TAG: "Diabetes"

Patient-centered research projects receive funding


UC Berkeley, UC Davis among recipients.

Heather Young, UC Davis

Two University of California research projects have been approved for funding in the latest round of awards by the Patient-Centered Outcomes Research Institute (PCORI).

A research project led by the Betty Irene Moore School of Nursing at UC Davis was approved for a $2.1 million award to study improving health for individuals with diabetes. Associate Vice Chancellor for Nursing and Dean Heather M. Young will lead the research project at UC Davis. The study will focus on individuals with diabetes and determine if innovative approaches, including mobile technology and nurse coaching, help those people better manage the chronic disease.

Young noted that researchers from other centers and organizations — including the UC Center for Information Technology Research for the Improvement of Society (CITRIS), the UC Davis Clinical Translational Science Center and the Initiative for Wireless Health and Wellness at UC Davis — contributed to foundational research for this study and will play important roles in completing this three-year project.

Stephen Shortell, UC Berkeley

Also, a research project led by UC Berkeley was approved for a $2.1 million award to study the delivery of care to patients with diabetes and cardiovascular diseases. Stephen Shortell, Blue Cross of California Distinguished Professor of Health Policy and Management and dean emeritus at the School of Public Health, will lead the research project at UC Berkeley. The study will see whether patients with diabetes or cardiovascular diseases who receive care from practices that more fully involve their patients have better clinical outcomes and satisfaction with their care than those that do not.

The studies are two of 33 proposals PCORI approved for $54.8 million in funding this week to advance the field of patient-centered comparative effectiveness research and provide patients, health care providers, and other clinical decision makers with information that will help them make better-informed choices.

Earlier this year, the National Institutes of Health and PCORI joined together to support a clinical trial to test individually tailored interventions to prevent fall-related injuries. That award, made by the NIH’s National Institute on Aging and funded by PCORI as part of the two organizations’ Falls Injuries Prevention Partnership, is expected to total $30 million over the five-year project.

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Low-income diabetics up to 10 times likelier to lose a limb than wealthier patients


Most amputations preventable with earlier medical care, UCLA researchers say.

Carl Stevens, UCLA

It’s no secret that poverty is bad for your health. Now a new UCLA study demonstrates that California diabetics who live in low-income neighborhoods are up to 10 times more likely to lose a toe, foot or leg than patients residing in more affluent areas of the state. Earlier diagnosis and proper treatment could prevent many of these amputations, the researchers say.

The study authors hope their findings, published in the August issue of Health Affairs, will motivate public agencies and medical providers to reach out to patients at risk of late intervention and inspire policymakers to adopt legislation to reduce barriers to care.

“I’ve stood at the bedsides of diabetic patients and listened to the surgical residents say, ‘We have to cut your foot off to save your life,’” said lead author Dr. Carl Stevens, a clinical professor of medicine at the David Geffen School of Medicine at UCLA. “These patients are often the family breadwinners and parents of young children — people with many productive years ahead of them.

“When you have diabetes, where you live directly relates to whether you’ll lose a limb to the disease,” added Stevens, an emergency physician for 30 years at Harbor–UCLA Medical Center. ”Millions of Californians have undergone preventable amputations due to poorly managed diabetes. We hope our findings spur policymakers nationwide to improve access to treatment by expanding Medicaid and other programs targeting low-income residents, as we did in California in 2014.”

Dylan Roby, UCLA

The authors used data from the UCLA Center for Health Policy Research’s California Health Interview Survey, which estimated the prevalence of diabetes among low-income populations by ZIP code. They blended these statistics with household-income figures from the U.S. Census Bureau and hospital discharge data from the Office of Statewide Health Planning and Development that tracked diabetes-related amputations by ZIP code.

The result was a detailed set of maps showing diabetic amputation rates by neighborhood for patients 45 and older — the age range at greatest risk for amputation from disease complications.

“Neighborhoods with high amputation rates clustered geographically into hot spots with a greater concentration of households falling below the federal poverty level,” said co-author Dylan Roby, director of health economics at the UCLA Center for Health Policy Research and an assistant professor at the UCLA Fielding School of Public Health. “Amputation rates in California were 10 times higher in the poorest neighborhoods, like Compton and East Los Angeles, than in the richest neighborhoods, such as Malibu and Beverly Hills.”

