best way of trying to tackle this "dual epidemic", said Dr. Kapur, is to routinely screen those with TB for diabetes, ideally using HbA1c testing but, failing that, with an oral glucose tolerance test or fasting blood sugar.

"The number of TB cases needed to screen to find 1 diabetes case is generally very low… You [only] need to screen roughly 8 to 10 cases of diabetes to identify 1 or 2 new case of diabetes, and we are likely to find a lot of people with TB who have diabetes who have not been identified," he explained. In most developing countries, "it should be a routine public-health measure to screen people with TB for diabetes, and it's not that expensive to do that."

"The other way around is a little more complicated," he cautioned, although the "association between diabetes and TB is not in doubt. We know that diabetes impairs the immune response to TB."

Data from India indicated that the incidence of TB in those with diabetes is about 8 times higher than in the general community, and figures from China suggest it's about 6 times higher, "but because TB is much rarer in the community than diabetes…you will need to screen 150 to 250 cases of diabetes with a symptom screen to find 1 case of TB."

Nevertheless, in countries where TB is endemic, "it is prudent that diabetes clinics do ask patients and do a symptom screen every 6 months to a year to pick up cases of TB faster." This is not difficult to do, he stresses. The simplest way is to initially ask diabetes patients attending clinics if they have had any symptoms of TB. "If a patient has a persistent wet cough for 2 weeks, with productive sputum and a low-grade fever," these signs are indicative of TB, and such patients can then be referred for chest X-ray and further examination.

And given that in many parts of the world, TB is treated with directly observed medical therapy (DOTS), the healthcare workers administering TB medications are ideally placed to screen for diabetes, Dr. Kapur noted.

He emphasized that trial data are still needed to examine whether extending current TB regimens in those with diabetes from 6 months of therapy to 9 months will bear fruit; such studies are ongoing.

Asia Pacific Region Most Badly Affected

The largest burden of TB is in Southeast Asia, which contributes to about 40% of the world's total; the same region makes up 20% of the global burden of diabetes, Dr. Kapur explained. Meanwhile, the Western Pacific region has 36% of the burden of diabetes and 20% of the world's TB cases.

"So between the Western Pacific region and Southeast Asia we have roughly a 60% burden of both TB and diabetes," he observed.

"About 80 years ago, almost everybody in Europe with diabetes used to die of TB, and there used to be common clinics for diabetes and TB. In those times, the developing world did not have the burden of diabetes, and once effective treatment for TB was found, this risk declined very rapidly," he noted.

But it's now time once more to monitor these 2 conditions together, he stressed, and fortunately, there is hope on the horizon. In 2011, the International Union on TB and Lung Disease and the WHO Stop TB Program developed a collaborative framework for care and control of TB and diabetes.

As a consequence of this, free testing has been taking place in some countries. In 2013, for example, the Indian government instituted a policy to screen all patients with TB for diabetes in 100 districts where a national program already existed for prevention and control of cancer, cardiovascular disease, and stroke. Subsequent to this, it extended the program, so that all 13,000 centers nationwide where there is a facility to do a TB sputum screen will now be provided with a glucometer.

But he observed, "We need to gather more evidence to push this agenda. We hope that China will take the same decision that India has taken."

Dr. Kapur emphasized that "382 million people are affected by diabetes; there are 10 million new cases every year and 5.1 million deaths." And there are around 12 million people with TB who either are cured or die and therefore they don't accumulate.

"Diabetes and TB are 2 converging pandemics. Continuing to ignore and underplay this association will undo decades of painstaking gains in TB control and prove disastrous both in terms of health and economics," he concluded.

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