TAG: "Diabetes"

More isn’t always better

Study links increased diabetes risk, higher levels of testosterone to prostate enlargement.

Michael Gurven, UC Santa Barbara

By Andrea Estrada, UC Santa Barbara

Benign prostatic hyperplasia (BPH) — or, simply, prostate enlargement — is one of the most common diseases of aging among men in the United States. In fact, by the time they hit 80 or above, upwards of 90 percent of all men in the U.S. experience some degree of prostate enlargement. And of those, 40 percent require medical treatment.

Despite the fact that the disease impacts so many people and carries with it a huge price tag — estimated at tens of billions of dollars per year in medical expenses and lost wages, among other costs — the factors that contribute to BPH have yet to be positively identified.

However, a new study conducted by UC Santa Barbara anthropologists suggests that the hormone testosterone — specifically, an unnatural overabundance thereof — may be a prime culprit. Building on previous research they conducted with the Tsimane, an isolated indigenous population in central Bolivia, Benjamin Trumble and Michael Gurven examined the prevalence of BPH among a group of approximately 350 adult males.

Benjamin Trumble, UC Santa Barbara

Within that group, advanced cases of prostate enlargement were practically non-existent. As a correlating factor, the Tsimane also have relatively low levels of testosterone that remain constant over their lives.

“Abdominal ultrasounds show they have significantly smaller prostates — an age-adjusted 62 percent smaller prostate size — as compared to men in the U.S.,” said Trumble, a postdoctoral scholar at UCSB and the paper’s lead author. “BPH is not inevitable for Tsimane men.” The researchers’ work appears in the Journals of Gerontology: Medical Sciences.

“We also know testosterone and androgens are involved because of studies showing that eunuchs and people who don’t have testes have very low rates of BPH,” Trumble added. “Some of the best pharmacological BPH and prostate cancer treatments involve reducing androgen levels. We also know from our own previous research that Tsimane have relatively low levels of testosterone — about 30 percent lower than age-matched U.S. males — and they have very low rates of obesity and hypertension and heart disease and all the other diseases of acculturation, including metabolic disease.”

Despite having low testosterone overall, Tsimane men with higher testosterone levels (but still significantly lower than those of men in industrial populations) have larger prostates. According to the researchers, this has important implications for the millions of men who use testosterone supplements to counteract low testosterone. They may be putting themselves at risk for prostate enlargement.

“Basically, these guys taking testosterone replacement therapies are entering themselves into an uncontrolled experiment,” said Trumble. “And this happened to women with estrogen replacement therapy from the 1980s to the early 2000s. And then the Women’s Health Initiative study came out and showed that all these women were putting themselves at risk for breast and other cancers.”

Although this particular study did not test for prostate cancer, other studies have shown that population differences in testosterone impact prostate cancer risk as well, according to Trumble. “Populations with higher testosterone exposure appear to have higher rates of prostate cancer,” he said. “And similar to those for BPH, many of the pharmacological treatments for prostate cancer block androgens.”

The researchers’ findings raise questions about the health benefits — and risks — that come from our attempts to thwart Mother Nature. “In American men, testosterone levels decrease with age,” said Gurven, a professor of anthropology and senior author of the paper. Gurven also is co-director of the Tsimane Health and Life History Project, a joint effort of the University of New Mexico and UCSB. “It’s easy to look at that pattern and think, ‘Well, if I want to reverse the aging process, I only need to return to the high levels of testosterone of my vigorous youth.’

“But there’s probably a reason your body is producing less testosterone than it used to, and if you try to trick it and flood it with testosterone supplements, you may see some beneficial effects — people report feeling more energized, having a stronger libido — but at what cost?” he continued. “Perhaps even if you knew the costs, you’d still make the decision to use testosterone replacement therapy and discount the risks relative to the potential gains, but understanding those risks is vital in order to make an informed decision.”

The bottom line: More long-term studies of testosterone replacement therapy in men are necessary to ensure its safety and efficacy.

“Something else we found is that even the men who did have anatomical BPH beyond a certain cutoff, the size that would require treatment in the U.S., those were exceedingly rare,” said Trumble. “About 50 percent of men in their 70s in the U.S. have prostates larger than 40 cubic centimeters, which is the level where they start looking at major medical interventions. For the Tsimane, less than 1 percent of all men in the study had prostates larger than 40 cubic centimeters.

“Not only were they smaller, but those that were relatively larger were still much smaller than what you’d see in the U.S.,” Trumble added, “and smaller than what would require treatment.”

In addition to measuring prostate size, the researchers looked at the levels of glycated hemoglobin in the subjects’ blood. Glycated hemoglobin — HbA1c — is a measure of long-term glucose exposure that in turn indicates the risk of diabetes. “Despite having subclinical levels of HbA1c, men with higher HbA1c had larger prostates,” said Trumble. “Not one of the men in this study had HbA1c indicative of diabetes. These were all men with relatively low glucose levels.

“Among men with low testosterone and low diabetes risk, those with relatively higher testosterone or HbA1c were at higher risk of prostate enlargement,” he said.

But what does the health and wellness of the Tsimane, a population of hunters and forager-farmers, tell us about ourselves?