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DDT linked to slow metabolism, obesity and diabetes


Study shows developmental exposure to DDT can affect female offspring.

Exposure of pregnant mice to the pesticide DDT is linked to an increased risk of obesity, diabetes, high cholesterol and related conditions in female offspring later in life, according to a study led by the University of California, Davis.

The study, published online today (July 30) in the journal PLOS ONE, is the first to show that developmental exposure to DDT increases the risk of females later developing metabolic syndrome — a cluster of conditions that include increased body fat, blood glucose and cholesterol.

DDT was banned in the United States in the 1970s but continues to be used for malaria control in countries including India and South Africa.

Scientists gave mice doses of DDT comparable to exposures of people living in malaria-infested regions where it is regularly sprayed, as well as of pregnant mothers of U.S. adults who are now in their 50s.

“The women and men this study is most applicable to in the United States are currently at the age when they’re more likely to develop metabolic syndrome, because these are diseases of middle- to late adulthood,” said lead author Michele La Merrill, assistant professor of environmental toxicology at UC Davis.

The scientists found that exposure to DDT before birth slowed the metabolism of female mice and lowered their tolerance of cold temperature. This increased their likelihood of developing metabolic syndrome and its host of related conditions.

“As mammals, we have to regulate our body temperature in order to live,” La Merrill said. “We found that DDT reduced female mice’s ability to generate heat. If you’re not generating as much heat as the next guy, instead of burning calories, you’re storing them.”

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Mechanism that clears excess of pancreatic protein linked with Type 2 diabetes


Autophagy appears to not work properly, contributing to destruction of insulin-producing beta cells.

People with Type 2 diabetes have an excess of a protein called islet amyloid polypeptide, or IAPP, and the accumulation of this protein is linked to the loss of insulin-producing pancreatic beta cells.

What causes this accumulation of IAPP in pancreatic beta cells of people with diabetes has remained a mystery. But a team of researchers from the Larry L. Hillblom Islet Research Center led by Dr. Peter Butler, professor of medicine at UCLA, may have found an answer in autophagy, a process that clears damaged and toxic proteins from cell.

In a study published online July 18 in the peer-reviewed Journal of Clinical Investigation, the UCLA researchers suggest that, in people who do not have Type 2 diabetes, autophagy prevents the accumulation of toxic forms of IAPP. In people with Type 2 diabetes, the process appears to not work properly, contributing to the destruction of beta cells. As the body’s insulin producers, beta cells play a key role in maintaining healthy blood sugar levels.

“Only a few previous studies have reported that autophagy is important for beta cell function and survival,” said Safia Costes, a research scientist at the Hillblom Center and the study’s co-first author. “Those studies, however, were not conducted to address the role of this process in the regulation of the amyloidogenic protein, which is an important contributor to Type 2 diabetes.”

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New compound treats both blindness and diabetes in animal studies


UCSF-led study offers fresh insights into role of cellular stress in degenerative illnesses.

In a new study led by UC San Francisco scientists, a chemical compound designed to precisely target part of a crucial cellular quality-control network provided significant protection, in rats and mice, against degenerative forms of blindness and diabetes.

In addition to opening a promising drug-development path for the wide range of diseases caused by cell loss, the new research offers a new view of the workings of the unfolded protein response (UPR), a cellular “life-or-death” signaling network: When cells are under stress, the UPR works to ensure that they produce properly configured proteins, but those cells not up to this task are quickly prompted by the UPR to self-destruct.

A component of the UPR known as the IRE1 pathway has generally been thought to handle the protective aspects of this response, promoting cell survival by providing cells with the biological resources they need to cope with stress, while a complementary pathway, called PERK, has been associated with cell death.

But in the new research, published in today’s (July 10) edition of Cell, when researchers used KIRA6, a small-molecule kinase inhibitor they designed to inhibit the actions of IRE1α — the molecular sensor that triggers the IRE1 pathway — they blocked cell death and preserved function in experimental models of two human diseases.

In two rat models of retinitis pigmentosa, a disease in which light-sensing cells in the eye progressively die off, causing blindness, KIRA6 preserved both the number of these cells and visual function. And in mice from a strain known as Akita, which carry a genetic mutation that causes diabetes in early life as stressed insulin-producing beta cells of the pancreas degenerate, KIRA6 protected beta cells from cell death, leading to a twofold increase in insulin production and improving blood glucose control.

