Chronic Disease

As media coverage of the new research on sugar exposure and diabetes has expanded, a few readers have asked me why our coverage did not specify that the findings apply only to Type 2 diabetes. The short answer is that the study itself did not distinguish between Type 1 and Type 2 diabetes.

Some quick background: Although both forms of diabetes affect the sugar-handling hormone insulin, the diseases have different origins. Type 1 diabetes is thought to be an autoimmune disease, beginning when, for poorly understood reasons, the body attacks the cells that manufacture insulin. In contrast, Type 2 diabetes occurs when the body stops responding to the insulin it is making. This “insulin resistance” has been thought to be the product of metabolic disturbances associated with overweight and obesity.

The new research, which found an association between sugar countries’ food supplies and diabetes their populations, was based on diabetes rates in adults from 175 countries. Unfortunately, the scientists were not able to obtain data that differentiated between Type 1 and Type 2 diabetes, so they analyzed total diabetes rates.

In the discussion section of the PLOS ONE scientific paper, the researchers address this issue:

“…the International Diabetes Federation database contains diabetes prevalence data based on multiple surveys of varying quality; as many diabetics go undiagnosed, these are likely underestimates, and do not distinguish between Type 1 (approximately 10%) and Type 2 diabetes (90%), which would tend to produce regression towards the mean (underestimating the relationship between sugar and diabetes).”

In other words, the authors expect that if they could get data on Type 2 diabetes rates only, the sugar-diabetes relationship would look even stronger.

But back to Type 1 – do the findings mean that this form of the disease could potentially be caused by sugar? Without data separating the two forms of the disease, we can’t say for sure. But since the scientists know their data is very heavily skewed toward people with Type 2, the reasonable answer is “probably not.”

Previously: New evidence for a direct sugar-to-diabetes link and Sugar intake, diabetes and kids: Q&A with a pediatric obesity expert
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Sugar consumption and diabetes risk may be more closely linked than anyone realized.

For years, research has supported a roundabout path from excess sugar intake to type 2 diabetes. Eat too much of anything, including sugar, and the resulting weight gain raises your diabetes risk, the theory goes. There’s lots of evidence to support this pattern, but also a big hitch: A small but noteworthy proportion of people with type 2 diabetes aren’t overweight or obese. And up to 40 percent of normal-weight people show signs of the metabolic syndrome, a constellation of metabolic disturbances that predisposes people to diabetes.

So what’s going on? New epidemiological evidence, published today in PLOS ONE, suggests that sugar intake may be directly associated with diabetes risk. This research doesn’t refute the sugar-to-obesity-to-diabetes pathway; instead, it suggests that eating too much sugar promotes diabetes in more than one way.

The researchers, who are from Stanford, UC-Berkeley and UC-San Francisco, analyzed a decade’s worth of data on sugar availability in the food supplies and diabetes rates in the populations of 175 countries. They used new statistical methods derived from the field of econometrics to control for several factors that could provide alternate explanations for the relationship between sugar intake and diabetes, including obesity, overweight, sedentary behavior, other calorie sources, and a long list of socioeconomic measures. The statistical controls were more sophisticated than those typically used in biomedical research, the study’s lead author, Sanjay Basu, MD, PhD, explained to me when I interviewed him about the findings. (And for those who want more information about the statistics, Basu has written an interesting post on his personal blog to explain the methods in detail.)

After all the statistical crunching was done, the research showed that every 150-calorie increase in available sugar was associated with a 1 percent increase in the population’s diabetes rate. A 12-oz soda contains about 150 calories of sugar.

From our press release on the study:

Not only was sugar availability correlated to diabetes risk, but the longer a population was exposed to excess sugar, the higher its diabetes rate after controlling for obesity and other factors. In addition, diabetes rates dropped over time when sugar availability dropped, independent of changes to consumption of other calories and physical activity or obesity rates.

The findings do not prove that sugar causes diabetes, Basu emphasized, but do provide real-world support for the body of previous laboratory and experimental trials that suggest sugar affects the liver and pancreas in ways that other types of foods or obesity do not. “We really put the data through a wringer in order to test it out,” Basu said.

…

“As far as I know, this is the first paper that has had data on the relationship of sugar consumption to diabetes,” said Marion Nestle, PhD, a professor of nutrition, food studies and public health at New York University who was not involved in the study. “This has been a source of controversy forever. It’s been very, very difficult to separate sugar from the calories it provides. This work is carefully done, it’s interesting and it deserves attention.”