“The Tsimane are living under conditions that are more typical of our preindustrial past,” explained Gurven. “Working with populations like the Tsimane gives us a nice window into how traditional lifestyles and environments — subsistence diet, physical activity, natural fertility, infectious exposure and kin-based social networks — can shape health and well-being.” The types of chronic diseases that afflict us today may manifest because of the relatively rapid changes in all these factors over the past several hundred years, he noted. Although gene frequencies continue to change, he said, we’re still fundamentally “Stone Agers in the fast lane.”

“Type 2 (adult onset) diabetes is one of these illnesses that under more traditional conditions wouldn’t be as prevalent as it is today in high-income countries, or becoming increasingly prevalent in urban areas of low-income countries,” Gurven said. “As groups of the Tsimane undergo change, we might very well see an increase in diabetes. Then it wouldn’t be surprising if heart disease, BPH and other modern maladies follow suit, especially to the extent that these ailments share common causes.

“It’s a great example of evolutionary medicine in which understanding our human biological history is really important in terms of the way we think about medicine,” he added.

In the end, the researchers argue, prostate enlargement is not necessarily an inevitable part of male aging. It is a disease that our low-pathogen, resource-abundant sedentary lifestyle is creating for us.

Other researchers contributing to the study include Hillard S. Kaplan of the University of New Mexico; Jonathan Stieglitz of the University of New Mexico and the Institute for Advanced Study in Toulouse, France; and Daniel Eid Rodriguez and Edhitt Cortez Linares of the Tsimane Health and Life History Project in San Borja, Bolivia.

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Drug that can prevent onset of diabetes is rarely used

Metformin is inexpensive, effective for people with pre-diabetes, but few take it.

Tannaz Moin, UCLA

By Enrique Rivero, UCLA

Few doctors are prescribing a low-cost drug that has been proven effective in preventing the onset of diabetes, according to a UCLA study. The study, published in the peer-reviewed journal Annals of Internal Medicine, found that only 3.7 percent of U.S. adults with pre-diabetes were prescribed metformin during a recent three-year period.

Metformin and lifestyle changes both can prevent the onset of diabetes, but people often struggle to adopt healthier habits, according to Dr. Tannaz Moin, the study’s lead author and an assistant professor of medicine in the division of endocrinology at the David Geffen School of Medicine at UCLA and at VA Greater Los Angeles.

“Diabetes is prevalent, but pre-diabetes is even more prevalent and we have evidence-based therapies like metformin that are very safe and that work,” Moin said. “Metformin is rarely being used for diabetes prevention among people at risk for developing it. This is something that patients and doctors need to be talking about and thinking about.”

It is estimated that about one-third of adults in the U.S. have pre-diabetes, which is marked by higher-than-normal blood sugar levels.

The American Diabetes Association in 2008 added metformin to its annual “Standards for Medical Care in Diabetes” guidelines for use in diabetes prevention for those at very high risk who are under age 60, are severely obese, or have a history of gestational diabetes. Under the guidelines, metformin may also be considered for patients whose blood sugar is above normal but not yet in the diabetes range.

The researchers examined data from 2010 to 2012 from UnitedHealthcare, the nation’s largest private insurer, for a national sample of 17,352 adults aged 19 to 58 with pre-diabetes. They also found:

  • The prevalence of metformin prescriptions was 7.8 percent for severely obese patients.
  • Metformin prescriptions were nearly twice as high for women (4.8 percent) as for men (2.8 percent).
  • Among people with pre-diabetes, the prevalence of prescriptions for obese individuals was 6.6 percent, versus 3.5 percent for non-obese people.
  • Among people who had pre-diabetes and two other chronic diseases, 4.2 percent received prescriptions for metformin, versus 2.8 percent of people with pre-diabetes and no other chronic diseases.

The reasons for the underuse of metformin are not clear, the researchers write, but they could include a lack of knowledge of the 2002 Diabetes Prevention Program Study, which showed that both lifestyle changes and metformin use can prevent or delay progression to diabetes among those with pre-diabetes, the fact that the drug does not have FDA approval for pre-diabetes and reluctance by patients and doctors to “medicalize” pre-diabetes.

“Identifying more effective ways to help people avoid diabetes is essential to individuals’ lives and to society as a whole, which is why it was important to us to support this research,” said Dr. Sam Ho, a co-author of the study and chief medical officer of Minnetonka, Minnesota-based UnitedHealthcare.

Potential limitations to the study included a lack of access to data on participation in lifestyle programs; possible misclassification of pre-diabetes and metformin use; the fact that the analysis focused on adults with commercial insurance, which could make the findings inapplicable to uninsured or older adults; and the researchers’ inability to independently verify patients’ eligibility to receive metformin under the American Diabetes Association guidelines.

The study’s co-authors are Jinnan Li, O. Kenrik Duru, Susan Ettner, Norman Turk and Carol Mangione of UCLA; and Abigail Keckhafer of UnitedHealthcare.

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Higher BMI associated with reduced costs, better health for diabetics

UC Davis researchers recommend defining types of type 2 diabetes.