“This is a huge advance in our field,” said co-senior author Scott A. Oakes, M.D., associate professor of pathology at UCSF. “On the surface these would seem to be two very different diseases, but IRE1-induced cell death is at the root of both of them.”

The results are the culmination of “a gigantic project,” first to establish that the IRE1 pathway could drive degenerative disease, and then to design and test compounds to head off the damage, said UCSF’s Feroz Papa, M.D., Ph.D., associate professor of medicine and co-senior author, and a member of the California Institute for Quantitative Biosciences. “It took four years, over a hundred separate experiments in various contexts — not counting replications — and involved 24 researchers working in seven labs across four cities.”

KIRA6 is the latest in a series of compounds (the acronym stands for “Kinase-Inhibiting RNase Attenuators”) that were originally designed and synthesized in the labs of study co-authors Dustin J. Maly, Ph.D., associate professor of chemistry at The University of Washington, Seattle, and Bradley J. Backes, Ph.D., associate professor of medicine at UCSF.

“While KIRA6 showed efficacy in animals,” said Papa, “it is important to stress that more optimization through medicinal chemistry efforts is needed to develop this class of compounds to the stage where they could be tested for efficacy in humans through clinical trials.”

Oakes and Papa said that support from the Cleveland, Ohio-based Harrington Discovery Institute was crucial to sustaining this complex collaboration. Both scientists were 2013 winners of Scholar-Innovator Awards from the institute, which is part of The Harrington Project for Development and Discovery a $250 million national model to accelerate the development of medical breakthroughs by physician-scientists into medicines that benefit patients. Other critical support for the work came from the National Institutes of Health, the Juvenile Diabetes Research Foundation, the Burroughs Wellcome Fund, the American Cancer Society and the Howard Hughes Medical Institute.

Other UCSF researchers on the project included Douglas B. Gould, Ph.D., associate professor of ophthalmology; Michael German, M.D., professor of medicine; postdoctoral fellows Rajarshi Ghosh, Ph.D., and Likun Wang, Ph.D., and graduate student Eric S. Wang, all co-first authors; postdoctoral fellows Aeid Igbaria, Ph.D., Shuhei Morita, M.D., Ph.D., Kris Prado, M.D., Maike Thamsen, Ph.D., Hector Macias, Ph.D., and Marcel V. Alavi, Ph.D.; former research associate Deborah Caswell; graduate student Kurt F. Weiberth; and research associate Micah J. Gliedt. The team was also joined by other colleagues from The University of Washington, Seattle; The Miller School of Medicine at The University of Miami, Florida; and the Albert Einstein College of Medicine, in Bronx, New York.

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The connection between oxygen and diabetes


A lack of oxygen in fat cells triggers inflammation and insulin resistance in obesity.

Researchers at the UC San Diego School of Medicine have, for the first time, described the sequence of early cellular responses to a high-fat diet, one that can result in obesity-induced insulin resistance and diabetes. The findings, published in today’s (June 5) issue of Cell, also suggest potential molecular targets for preventing or reversing the process.

“We’ve described the etiology of obesity-related diabetes. We’ve pinpointed the steps, the way the whole thing happens,” said Jerrold M. Olefsky, M.D., associate dean for scientific affairs and Distinguished Professor of Medicine at UC San Diego. “The research is in mice, but the evidence suggests that the processes are comparable in humans, and these findings are important to not just understanding how diabetes begins, but how better to treat and prevent it.”

More than 25 million Americans have diabetes – 8.3 percent of the population – with another 79 million Americans estimated to be pre-diabetic, according to the American Diabetes Association. Diabetes is characterized by high blood sugar levels poorly regulated by either inadequate insulin production or because cells to not respond properly to the regulating hormone. Diabetes is the seventh-leading cause of death in the United States and a major risk factor for other life-threatening conditions, including heart disease and stroke.

Past research by Olefsky and others has shown that obesity is characterized by low-grade inflammation in adipose or fat tissues and that this inflammatory state can become chronic and result in systemic insulin resistance and diabetes. In today’s Cell paper, the scientists describe the earliest stages of the process, which begins even before obesity becomes manifest.