Previously: Nature/nurture study of type 2 diabetes risk unearths carrots as potential risk reducers and Fighting a fatalistic attitude toward diabetes
Photo by La Piazza Pizzeria

Anyone who has ever eaten a rancid food-truck taco has a gut-level feeling for what it’s like to have the human immune system launch a full-scale attack along 30 feet of intestinal tract. Now you can watch this fascinating process at a microscopic level, pain free, thanks to a new animation posted by Nature: Immunology.

Watching it makes me appreciate the amazing complexity of the human immune system. It also serves as a graphic reminder of how much easier it is to understand these processes when you can see them in action.

Readers interested in irritable bowel syndrome might want to skip to minute 4:00, where the animation shows what happens when pathogens sneak past the gut’s protective mucosal barrier. Spoiler alert: Watch out for the “voracious phagocyte” and the “NETosis explosion.”

Previously: The dawn of a new era in microbiology, Study shows intestinal microbes may fall into three distinct categories and A social networking service for digestive health?

We’ve partnered with Inspire, a company that builds and manages online support communities for patients and caregivers, to launch a patient-focused series here on Scope. Once a month, patients affected by serious and often rare diseases share their unique stories; the latest comes from retired nurse Joan Jahnke.

After 2 ½ years of seeking a definitive diagnosis for my heart disorder, my physician of 14 years told me, “You have been insistent, persistent and consistent each time you presented.” She smiled at me as she said this, and I accepted this compliment as a job well done.

I had been diagnosed with cardiac endothelium dysfunction. I considered the diagnosis a triumph of some sort: Standard tests don’t always identify the disease, and I had gone on quite the journey to identify the source of my problems.

From the beginning, I had stayed focused on my heart symptoms. When various specialists insisted on blaming other organs (gall bladder, uterus, lungs) for my chest pain, I was insistent that they were off target. As a cardiac nurse, I knew that the mounting conflicting test results were confusing, but I felt confident my heart was the issue. After all, I knew myself far better than anyone else could.

Within weeks of my symptom onset, I read an interview with Dr. George Sopko, a cardiologist at the National Institutes of Health, who said, “Women, pay attention to your heart symptoms.” And so, I did that. I began a very succinct journal documenting the timing, duration and quality of chest pain I was experiencing, and I also included what I did to relieve the symptoms. It presented a cause-and-effect pattern with details that supplemented my memory.

I persisted in my search for a definitive diagnosis for my symptoms. My sources were not anecdotal stories from Internet blogs, but instead were scientific papers funded by medical universities and research institutions. I copied medical articles, whose content and format would be most familiar to physicians. I sought out the opinions of medical friends and colleagues, and I approached my research from the perspective of a student – not that of an emotionally distraught woman whose quality of life was rapidly failing.

I remained consistent in my approach. Mindful of how time-consuming difficult diagnoses can be, I came prepared for appointments. I brought with me my ever-present journal, previously prepared questions and medical articles. Many times, my husband would serve as my note-taker, which allowed me to listen closely and concentrate on getting my questions and comments addressed. I offered options for my physicians to consider. I was wrong many times, but never was I rebuffed.

My behaviors culminated in a referral to the Emory Heart Center in Atlanta. By then I was very short of breath, and pain dominated my life. I forwarded my precious journal to the Emory cardiologists, Dr. Jerre Lutz and Dr. Habib Samady, and asked them to read it prior to my appointment. Dr. Lutz knew by page four what was wrong! And he immediately initiated a medical plan of action, in conjunction with Dr. Samady.

My advice to anyone traveling on the difficult road to a diagnosis is to not become the difficult patient – that is, the patient who doesn’t keep track of tests or medication trials as the medical record grows in size, who doesn’t return for appointments, or who disrupts an office practice and makes accusations that no one is listening to his or her complaints. A squeaky wheel doesn’t always get the first or best attention.

Instead, develop a set of behaviors that make you a participant in your healthcare – not merely its recipient. And be insistent, persistent and consistent in your communication and relationship with your physicians.

Joan Jahnke, a retired R.N. with experience in cardiac nursing, lives in South Carolina. She has written about her heart experiences and been active on the Internet since 2008. In 2012, she appeared on a PBS show to discuss how her heart disorder has changed her life, and the difficulties she had in obtaining a diagnosis.

Traci Nagy, the founder of the Feeding Tube Awareness Foundation, grabbed my attention yesterday with a piece she wrote for the Global Gene Project’s website. In it, she discusses the importance of providing support and acceptance to the families of children who need feeding tubes, and she shares her own story:

My son was two months old, and we did not have a full picture of what was going on medically, but we knew he wouldn’t be able to eat enough to live, let alone grow or thrive.