Anthony Jerant, UC Davis

By Karen Finney, UC Davis

It’s a paradox: Diabetics with above-normal weight use health care less and report overall better physical health than their diabetic counterparts with normal weight, according to two new studies from UC Davis Health System. The authors suggest that the extra weight isn’t protecting diabetics as commonly assumed, but that normal-weight people with diabetes are afflicted with a more severe form of the disease.

Prior studies found that diabetics with normal BMIs have a higher mortality risk than those who are overweight or obese.

“The mortality paradox led to the ‘protection explanation’ that seems unlikely to be true because we didn’t see any beneficial effects of excess weight in people who did not have diabetes,” said Anthony Jerant, professor of family and community medicine at UC Davis and lead author of the studies. “The possibility that there is more than one form of type 2 diabetes is supported by basic science studies showing physiological differences in leaner people with diabetes.”

For their research, Jerant and his colleagues evaluated data on about 120,000 patients in the 2000-2011 Medical Expenditures Panel Surveys (MEPS), an annual assessment from the U.S. Department of Health and Human Services on health status, medical services and health care costs among a representative sample of U.S. civilians.

Characterized by unstable blood sugar levels, diabetes is currently diagnosed as type 1, an unpreventable form typically diagnosed in children or young adults, or type 2, which mostly affects adults and is linked with unhealthy lifestyles. Because the vast majority — about 90 percent — of the nearly 30 million diabetics in the U.S. have type 2, the study results are most applicable to type 2 diabetes.

In a study published online March 20 in the journal Medical Care, the UC Davis team compared health care expenditures, hospitalizations and emergency department visits for those with and without diabetes and in relation to their BMIs (normal, overweight or obese), a standard measure of weight adjusted for height. For all three study criteria, health care utilization was significantly higher in normal weight than in heavier diabetic persons, differences that were not observed in those who did not have diabetes.

In another study published online April 27 in the journal Nutrition & Diabetes, the researchers evaluated results of self-reported physical and mental health status for patients with and without diabetes. Overall, those with diabetes had worse physical and mental health status than non-diabetic persons. Among just those with diabetes, physical health status was better for those who were either overweight or obese as compared to those who had normal weight, and most optimal for those who were overweight.

Jerant believes the new findings provide evidence that it’s time to quit thinking that leaner type 2 diabetics are at lower risk for bad outcomes from the disease than their heavier counterparts.

“Researchers should be looking at genetic and metabolic factors that define type 2 diabetes for those with different weights,” said Jerant. “Teasing out those factors could eventually enable us to develop and test diabetes management plans that address those differences.”

Jerant’s co-authors were Peter Franks and Klea Bertakis, professors of family and community medicine at UC Davis. They received no external funding for their research.

“Body Mass Index and Health Care Utilization in Diabetic and Nondiabetic Individuals” is available at http://journals.lww.com/lww-medicalcare/Abstract/publishahead/Body_Mass_Index_and_Health_Care_Utilization_in.99062.aspx.

“Body Mass Index and Health Status in Diabetic and Nondiabetic Individuals” is available at www.nature.com/nutd/journal/v5/n4/full/nutd20152a.html.

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Graduate student examines use of social media in health care

Post conveying negative emotions generate an increase in user comments, study finds.

Holly Rus, UC Merced

By James Leonard, UC Merced

The use of images and direct questions by health communicators on Facebook tends to increase user engagement, though linking to external websites and videos does not. Posts conveying positive emotions have no clear impact on engagement, while negative ones — including expressions of depression, sadness, doubt, fear, hopelessness, anxiety and anger — generate an increase in user comments.

Those were a few of the results of a study on social media and health communications by UC Merced Ph.D. student Holly Rus, who will present her findings this week during the 36th Annual Meeting & Scientific Sessions of the Society of Behavioral Medicine in San Antonio.

Working with professor Linda Cameron, Rus conducted an analysis of more than 500 posts by diabetes-related support pages on Facebook. The researchers looked for attributes in posts that could be used to predict not just overall user engagement, but specific types of engagement.

Among the study’s findings:

  • Posts with images had more than four times as many likes and 11 times as many shares as those without.
  • Messages of support or encouragement and posts soliciting input both had more than twice as many comments as those without.
  • Emotionally positive posts — including hope, optimism, humor, happiness, benefit finding and gratitude — did not predict any particular engagement, while negative ones generated a roughly threefold increase in comments.
  • Posts about the possible effects of diabetes generated more than twice as many shares as those without, while the use of external links predicted fewer likes and shares.

It’s clear that social media has the potential to be a significant resource for health communicators and for patients and their supporters. Rus said her study is a step toward a better understanding of how to make this growing form of health communication more effective.

“Ultimately we aimed to figure out which ingredients of online health messages were most likely to engage users,” she said. “Doing this will help us better understand if and how social media can best be used in health care.”

Rus’ study received special recognition from SBM, being chosen as a Citation Abstract and a Meritorious Student Abstract. An enlarged version of her abstract will be on display during one of the poster sessions at the San Antonio Marriott Rivercenter.

Cameron’s research focuses on health communications and psychosocial interventions for individuals who have or are at risk for illnesses like cancer, heart disease and diabetes. She’s part of a thriving group of UC Merced professors studying health psychology, a rapidly emerging field examining the interactions between behavior and physical health.

