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July 10, 2009
NIH Podcast Episode #0088
Balintfy: Welcome to episode 88 of NIH Research Radio with news about the ongoing medical research at the National Institutes of Health—the nation's medical research agency. I'm your host Joe Balintfy. Coming up in this episode: some stories about discovery: in one report we learn about the unexpected diversity of microbes found on the skin; also we’ll here more about how scientists have discovered a new genetic immune disorder in children. But first: how people with type 2 diabetes can reduce their risk. That's next on NIH Research Radio.
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Ask Your Health Care Team About Your Type 2 Diabetes
Balintfy: Heart disease is the number one cause of death for people with type 2 diabetes.
Dr. Rodgers: In fact, two of three patients with diabetes will suffer and die from a heart attack or a stroke.
Balintfy: Dr. Griffin Rodgers, director of the National Institute of Diabetes and Digestive and Kidney Diseases, says because of this and other problems such as blindness, kidney failure, and lower limb amputations, it is important for people with diabetes to set goals to manage their disease.
Dr. Rodgers: I think it’s very important to pick a realistic goal, and something that one can stick with, and set that goal, write it down, and then work toward that goal.
Balintfy: Goals can include increasing physical activity, making better food choices and managing blood sugar levels better. Dr. Rodgers recommends working with a health care team to monitor the ABCs of diabetes.
Dr. Rodgers: The A stands for the hemoglobin, the A1C, and that’s a general measure of the average glucose or sugar control in the preceding two to three months. Typically, for most patients, we like that A1C value to be less than seven percent. The B stands for blood pressure, and for most patients with type 2 diabetes, a target for that blood pressure should be less than 130/80. C stands for cholesterol, or the so-called bad cholesterol, or LDL cholesterol, we typically like that target to be 90 or less.
Balintfy: Keeping blood glucose, blood pressure and cholesterol close to these target levels reduces risk for the long-term problems of diabetes. Dr. Rodgers emphasizes that a health care team will know if medications are working.
Dr. Rodgers: In general we think that patients should have at least two visits with their health care provider over the course of the year, at which point the hemoglobin A1C should be measured.
Balintfy: Dr. Rodgers adds that additional exams, like an eye exam, are recommended annually.
Dr. Rodgers: In addition, of course, we’re looking for evidence of kidney damage, so a urine and a blood test to look for so-called diabetic nephropathy is important. Looking for evidence of disease in the foot, and so a foot examination, using fibers to examine the touch and feeling sensation there is a good way to look for nerve damage that might accompany diabetes as ulceration. Hopefully we’ll prevent patients going on for requiring amputations in their feet.
Balintfy: Dr. Rodgers emphasizes that people with type 2 diabetes ask their health care team questions about the disease, as well as prevention and treatment goals. Patients and health care professionals can get more information from the National Diabetes Education Program by calling 1-888-693-NDEP or visiting www.yourdiabetesinfo.org.
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Study Finds Unexpected Bacterial Diversity on Human Skin
Balintfy: The health of our skin—one of the body’s first lines of defense against illness and injury—depends upon the delicate balance between our own cells and the millions of bacteria and other one-celled microbes that live on its surface. To better understand this balance, National Institutes of Health researchers have set out to explore the skin’s microbiome, which is all of the DNA, or genomes, of all of the microbes that inhabit human skin. Their initial analysis, published recently in the journal Science, reveals that our skin is home to a much wider array of bacteria than previously thought. Alaya Levi Salley has this story.
Levi Salley: In order to maintain healthy skin, it is essential to have just the right balance of the body’s own cells and microbes—tiny organisms that include bacteria.
Segre: We need to think about that there are bacteria that are promoting our health and move away from thinking of them as our adversaries but rather as our allies.
Levi Salley: Dr. Julia Segre, Senior Investigator at the National Human Genome Institute explains that researchers are taking a closer look at microbes by using the power of modern DNA sequencing technology. Compared to traditional research methods that involved growing microbial samples—or cultures—in the laboratory, these new findings show unexpected bacterial diversity on the skin.
Segre: We’ve always suspected that there was probably 100 bacteria that we couldn’t find for every one, but now we have names for them and we know what they are so that we can change the culture conditions and try to grow them and use this as a baseline for then seeing how the microbioda, the small microorganisms, how their communities change in disease states.