It is difficult to have people stare at your baby for negative reasons. The NG tube was often mistaken for oxygen. Brazen strangers asked what was “wrong” with him or even suggested that he would be better off at the hospital. “Helpful” relatives suggested that we needed second opinions. It wasn’t the full support we needed, particularly with being sleep deprived and emotionally drained.

It took 20 months and dozens of tests to get to the diagnosis of 17q21.31 microdeletion syndrome, recently named Koolen de Vries Syndrome. After diagnosis, I had time to reflect on our journey. The piece that was misunderstood the most was tube feeding, not the missed milestones. Food is different. It is social, it is a reward, it is nurturing, and it is the first bond you have with your child. It is baffling to think a child won’t or can’t eat.

What so many people don’t understand is just how many medical conditions and diseases can lead children to need nutritional support from tube feeding…

Previously: The emotional struggles of parents of preemies

If there’s one single image that universally connotes death, it’s that of a skeleton. But in the living human body, bones are a beehive of activity that, at the cellular level, is as lively and intricate as any dance troupe could perform.

Within the hollows of the long bones dwells a spongy tissue called marrow, which hosts stem cells responsible for the production of both red and a variety of white blood cells. The latter are the warriors, messengers, sentries and medics that compose our immune system. White blood cells defend against microbial invaders and scour our bodies for suspicious cells showing signs of being cancerous. Without our immune systems we wouldn’t last a week.

Whether white or red, blood cells can become cancerous, giving rise to lymphomas and leukemias that, respectively, account for about 45,000 and 75,000 new cases annually in the United States. One effective method of treating these conditions is bone marrow transplantation. In this procedure, the patient’s own blood-forming stem cells are, as thoroughly as possible, wiped out, and then replaced with bone marrow from a donor. From the new bone marrow springs an entire new, cancer-free immune system.

There are two things to watch out for after a tranplant. The first is the possibility that not every single cancerous blood cell was destroyed. The second is the prospect that the new immune system, perceiving its new home in the patient’s body as foreign tissue, may turn its guns on the patient’s own organs – a condition called graft-versus-host disease, or GVHD.

The better the immunological match between donor and recipient, the smaller the chance of the recipient’s developing the unremitting, chronic, form of this syndrome (cGVHD). But when a male recipient gets bone marrow from a woman, there will always be a set of proteins produced from genes on the man’s Y chromosome that the immune cells from the female donor have never come across, says Stanford bone-marr0w-transplant researcher David Miklos, MD, PhD.

As I wrote in our release concerning Miklos’s recent discovery, just published in Proceedings of the National Academy of Sciences, of a blood-borne biomarker that predicts the onset of cGVHD after  female-to-male bone marrow transplants, there’s a trade-off here that often justifies a male leukemia or lymphoma patient’s receiving marrow from a female donor:

While female-to-male bone-marrow transplants put the recipient at 40 percent higher risk of either acute or chronic GVHD than sex-matched transplants, they also reduce the male recipient’s risk of a cancer relapse by 35 percent. Cancer cells are, at heart, unstable and make all kinds of bizarre proteins, fragments of which they tend to display on their surface — a red flag to the immune system. The new immune system is therefore especially vigilant for cancerous cells that somehow survived the effort to destroy them, putting the patient at risk of a relapse.

Miklos has found that the presence of a very particular species of immune cell in the blood of men who’ve received marrow tranplants from women is a strong predictor of impending cGVHD. This early warning that the still asymptomatic condition is developing may may someday allow physicians to administer immune-suppressing drugs that nip cGVHD in the bud.

Previously: Cancer drug shortage implicated in relapses among young Hodgkin lymphoma patients, New leukemia study making waves and Stanford faculty and students launch social media campaign to expand bone marrow donor registry
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Nature and nurture have long been the ‘tomayto’ and ‘tomahto’ of lengthy arguments in both psychology and medicine. At the end of the day, of course, disease is caused neither strictly by genes nor strictly by the environment, but by the interactions between them.

In a new study published in Nature Genetics, Stanford medical-systems expert Atul Butte, MD, PhD (whom I’ve written about at length in the past), has figured out a sophisticated way to crunch massive amounts of genetic and environmental data and pull faint but important signals out of the noise. Sifting through mountains of data gathered in biennial health-and-nutrition surveys run by the federal government’s Centers for Disease Control and Prevention, Butte teased out a gene/environment relationship that may make you want to eat a carrot.

Just over half of us, it’s already known, are walking around with two copies – one from dad, one from mom – of a particular version of a gene that seems to very slightly predispose us to developing type 2 diabetes at some point in our lives. Nothing much we can do about that.