Cameron said this research could have significant implications in an area of ever-increasing importance.

“The big-picture question is how we can best harness social media to improve health care,” Cameron said. “Social media is a huge resource that people are increasingly using to gather health information. How can we shape these messages to increase engagement and encourage better health behaviors? If we want to be effective, we have to attract people to the message and have those people pass it around.”

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New clues to treat juvenile diabetes

Hartwell Foundation award winners include researchers from UC Davis, UC San Diego.

By Andy Fell, UC Davis

UC Davis assistant professor Mark Huising is a recipient of The Hartwell Foundation 2014 Individual Biomedical Research Award to support his early-stage research toward a cure for juvenile diabetes. Diabetes affects 10 percent of the entire United States population, including approximately a million children. Remarkably, 40 children every day receive the diagnosis of diabetes.

Huising, who works in the Department of Neurobiology, Physiology and Behavior at the UC Davis College of Biological Sciences, also holds an appointment in the Department of Physiology and Membrane Biology at the UC Davis School of Medicine. He joined UC Davis in November 2014 having previously worked at the Salk Institute in La Jolla. He is interested in how certain cells in the pancreas control the body’s response to sugar in diabetes. Achieving a balance between reduction of elevated blood sugar levels and the need to prevent potentially fatal low sugar levels is critical to maintaining health.

The Hartwell Foundation award will provide $300,000 in direct cost over three years to support Huising’s research looking at the biological signals and triggers affecting a small pool of cells in the pancreas that could be essential in regenerating control of blood sugar in this disease. The Individual Biomedical Research Award to Huising represents the ninth time a researcher from UC Davis has won such recognition from The Hartwell Foundation over the last seven years. The 12 Hartwell Foundation 2014 Individual Biomedical Research Award winners also include Shira Robbins, UC San Diego associate clinical professor of ophthalmology, for “Omega-3 Fatty Acids as a Therapy for the Prevention of Retinopathy of Prematurity.”

Islets, insulin and diabetes

Diabetes has been a prevalent health problem since ancient times. Two forms of the disease are known — Type 1, or “insulin-dependent” diabetes, and Type 2 diabetes, caused when the body fails to regulate the level of sugar properly, sending it either soaring high or dropping to very low levels.

In juvenile diabetes, the body’s own immune system causes damage to a specialized region in the pancreas, called the islets of Langerhans, effectively rejecting the tissue. The damage is significant because the beta cells within the islets make insulin. Normally, increasing blood sugar stimulates insulin production, which causes the body’s cells to pull sugar out of circulation. The islets also house alpha cells, which make another hormone, glucagon. When blood sugar falls, alpha cells make more glucagon, which causes the liver to break out stocks of glycogen and turn it into glucose.

New insight on insulin from immature cells

At diagnosis of diabetes, the body’s immune system has already destroyed most beta cells and any ability to produce insulin. The remaining alpha cells build up and release glucagon, which causes a serious side-effect of juvenile diabetes. The majority of scientific strategies focus on means to prevent beta cell death and promote beta cell division. However, efforts to restore lost beta cells have been largely unsuccessful.

Huising has discovered that, in laboratory mice, immature beta cells may spontaneously arise from alpha cells. He proposes to identify the biochemical signals that switch alpha cells into beta cells and determine in human tissue whether such beta cells are adequately mature and functional. Huising’s approach represents a shift in the current paradigm that after birth beta cells arise exclusively through the division of existing beta cells.

If successful, Huising will harness the intrinsic potential for beta cell regeneration that exists within pancreatic islets. This approach has the benefit of blocking a serious side effect of juvenile diabetes and represents a potential path to a cure for the disease.

Biomedical research that benefits children

“The Hartwell Foundation has a strong commitment to providing financial support to stimulate discovery in early-stage, innovative biomedical research that has potential to benefit children of the United States,” said Fred Dombrose, president of The Hartwell Foundation. “Mark Huising typifies the innovative, young investigator we seek to fund. We want to make a difference.”

Top Ten Center designation

In addition to the individual award, The Hartwell Foundation designated UC Davis as one of its Top Ten Centers for Biomedical Research for the fifth consecutive year.

In selecting each research center of excellence, The Hartwell Foundation takes into account the shared values the institution has with the foundation relating to children’s health, the presence of an associated medical school and biomedical engineering program, and the quality and scope of ongoing biomedical research.

The foundation also considers the institutional commitment to support collaboration, provide encouragement, and extend technical support to the investigator, especially as related to translational approaches and technology transfer that could promote rapid clinical application of research results.

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‘Open’ stem cell chromosomes reveal new possibilities for diabetes

UC San Diego researchers map chromosomal changes over time.

Pancreatic cells derived from embryonic stem cells.

By Heather Buschman, UC San Diego

Stem cells hold great promise for treating a number of diseases, in part because they have the unique ability to differentiate, specializing into any one of the hundreds of cell types that comprise the human body. Harnessing this potential, though, is difficult. In some cases, it takes up to seven carefully orchestrated steps of adding certain growth factors at specific times to coax stem cells into the desired cell type. Even then, cells of the intestine, liver and pancreas are notoriously difficult to produce from stem cells. Writing in Cell Stem Cell today (April 2), researchers at the UC San Diego School of Medicine have discovered why.