Levi Salley: Understanding the complex genetic and environmental factors involved in skin conditions like eczema, psoriasis, acne, antibiotic-resistant infections and many other skin disorders may lead to new and better strategies for treating and preventing skin diseases. Dr. Segre explains that microbe samples were taken from 20 different sites on the bodies of 10 healthy volunteers. These sites represent three distinct microenvironments: oily, moist, and dry.
Segre: We’re analyzing what bacteria live at all different depths of your skin, and with these methods, the diversity that we found is about 100 times greater than what was previously known.
Levi Salley: In the study, the greatest bacterial diversity of about 44 specie types was found on the forearm. The least amount of diversity was found behind the ear with only 19 specie types. Bacterial samples were taken from body locations pre-disposed to skin disease. Some locations were sampled twice over a 4-6 month period to closely examine how bacterial communities change with time. While Dr. Segre says the study reinforces the benefit of some bacteria, she also points out the importance of continuing basic public health practices such as hand washing.
Segre: This study underscores what we’ve known all along. We have to focus on the sanitation. We have to focus on washing our hands and not bringing bacteria from the environment onto our bodies or bringing bacteria from one place in our bodies to another.
Levi Salley: Dr. Segre explains that the study, published in the journal Science, is part of a bigger initiative.
Segre: This year the NIH Roadmap for Medical Research, launched the Human Microbiome Project, whose aim is to study the diversity of bacteria that live in and on the human body, assessing then the bacterial diversity on the skin, the vagina, the nose, the gut, and the oral cavity and are also funding projects that begin to examine the correlation between disease states and the microbiome.
Levi Salley: For more information on this study and the Human Microbiome Project, visit www.nihroadmap.nih.gov/hmp. This is Alaya Levi Salley, National Institutes of Health, Bethesda, Maryland.
Balintfy: More about how a rare genetic immune disorder was discovered, and the good news about its treatment, next. Stay tuned.
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DIRA Interview
Balintfy: Last episode, we featured a report about how scientists have discovered a new genetic immune disorder in children. Now we talk more with Dr. Raphaela Goldbach-Mansky. She’s from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Goldbach-Mansky, can you remind us again, what exactly is the immune system?
Goldbach-Mansky: The immune system developed to actually defend us against &madsh; or defend our body against &madsh; harmful influences from the outside. And they can actually be viral or bacterial infections, or any other form of danger, including UV lights, or dying cells within our body, or other noxious agents that we are exposed to or produce in our system.
Balintfy: Now in autoinflammatory diseases, however, the immune system goes awry, causing unprovoked and dangerous inflammation. And you published findings in the New England Journal of Medicine about a new autoinflammatory syndrome. Can you explain what you found?
Goldbach-Mansky: We identified a novel disease that occurs in children at the time they are born, and has — is life-threatening, particularly in the early months of life. The disease is caused by a genetic mutation in one of the innate immune system genes that actually lead to the fact that this protein is not expressed. And the protein, IL-1 receptor antagonist — it has a very long name — is actually a break in the immune system. It was actually developed by our system to down-regulate some immune responses, to make them less strong, and in the absence of the protein the immune response just goes full-blown and causes damage to the organs, to a number of organs that are actually affected in that disease.
Balintfy: The disease is called DIRA – deficiency of the IL-1 receptor antagonist. Dr. Goldbach-Mansky, can you explain how the DIRA discovery was made?
Goldbach-Mansky: Yeah, that was actually quite exciting. About two years ago, I heard of — I received a referral from a patient in Newfoundland who did have a neonatal disease that reminded the physicians treating the child of another neonatal disease that I treat and have protocols on, neonatal onset multisystem inflammatory disease, or NOMID, a disease which also has a genetic defect in the IL-1 pathway and is effectively treated by an IL-1 blocking agent called anakinra. So the child had been in the intensive care unit for over five months, and no treatment they had applied, including antibiotics and steroids, had made a marked impact on this child, and they were wondering if this child had mutation-negative NOMID. After discussions of the signs and symptoms, we concluded that anakinra might be a reasonable choice in that situation, and if the child in fact responded, a diagnosis of mutation-negative NOMID might be possible. They started anakinra, and within days, literally, the rash disappeared, the bone lesions had healed, the inflammatory markers that were elevated in the blood before treatment normalized, and within two weeks the child was discharged to go home. Four months later, the child came to the NIH for enrollment into my NOMID study, and a review, a careful review of the clinical signs and symptoms. Pictures, over 100, that the mother had taken during the development in the ICU revealed that this is a novel disease, that this clearly was not NOMID. But the effective treatment had given us a hint that the abnormality might be within the IL-1 pathway, because blocking IL-1 effectively treated that disease. And I contacted Dr. Aksentijevich in Dan Kastner’s lab, to look for mutations in other parts of the IL-1 pathway, which she did, and in fact the third gene she picked in the IL-1 pathway was IL-1 receptor antagonist. And she in fact found that the infected child was homozygous, so it actually had two copies of a mutated gene that led to the non-expression of IL-1 receptor antagonist, the very protein we actually gave the child as a treatment, which anakinra is, a recombinant form of the IL-1 receptor antagonist.