Unlike genes, however, our environment is something we can sometimes do something about. The Butte team’s new work suggests that in people carrying a double dose of the gene version in question, low blood levels of the micronutrient beta-carotene (a vitamin A precursor found copiously in carrots and many other red, orange and yellow vegetables as well as in many vitamin supplements) are associated with not just a slight risk but a significantly increased risk for type 2 diabetes, whereas in those with high blood levels of the substance, that risk appears to be substantially mitigated.

A bit more offbeat is Butte et al.’s finding that another micronutrient – gamma-tocopherol, one of the eight forms of vitamin E – has the opposite interaction with the exact same gene: High levels of it, in people with two copies of the diabetes-related gene version, substantially boost the risk, while low levels reduce it. Nobody knows yet why that’s true, as I explain in our press release:

“We can’t say, based on just this study, that ‘vitamin E is bad for you,’” said [the Human Genetics paper's first author, postdoctoral researcher Chirag Patel, PhD]. He noted that blood levels of alpha-tocopherol - another form of vitamin E that predominates in most supplements - showed no deleterious interaction with the predisposing gene variant in the new study.

But it’s not too early to recommend that people who like carrots keep on eating them. And, the authors speculate, it could be that gamma-tocopherol, rather than being bad in itself, may instead just be a marker of a diet rich in the things where vitamin E is found. This includes soybean, corn, or canola oils (which are, unfortunately, ingredients in many processed and fried foods) and trans-fatty-acid-loaded margarine.

Previously: Mining medical discoveries from a mountain of ones and zeroes, Newly identified type-2 diabetes gene’s odds of being a false finding equal one in 1 followed by 10 zeroes and Cheap data! Stanford scientists’ “opposites attract” algorithm plunders public databases, scores surprising drug-disease hook-ups
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We’ve partnered with Inspire, a company that builds and manages online support communities for patients and caregivers, to launch a patient-focused series here on Scope. Once a month, patients affected by serious and often rare diseases share their unique stories; the latest comes from patient advocate Stan Hardin.

Society teaches us that men are the “tough” ones. Men don’t want to be considered weak, or unhealthy – which is one reason they don’t see their physicians as often as they should.

Ten years ago this past July, when I was 44, I had to overcome my own inhibitions of visiting the doctor I had seen for regular checkups over the years. Those visits were always standard – that is, except for the dreaded “turn your head and cough” moment, when things became uncomfortable for me. So this appointment, during which I was there for the doctor to examine my penis, was a difficult one.

I wound up being diagnosed with Peyronie’s disease, a condition characterized by the formation of fibrous tissue plaques within the tunica albuginea, usually causing a penile deformity and subsequent erectile dysfunction.

My general physician referred me to an experienced urologist who was trained in treating PD. His expertise went further than just treating me physically. He actually took time to sit and talk with me, and his attention on how PD would affect me psychologically and emotionally made all the difference to my being able to cope.

In 2002, with the Internet still in its infancy, there was nothing available online about PD to help me. So I created my own site and, eventually, a nonprofit advocacy organization. With exposure on the Internet came connections with other men suffering from PD, and through this communication I have made several interesting observations.

What stood out most prominently was the men feeling that male physicians themselves were uncomfortable talking to men with PD. Since this is already an awkward situation, any physician who appears this way will make his patients that much more uncomfortable. I believe that the “turn your head and cough” moment resides within the experience of men with PD much more profoundly.

There is also a general feeling of helplessness about this disorder, as evident by two patient comments on our site:

I’m 31, married and too young for PD, I’ve had it for 2 ½ years. The urologist told me to take Vitamin E and that there is no treatment; he scheduled me for a follow up appointment. I never went, what’s the point?

And:

I have had PD for two years… My doctor sent me to a specialist, who told me that if I had been looking at PD on the internet, that I knew more about the disease than he did… I am 57 years old and very surprised at the dismal options for real help out there!

It’s clear to me that any physician who examines a man with PD – and with any “below the waist” disorder – needs to be aware of, and sensitive to, the patient’s uneasiness about being examined and being diagnosed with this type of disease. The importance of communication cannot be overstated.

I now know how fortunate I was to have a urologist who understood the complexity that surrounds a diagnosis of PD, and who came to my level and made me feel comfortable with the disease and talking about it. Even after a diagnosis of PD, I can proudly proclaim that I am still a man – and also an active participant in my health care.

Stan Hardin, of Colorado Springs, Colorado is founder and president of Association of Peyronie’s Disease Advocates, a nonprofit organization dedicated to the education and awareness about PD, The clinical information from the APDA is overseen by some of the most renowned urologists who research Peyronie’s disease and treat men with PD.