It turns out that the chromosomes in laboratory stem cells open slowly over time, in the same sequence that occurs during embryonic development. It isn’t until certain chromosomal regions have acquired the “open” state that they are able to respond to added growth factors and become liver or pancreatic cells. This new understanding, say researchers, will help spur advancements in stem cell research and the development of new cell therapies for diseases of the liver and pancreas, such as type 1 diabetes.

“Our ability to generate liver and pancreatic cells from stem cells has fallen behind the advances we’ve made for other cell types,” said Maike Sander, M.D., professor of pediatrics and cellular and molecular medicine and director of the Pediatric Diabetes Research Center at UC San Diego. “So we haven’t yet been able to do things like test new drugs on stem cell-derived liver and pancreatic cells. What we have learned is that if we want to make specific cells from stem cells, we need ways to predict how those cells and their chromosomes will respond to the growth factors.”

Sander led the study, together with co-senior author Bing Ren, Ph.D., professor of cellular and molecular medicine at UC San Diego and Ludwig Cancer Research member.

Chromosomes are the structures formed by tightly wound and packed DNA. Humans have 46 chromosomes – 23 inherited from each parent. Sander, Ren and their teams first made maps of chromosomal modifications over time, as embryonic stem cells differentiated through several different developmental intermediates on their way to becoming pancreatic and liver cells. Then, in analyzing these maps, they discovered links between the accessibility (openness) of certain regions of the chromosome and what they call developmental competence – the ability of the cell to respond to triggers like added growth factors.

“We’re also finding that these chromosomal regions that need to open before a stem cell can fully differentiate are linked to regions where there are variations in certain disease states,” Sander says.

In other words, if a person were to inherit a genetic variation in one of these chromosomal regions and his or her chromosome didn’t open up at exactly the right time, he or she could hypothetically be more susceptible to a disease affecting that cell type. Sander’s team is now working to further investigate what role, if any, these chromosomal regions and their variations play in diabetes.

Co-authors of this study also include Allen Wang, Ruiyu Xie, Thomas Harper, Nisha A. Patel, Kayla Muth, Jeffrey Palmer, Jinzhao Wang, and Dieter K. Lam, UC San Diego; Feng Yue, The Pennsylvania State University; Yan Li, Yunjiang Qiu, Ludwig Cancer Research; and Jeffrey C. Raum, Doris A. Stoffers, University of Pennsylvania.

This research was funded, in part, by the National Institutes of Health (grants U01-DK089567, U01-DK072473, U01-ES017166, U01-DK089540 and T32-DK7494-27), California Institute for Regenerative Medicine (grants RB5-07236 and TG2-01154, Bridges to Stem Cells Program), Helmsley Charitable Trust and JDRF.

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UC researchers awarded stem cell grants

Funding to develop treatments for Huntington’s, spina bifida, chronic diabetic wounds.

Roslyn Rivkah Isseroff, UC Davis

University of California researchers from two campuses received three grants totaling more than $12 million in funding from the state’s stem cell agency to develop stem cell treatments for Huntington’s disease, spina bifida and chronic diabetic wounds.

The funding was part of $25.2 million in Preclinical Development Awards targeting seven deadly or disabling disorders – what the California Institute for Regenerative Medicine considers “the most promising” research leading up to human clinical trials using stem cells to treat disease and injury.

UC Davis researchers were awarded a pair of grants totaling more than $7 million to develop stem cell therapies for spina bifida ($2.2 million) and chronic diabetic wounds ($5 million).

Diana Farmer, professor and chair of surgery at UC Davis Medical Center, is developing a placental stem cell therapy for spina bifida, the common and devastating birth defect that causes lifelong paralysis as well as bladder and bowel incontinence. She and her team are working on a unique treatment that can be applied in utero – before a baby is born — in order to reverse spinal cord damage.

Diana Farmer, UC Davis

Roslyn Rivkah Isseroff, a UC Davis professor of dermatology, and Jan Nolta, professor of internal medicine and director of the university’s Stem Cell Program, are developing a wound dressing containing stem cells that could be applied to chronic wounds and be a catalyst for rapid healing. This is Isseroff’s second CIRM grant, and it will help move her research closer to having a product approved by the U.S. Food and Drug Administration that specifically targets diabetic foot ulcers, a condition affecting more than 6 million people in the country.

Also, Leslie Thompson of the Sue & Bill Gross Stem Cell Research Center at UC Irvine has been awarded $5 million to continue her CIRM-funded effort to develop stem cell treatments for Huntington’s disease. The grant supports her next step: identifying and testing stem cell-based treatments for HD, an inherited, incurable and fatal neurodegenerative disorder. In this project, Thompson and her colleagues will create an HD therapy employing human embryonic stem cells that can be evaluated in clinical trials.

Leslie Thompson, UC Irvine

CIRM’s governing board also approved an application for the Tools and Technology Award that had been deferred from the January meeting. UCLA’s Carla Koehler will now get $1.3 million for research on a small molecule tool for reducing the malignant potential in reprogramming human induced pluripotent stem cells and embryonic stem cells.