Balintfy: What are the common features of people with DIRA?
Goldbach-Mansky: So the common features of children are that — are a rash that develops during the perinatal period. They can either be born with a rash, or it develops within the first few weeks of life. The children start to become painful and actually cry when they’re being picked up, and that is due to osteolytic lesions in the bone that look like infections in the bone, however all blood cultures are negative. And the children develop very high markers of inflammatory — or indicating inflammation, systemic inflammation in the blood, like sedimentation rate or a C-reactive protein. Typically, they don’t get fever, but they look very sick. They don’t eat very well, and they basically are non-active, they don’t move because of the bone pain associated with the syndrome.
Balintfy: But people with DIRA respond well to treatment, right?
Goldbach-Mansky: Yeah, that is correct. As I mentioned before, blocking the IL-1 pathway with anakinra, the protein the children are lacking, is very effective. It has to be given by daily injection, but there are other longer-acting IL-1 blocking agents that are being developed that might be effective, and I am in fact interested in testing one of such agents in those patients. The discovery has had immediate health impacts. We’ve started a collaboration with a group in Puerto Rico to determine the prevalence of DIRA in Puerto Rico by studying newborn samples, identifying carrier families, and the Puerto Rican group is working on a protocol to counsel such patients and implement prenatal identification of carriers and possibly affected patients. And I’ve had a request by the health department in Puerto Rico, who is working on developing a fact sheet that they will distribute to pediatric clinics, first of that area, and once we better know what the prevalence of the disease is, probably wider in Puerto Rico, to actually help identify and treat such patients.
Balintfy: To date, how many patients are believed to have the disease?
Goldbach-Mansky: I currently know — we have described nine patients. Since the paper has been published, I’ve heard of eight more cases. So we don’t have a very good idea of the prevalence. We have looked at different populations where this mutation might be a founder mutation, where it might be carried more frequently. One is the Puerto Rican population, particularly the Northwestern part. If our preliminary estimates are correct, the carrier frequency of the mutation would be 2.3 percent in the Northwestern population, and about 1 in every 6,300 children born in that region would have the disease. I, in fact, one day after our paper was published, I received a call from the University Hospital in Miami, and they in fact had a 3-months-old child in the ICU, which was diagnosed on the basis of the paper, and is now effectively treated. Both parents are from Puerto Rico. So within Puerto Rico and within the population in Puerto Rico, outside, in U.S. mainland, there might actually be a considerable number of patients, I would think maybe between 100 and 200 at this point.
Balintfy: Thank you very much Dr. Goldbach-Mansky. Is there anything you would emphasized about DIRA?
Goldbach-Mansky: I think it is important to emphasize that the disease gets diagnosed very early on, so that damage to the bones and life-threatening inflammatory response syndrome could actually be avoided, and also that children do not get unnecessarily treated with antibiotics or get biopsied multiple times, as the characteristics of this disease is very classic, and can — as this disease can be diagnosed without, actually, biopsies.
(THEME MUSIC)
Balintfy: Thanks again to Dr. Raphaela Goldbach-Mansky at the National Institute of Arthritis and Musculoskeletal and Skin Diseases. For more on her study and DIRA, visit the website www.niams.nih.gov. That’s it for this episode of NIH Research Radio. Please join us again on Friday, July 24 when our next edition will be available for download. I'm your host, Joe Balintfy. Thanks for listening.
NIH Research Radio is a presentation of the NIH Radio News Service, part of the News Media Branch, Office of Communications and Public Liaison in the Office of the Director at the National Institutes of Health in Bethesda, Maryland, an agency of the US Department of Health and Human Services.
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