Research published today in Pediatrics finds that the use of complementary and alternative medicine (CAM) is common among children, especially those who have been diagnosed with chronic health conditions such as asthma.

In the study, Canadian researchers surveyed 926 parents at two hospitals about their child’s CAM use. The pediatrics patients were being treated for health conditions in one of the following areas: cardiology, neurology, oncology, gastroenterology or respiratory health. Healthland reports:

… half said their children had used the therapies at the same time they were taking conventional drugs, while 10% tried alternative therapies before turning to conventional treatments and 5% used CAM in place of conventional medicine. Yet many parents weren’t telling pediatricians that their children were using CAM, which could increase the possibility of dangerous interactions.

The most commonly used CAM therapies included massage, faith healing, chiropractic and aromatherapy, while the most popular products to treat conditions ranging from cancer to asthma and inflammatory bowel disease were vitamins and minerals, herbal remedies and homeopathic medicines.

…

In the U.S., a recent survey found that one in nine children had used alternative therapies to treat a health condition. Vohra says parents’ own beliefs about and reliance on CAM therapies is a major factor behind its use in children, as is parents’ desire to provide their children with every possible health option. “For most parents, their number one priority is the health of their children so they’re interested in exploring all options to promote their children’s health,” says [Sunita Vohra, MD, lead author of the study.] “Many parents consider all products that are available and seek out not only conventional health care but also complementary health care.”

Previously: NIH to host Twitter chat on complementary medicine and children, Study shows meditation may lower teens’ risk of developing heart disease, New NIH series offers consumer-friendly tips on complementary health practices and Report highlights how integrative medicine is used in the U.S.
Photo by Wellcome Images

I’ve written at some length in the past about “the brain’s silent majority“: the 90 percent of the cells in our central-nervous system that aren’t nerve cells. Collectively called ”glia” (a rather demeaning term that comes from the Greek word for glue),  this collection of non-nerve brain cells has long gone unsung.

Stanford neurobiologist Ben Barres, MD, PhD, has been in the forefront of research proving that, despite their relatively sparrowlike demeanor in comparison to nerve cells’ pyrotechnic bursts of electrochemical activity, the three glial cell types – astrocytes, oligodendrocytes, and microglia – are silent superstars, juggling scores of tasks crucial to brain development and function.

In a just-published review in Science, Barres and two colleagues describe the role of microglia (which – unlike nerve cells or the other glial-cell types, all descended from brain-based precursor cells - trace their developmental origins to the immune system) in brain health. The upshot: Malfunctioning microglia may underlie many neurodegenerative conditions worrisome to an aging population as well as to physicians and researchers.

Barres and his co-authors write:

The meaning of the term “inflammation” has undergone considerable evolution. Originally defined by Celsus’ four cardinal signs of “tumor, rubor, calor et dolor” [swelling, redness, heat, and pain], inflammation typically [involves the leakage] of blood cells [from the bloodstream into tissues]…. The word “neuroinflammation,” however, is increasingly used to identify a radically different set of conditions … specific to the central nervous system (CNS). Whereas viral, bacterial, and autoimmune diseases of the CNS can resemble their [non-nervous-system] counterparts [in formal appearance], the concept of “neuroinflammation” has gradually expanded to also describe diseases that display none of Celsus’ cardinal signs, [that] do not attract conventional inflammatory cells, and that most neuropathologists would classify as degenerative rather than inflammatory. These “inflammatory” changes are restricted to a cell type exclusive to the CNS: the microglia.

Among the many jobs performed by microglia is their surveillance of the entire brain for signs of injury, to which they rapidly respond by migrating to the site, tackling pathogens, and gobbling up damaged nerve-cell components to speed repair. Another item on the microglial resume is what the Science review’s authors call the “sculpting of neural circuits”: Microglia help prune away excessive or inappropriate brain-cell connections.

But one can readily imagine how that latter process, if it gets out of hand, could cause problems. The authors suggest that the pathological underpinnings of not only neurodegenerative diseases such as Alzheimer’s but even so-called neurodevelopmental conditions including autism-spectrum and obsessive-compulsive disorders – not traditionally thought of as inflammatory - may turn out to harbor a microglial component. “As our tools and technology for studying microglia grow,” they write, “so too will our understanding of their role in the healthy brain.”

Previously: Unsung brain-cell population implicated in variety of autism, Brain police: Stem cells’ fecund daughters also boss other cells around, Research shows eating berries may boost brain health
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