Overall, CIRM’s governing board has awarded nearly $1.9 billion in stem cell grants, with half of the total going to the University of California or UC-affiliated institutions.

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Necklace and smartphone app can help people track food intake

UCLA-developed app could help battle obesity, heart disease and diabetes.

WearSens rests loosely above the sternum and uses highly sensitive sensors to capture vibrations from the action of swallowing.

By Bill Kisliuk, UCLA

A sophisticated necklace developed by researchers at the UCLA Henry Samueli School of Engineering and Applied Science can monitor food and drink intake, which could help wearers track and improve their dietary habits.

The inventors of the WearSens device say it could help battle obesity, heart disease, diabetes and other problems related to nutrition.

Majid Sarrafzadeh, a distinguished professor of computer science and co-director of UCLA’s Wireless Health Institute, led a team that created the device and an algorithm that translates data from the necklace, and tested it on 30 people who ate a variety of foods.

The researchers found that WearSens can differentiate between solids and liquids with 87 percent accuracy, between hot drinks and room-temperature drinks with 90 percent accuracy, and between food items with different textures with 80 percent accuracy. Researchers say those figures will improve as users calibrate the device based on their eating habits.

The research was published online by the IEEE Sensors Journal.

“Today, many people try to track their food intake with journals, but this is often not effective or convenient,” Sarrafzadeh said. “This technology allows individuals and health care professionals to monitor intake with greater accuracy and more immediacy.”

WearSens rests loosely above the sternum and uses highly sensitive piezoelectric sensors to capture vibrations from the action of swallowing. Piezoelectric sensors produce voltage based on the mechanical stress — or movement or pressure — that is applied to them.

When the wearer eats or drinks, skin and muscle motion from the lower trachea trigger the sensors, and the necklace transmits the signals to a smartphone, where the UCLA-developed algorithm converts the data into information about the food or beverage. The phone displays data about the volume of food or liquid consumed and can offer advice or analysis; for example, that the wearer is eating more than in previous days or that the person should drink more water.

With the WearSens device, the sensor information is translated using a spectrogram, which offers a visual representation of vibrations picked up by the sensors. Spectrograms are often used in speech therapy and seismology, among other applications.

“The breakthroughs are in the design of the necklace, which is simple and does not interfere with daily activity, and in identifying statistical measures that distinguish food intake based on spectrogram images generated from piezoelectric sensor signals,” said Nabil Alshurafa, a graduate student researcher at UCLA who is a co-inventor of the device and the first author of the research.

The study’s other authors are co-inventor Haik Kalantarian, a graduate student researcher; Shruti Sarin and Behnam Shahbazi, also graduate student researchers; Jason Liu, who was a UCLA graduate student at the time he worked on the research; and postdoctoral researcher Mohammad Pourhomayoun.

The team is continuing to refine the algorithms and the necklace’s design. The researchers hope WearSens will be available to the public later this year.

The technology is available for licensing via the UCLA Office of Intellectual Property and Industry-Sponsored Research, which facilitates the conversion of UCLA research to benefit the public.

The research was supported by the National Science Foundation.

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Forging ahead in fight against hemochromatosis

Research advances are improving prognosis for hereditary blood-iron overload disorder.

By Tom Vasich, UC Irvine

Since coming to the UC Irvine School of Medicine in 1998, Christine and Gordon McLaren have been leading the way in the research and treatment of hemochromatosis, a hereditary disease that causes the body to absorb too much iron from ingested food.

The excess iron is stored in various organs – especially the liver, heart and pancreas – and can poison them, precipitating such life-threatening conditions as cirrhosis and liver cancer, heart arrhythmias and diabetes. Once considered a rare disease, hemochromatosis is now recognized as one of the most common inherited disorders, affecting as many as 1 million people in the U.S.

Christine McLaren is a professor of epidemiology, and Dr. Gordon McLaren is a professor of medicine specializing in hematology and oncology who practices in the Veterans Affairs Long Beach Healthcare System.

Over the past few months, the wife and husband have made noteworthy strides: Last September, they received a $2 million grant from the National Institute of Diabetes & Digestive & Kidney Diseases to investigate the genetic modifiers of iron status in hemochromatosis. And a study the McLarens presented in December at the annual meeting of the American Society of Hematology was a “Best of ASH” honoree.

Here, they discuss their work:

How did you both acquire an interest in this field?

Christine: We developed a focus on the disorder independently. Early in my career, I provided statistical consulting for hematologists who had research projects involving iron overload and iron deficiency. Meanwhile, Gordon has had a long-standing interest for over 30 years in the area of iron metabolism, with an emphasis on hemochromatosis.

In 2000, after Gordon and I had joined the faculty at UCI, we were fortunate to receive National Institutes of Health funding to work together and to screen more than 20,000 primary care patients for iron overload and hereditary hemochromatosis at UCI ambulatory care clinics.

The primary goal of that research was to contribute to a national epidemiologic study of iron overload and hereditary hemochromatosis in a multicenter, multiethnic, primary care-based sample of over 100,000 people.

