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A Dual Threat

Diabetes has become dangerously linked to a new form of tuberculosis

A Dual Threat

If you have diabetes and are unfortunate enough to live in or visit an area where there is a lot of tuberculosis (TB), or if you know someone with TB, you may be at special risk. A simple chronic cough that won’t seem to go away, pain in the chest and a poor appetite could be a sign that you are among many people throughout the world who are particularly susceptible to catching TB. If you already have diabetes and you do get TB, it can sometimes be resistant to treatment, take longer to heal and be more likely to relapse.

TB in people with Type 2 diabetes has been described by researcher Susan P. Fisher-Hoch, M.D., as the “pandemic of the 21st century.” Currently, there are at least 382 million people affected by diabetes worldwide. By 2035, the International Diabetes Federation and the World Health Organization (WHO) estimate that this will increase to nearly 600 million people. These numbers are not only alarming but the growing rates of diabetes will lead to many serious health problems. Most of these we know about, such as heart or kidney disease. But the new one is the re-emergence of the association with a sometimes fatal infectious disease: TB.

TB is an infectious disease of the lungs considered to be the number one bacterial killer worldwide. The illness especially affects people with impaired immune systems often caused by chronic and/or progressive conditions such as malnutrition, aging, smoking and HIV/AIDS. While HIV/AIDS has been the leading host factor for TB for years, diabetes is slowly taking over that role. 

“The problem is not that AIDS is an unimportant risk; rather, it is that there are well over 10 times as many people globally with diabetes as with AIDS,” says Fisher-Hoch, professor in the Division of Epidemiology, Human Genetics and Environmental Sciences at The University of Texas Health Science Center at Houston (UTHealth) School of Public Health Brownsville Regional Campus. “Many of those with diabetes are also in countries with high burdens of TB.”

In the United States, we are used to TB being the burden of prisoners, drug and alcohol abusers and HIV/AIDS patients. Diabetes patients are quite different, and usually do not have these other risk factors. They can be your average housewife going to market or your elementary school teacher. Much is changing in this new risk of TB that emerges with diabetes. 

Researchers at the UTHealth School of Public Health Brownsville Regional Campus were among the first to show that people with diabetes are three-to-five times more likely to develop TB than those without diabetes when exposed to the disease. 

The risk of TB is growing among patients with poorly managed diabetes, according to Fisher-Hoch. She has worked in many countries in Africa and Asia on TB and other diseases, and with her colleagues Joseph B. McCormick, M.D., who also worked on TB in Asia, and Blanca I. Restrepo, Ph.D., published some of the early data about TB and diabetes. Fisher-Hoch also contributed to publication of the WHO framework on diabetes and TB and recently wrote a comprehensive review article on the subject for Research and Reports in Tropical Medicine.

A new dilemma

The connection between diabetes and TB was long known prior to the 1950s, but the patients had Type 1 juvenile diabetes, and the problem was virtually eliminated with the development of insulin to manage diabetes and drugs to treat TB.

Today, however, we face a new dilemma with the growing number of people affected by Type 2 diabetes, which now accounts for 90 percent of reported diabetes cases. After a slow start, WHO has now identified diabetes as a neglected, important and re-emerging risk factor for TB. In India and China the problems are even greater with an increase in Type 2 diabetes due to urbanization and the growth of fast food restaurants, but a continuing background of TB so that many people are exposed. In some states in India, diabetes has nearly doubled the rate of TB infections. In addition, it now appears that even patients with pre-diabetes are more susceptible to TB.

“Diabetes patients with TB often have difficulty completing treatment, take longer to be cured and are more likely to relapse, even die, and develop drug-resistant TB,” says Fisher-Hoch.

Rio Grande Valley “hot spot”

At UTHealth, researchers are working to understand the underlying factors that have contributed to the large number of TB cases that have emerged in the Rio Grande Valley of Texas, where obesity and diabetes rates are incredibly high. In Brownsville, 80 percent of adults are overweight or obese.

“Thirty percent of our adult population here has diabetes. That’s as much or more than anywhere else in the country,” says Fisher-Hoch.

In the United States, TB rates are disproportionately higher among racial/ethnic minorities, according to the Centers for Disease Control and Prevention (CDC). In a study done by UTHealth researchers in 2011, 25 percent of TB cases found in Mexicans and Mexican-Americans along the border were attributed to the presence of diabetes. In contrast, only 6 percent of the TB cases were due to HIV.

“The Rio Grande Valley is like a test tube for the rest of the world when it comes to the association of diabetes and TB,” says Restrepo, an associate professor in the Division of Epidemiology, Human Genetics and Environmental Sciences at UTHealth School of Public Health Brownsville Regional Campus. The study conducted in Brownsville has implications for other diabetes and TB crises around the world as it reflects what can happen in a population with high rates of obesity.

Drug-resistant TB

Multi-drug-resistant TB has been described as a “public health crisis” by WHO. The organization estimates that there are half a million incident cases of drug-resistant TB globally, which accounts for 3.6 percent of all TB cases. Unfortunately, in most places, isolates are not made and so patients are not tested for drug resistance. The problem is undoubtedly much larger than it appears.

Those who suffer from multi-drug resistant TB have a treatment failure rate of nearly 50 percent. Drug-resistant TB was more common in diabetes-related infections in the Rio Grande Valley study, and this has now been shown in studies with larger numbers of patients from all over the world, particularly in countries with high-burden TB.

It’s difficult to test for drug-resistant TB as it requires isolation of the organism or molecular testing, both of which have limited availability due to a lack of resources and technical limitations, especially in low-income areas.

A sign of hope

Health care providers, patients and communities need to be educated about the connection between diabetes and TB to promote dual screening. Caregivers and people with diabetes also need to be aware when visiting neighborhoods or countries where TB is common.

“We need strong investment in research and development of TB vaccines, rapid and inexpensive diagnostic methods for both TB and diabetes and fast-acting, easy-to-take TB medication,” says Fisher-Hoch.

“The key issue is thinking of the two diseases together and screening for both in endemic areas” says McCormick, Regional Dean and James H. Steele Professor in the Division of Epidemiology, Human Genetics and Environmental Sciences at UTHealth School of Public Health Brownsville Regional Campus.

The good news is that this research has brought attention to the issue, and policy changes are in motion. Fisher-Hoch is a member of the StopTB board for the United States, and she was invited to present her data at a recent meeting of the National Tuberculosis Controllers Association in Atlanta. Fisher-Hoch explained the growing rates of diabetes and TB in Texas and found an ally in attendee Sandra Morris.

Morris is the manager of the TB and Refugee Health Services Branch of the Texas Department of State Health Services (DSHS). She presented these new observations to the TB Expert Panel of DSHS who discussed the problems in Texas and voted for routine screening for diabetes for all patients at TB clinics across the state. They are currently preparing the recommendation for commissioner review. Screening for TB among diabetes patients is a more difficult issue, as is deciding on recommendations for the specific needs of diabetes patients being treated for TB.  These issues are now in the public eye and new clinical research and further policy changes will be needed. “This is a story of public health research leading to policy changes, but the job is yet unfinished” says Fisher-Hoch.

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