How are people susceptible to hemochromatosis?

Gordon: Generally, iron overload occurs only in people with two copies of the hemochromatosis gene (one copy inherited from each parent). The frequency of having two copies in the European-American population is about 5 per 1,000 persons.

However, not all people with two copies of the gene will develop iron overload. Thus, we think there must be other factors – such as mutations in other genes affecting dietary iron absorption – that are required for the disease to become fully manifest, and this is what we’re studying.

If we can identify what causes the difference, we may be able to use this information to predict which patients are at greater risk of developing iron overload and when to begin therapy to remove excess iron before it accumulates to toxic levels.

Interestingly, the frequency of the genetic predisposition to hemochromatosis among European-Americans is the same in men and women, but for reasons that are not completely understood, men are more likely to develop the full-blown syndrome.

What do you plan to accomplish with the $2 million in support from the National Institute of Diabetes & Digestive & Kidney Diseases?

Gordon: We’re leading a multidisciplinary team of investigators at eight research institutions in the U.S., Canada and Australia. To better understand the reasons for this variability in disease expression, our group will examine genetic factors in the susceptibility or resistance to iron overload in patients with a genetic predisposition for hemochromatosis across a wide range of geographic areas.

The purpose of this research is to identify other inherited traits that may interact to cause more severe disease in certain patients. It’s important to identify persons at risk because effective iron removal treatment is available, and beginning such therapy before iron overload becomes advanced can prevent disease complications.

Christine: This work can have important clinical applications, including the ability to identify young hemochromatosis patients at risk for potentially severe iron overload later in life, thereby influencing physicians’ recommendations for iron removal therapy and long-term follow-up. We’re hopeful that our findings will lead to new approaches that will inform the development of innovative prevention and treatment strategies tailored to the individual.

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Pens filled with high-tech inks for do-it-yourself sensors

New simple tool is opening door to where anyone will be able to build sensors, anywhere.

By Ioana Patringenaru, UC San Diego

A new simple tool developed by nanoengineers at the University of California, San Diego, is opening the door to an era when anyone will be able to build sensors, anywhere, including physicians in the clinic, patients in their home and soldiers in the field.

The team from the University of California, San Diego, developed high-tech bio-inks that react with several chemicals, including glucose. They filled off-the-shelf ballpoint pens with the inks and were able to draw sensors to measure glucose directly on the skin and sensors to measure pollution on leaves.

Skin and leaves aren’t the only media on which the pens could be used. Researchers envision sensors drawn directly on smart phones for personalized and inexpensive health monitoring or on external building walls for monitoring of toxic gas pollutants. The sensors also could be used on the battlefield to detect explosives and nerve agents.

The team, led by Joseph Wang, the chairman of the Department of NanoEngineering at the University of California, San Diego, published their findings in the Feb. 26 issue of Advanced Healthcare Materials. Wang also directs the Center for Wearable Sensors at UC San Diego.

“Our new biocatalytic pen technology, based on novel enzymatic inks, holds considerable promise for a broad range of applications on site and in the field,” Wang said.

The biggest challenge the researchers faced was making inks from chemicals and biochemicals that aren’t harmful to humans or plants; could function as the sensors’ electrodes; and retain their properties over long periods in storage and in various conditions. Researchers turned to biocompatible polyethylene glycol, which is used in several drug delivery applications, as a binder. To make the inks conductive to electric current they used graphite powder. They also added chitosan, an antibacterial agent which is used in bandages to reduce bleeding, to make sure the ink adhered to any surfaces it was used on. The inks’ recipe also includes xylitol, a sugar substitute, which helps stabilize enzymes that react with several chemicals the do-it-yourself sensors are designed to monitor.

Reusable glucose sensors

Wang’s team has been investigating how to make glucose testing for diabetics easier for several years. The same team of engineers recently developed non-invasive glucose sensors in the form of temporary tattoos. In this study, they used pens, loaded with an ink that reacts to glucose, to draw reusable glucose-measuring sensors on a pattern printed on a transparent, flexible material which includes an electrode. Researchers then pricked a subject’s finger and put the blood sample on the sensor. The enzymatic ink reacted with glucose and the electrode recorded the measurement, which was transmitted to a glucose-measuring device. Researchers then wiped the pattern clean and drew on it again to take another measurement after the subject had eaten.

Researchers estimate that one pen contains enough ink to draw the equivalent of 500 high-fidelity glucose sensor strips. Nanoengineers also demonstrated that the sensors could be drawn directly on the skin and that they could communicate with a Bluetooth-enabled electronic device that controls electrodes called a potentiostat, to gather data.

Sensors for pollution and security

The pens would also allow users to draw sensors that detect pollutants and potentially harmful chemicals sensors on the spot. Researchers demonstrated that this was possible by drawing a sensor on a leaf with an ink loaded with enzymes that react with phenol, an industrial chemical, which can also be found in cosmetics, including sunscreen. The leaf was then dipped in a solution of water and phenol and the sensor was connected to a pollution detector. The sensors could be modified to react with many pollutants, including heavy metals or pesticides.

Next steps include connecting the sensors wirelessly to monitoring devices and investigating how the sensors perform in difficult conditions, including extreme temperatures, varying humidity and extended exposure to sunlight.

“Biocompatible Enzymatic Roller Pens for Direct Writing of Biocatalytic Materials: ‘Do-it-yourself’ Electrochemical Biosensors” is authored by Amay J. Bandodkar, Wenzhao Jia, Julian Ramirez and Wang.

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Molecular link between obesity, type 2 diabetes reveals potential therapy

UC San Diego researchers find that inflammatory molecule LTB4 promotes insulin resistance.

By Heather Buschman, UC San Diego

Obesity causes inflammation, which can in turn lead to type 2 diabetes. What isn’t well established is how inflammation causes diabetes — or what we can do to stop it. Researchers at the UC San Diego School of Medicine have discovered that the inflammatory molecule LTB4 promotes insulin resistance, a first step in developing type 2 diabetes. What’s more, the team found that genetically removing the cell receptor that responds to LTB4, or blocking it with a drug, improves insulin sensitivity in obese mice. The study is published today (Feb. 23) by Nature Medicine.

“This study is important because it reveals a root cause of type 2 diabetes,” said Jerrold M. Olefsky, M.D., professor of medicine, associate dean for scientific affairs and senior author of the study. “And now that we understand that LTB4 is the inflammatory factor causing insulin resistance, we can inhibit it to break the link between obesity and diabetes.”

Here’s what’s happening in obesity, according to Olefsky’s study. Extra fat, particularly in the liver, activates resident macrophages, the immune cells living there. These macrophages then do what they’re supposed to do when activated — release LTB4 and other immune signaling molecules to call up an influx of new macrophages. Then, in a positive feedback loop, the newly arriving macrophages also get activated and release even more LTB4 in the liver.

This inflammatory response would be a good thing if the body was fighting off an infection. But when inflammation is chronic, as is the case in obesity, all of this extra LTB4 starts activating other cells, too. Like macrophages, nearby liver, fat and muscle cells also have LTB4 receptors on their cell surfaces and are activated when LTB4 binds them. Now, in obesity, those cells become inflamed as well, rendering them resistant to insulin.

Once Olefsky and his team had established this mechanism in their obese mouse models, they looked for ways to inhibit it. First, they genetically engineered mice that lack the LBT4 receptor. When that approach dramatically improved the metabolic health of obese mice, they also tried blocking the receptor with a small molecule inhibitor. This particular compound was at one time being tested in clinical trials, but was dropped when it didn’t prove all that effective in treating its intended ailment. Olefsky’s team fed the prototype drug to their mice and found that it worked just as well as genetic deletion at preventing — and reversing — insulin resistance.

“When we disrupted the LTB4-induced inflammation cycle either through genetics or a drug, it had a beautiful effect — we saw improved metabolism and insulin sensitivity in our mice,” Olefsky said. “Even though they were still obese, they were in much better shape.”

Co-authors of this study include Pingping Li, Da Young Oh, Gautam Bandyopadhyay, William S. Lagakos, Saswata Talukdar, Olivia Osborn, Andrew Johnson, Heekyung Chung, Rafael Mayoral, Michael Maris, Jachelle M Ofrecio, Sayaka Taguchi, Min Lu, all at UC San Diego.

This research was funded, in part, by the National Institute of Diabetes and Digestive and Kidney Diseases (DK033651, DK074868, DK063491, DK09062), the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Merck Inc.

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Tobacco-smoking parents increase diabetes risk for children exposed in utero

“Smoking of parents is by itself a risk factor for diabetes, independent of obesity or birth weight.”

Credit: iStock

By Michele La Merrill and Kat Kerlin, UC Davis

Children exposed to tobacco smoke from their parents while in the womb are predisposed to developing diabetes as adults, according to a study from the University of California, Davis, and the Berkeley nonprofit Public Health Institute.

In the study, published today (Feb. 9) in the Journal of Developmental Origins of Health and Disease, women whose mothers smoked while pregnant were two to three times as likely to be diabetic as adults. Dads who smoked while their daughter was in utero also contributed to an increased diabetes risk for their child, but more research is needed to establish the extent of that risk.

“Our findings are consistent with the idea that gestational environmental chemical exposures can contribute to the development of health and disease,” said lead author Michele La Merrill, an assistant professor of environmental toxicology at UC Davis.

The study analyzed data from 1,800 daughters of women who had participated in the Child Health and Development Studies, an ongoing project of the Public Health Institute. The CHDS recruited women who sought obstetric care through Kaiser Permanente Foundation Health Plan in the San Francisco Bay Area between 1959 and 1967. The data was originally collected by PHI to study early risk of breast cancer, which is why sons were not considered in this current study.

In previous studies, fetal exposure to cigarette smoke has also been linked to higher rates of obesity and low birth weight. This study found that birth weight did not affect whether the daughters of smoking parents developed diabetes.

“We found that smoking of parents is by itself a risk factor for diabetes, independent of obesity or birth weight,” said La Merrill. “If a parent smokes, you’re not protected from diabetes just because you’re lean.”

The study was supported through funding from the National Institute of Environmental Health Sciences, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the California Breast Cancer Research Program Special Research Initiative.

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