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Poor health, lifestyle factors linked to memory complaints


Early complaints often precursors to significant decline in later life, UCLA/Gallup study says.

Gary Small, UCLA

If you’re depressed, don’t get enough exercise or have high blood pressure, you may find yourself complaining more about memory problems, even if you’re a young adult, according to a new UCLA study.

UCLA researchers and the Gallup organization polled more than 18,000 people about their memory and a variety of lifestyle and health factors previously shown to increase the risk of Alzheimer’s disease and dementia. They found that many of these risk factors increased the likelihood of self-perceived memory complaints across all adult age groups.

The findings, published in today’s (June 4) edition of the journal PLOS ONE, may help scientists better identify how early lifestyle and health choices impact memory later in life. Examining these potential relationships, researchers say, could also help to pinpoint interventions aimed at lowering the risk of memory issues.

The 18,552 individuals polled ranged in age from 18 to 99. The known risk factors the researchers focused on included depression, lower education levels, physical inactivity, high blood pressure, diabetes, obesity and smoking. They were surprised by the prevalence of memory issues among younger adults, said the study’s senior author, Dr. Gary Small, UCLA’s Parlow–Solomon Professor on Aging and director of the UCLA Longevity Center.

“In this study, for the first time, we determined these risk factors may also be indicative of early memory complaints, which are often precursors to more significant memory decline later in life,” said Small, who is also a professor of psychiatry and biobehavioral sciences at the Semel Institute for Neuroscience and Human Behavior at UCLA.

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Study suggests depression, early death among seniors with disabilities linked


Depressed people less likely to adhere to prescribed medications, diet, exercise.

Carol Mangione, UCLA

People with diabetes have about double the risk of premature death as people of the same age without diabetes. Studies also have shown that they have about twice the odds of suffering from depression, which further increases their mortality risk.

A new UCLA-led study published in the Journal of the American Geriatrics Society found that among adults 65 and older with diabetes, depression is linked with a far greater chance for early death compared with people of the same age who do not have depression.

The researchers suggest that the higher mortality rate among those with depression could stem from the fact that depressed people are less likely than their non-depressed counterparts to adhere to their prescribed medications, diet, exercise and glucose self-monitoring.

The link between depression and mortality among people with diabetes has been the subject of many other studies, but this is the first to specifically compare the phenomenon as it affects those 65 and older with how it affects younger people, said Lindsay Kimbro, project director in the division of general internal medicine and health services research at the David Geffen School of Medicine at UCLA, and the study’s lead author.

Each participant was given a baseline survey and was contacted for a follow-up survey six to seven years after the initial interview.

“We found that depression mainly increases the risk of mortality among older persons with diabetes,” she said. “Although depression is an important clinical problem for people of all ages, when you split the different age groups, depression in the younger group doesn’t lead to increased mortality six to seven years later.”

A significant number of previous reports have linked diabetes and depression with an increased risk for premature death, but Kimbro said it now appears that those results may have been influenced by a focus on elderly patients.

The researchers analyzed information on 3,341 people with diabetes. Their data came from Translating Research Into Action for Diabetes, a study that collected health insurance claims, medical chart review, and phone interviews from 10 health plans in eight states.

The UCLA-led team reviewed information for patients 65 and older (1,402 people) and those who were 18 to 64 (1,939 participants), and measured mortality risk as the number of days until death since the time of the interview. The researchers controlled for age, gender, race and ethnicity, income, and co-morbidities such as heart and kidney disease associated with diabetes.

As in previous studies, the results revealed that the risk for early death among depressed people with diabetes was 49 percent higher than among those without depression. However, the correlation was even more pronounced among older adults: Researchers found a 78 percent higher mortality risk among those 65 and older than they did among non-depressed people with diabetes within that age group. For the younger participants with diabetes, the effect of depression on their risk for early death was not statistically significant.

“Our findings highlight the importance of screening for depression among older adults with diabetes, and of encouraging treatment for those who screen positive,” said Dr. Carol Mangione, a study co-author who holds the Geffen School’s Barbara A. Levey, M.D., and Gerald S. Levey, M.D., endowed chair.

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Pain killers may improve health of diabetics and the obese


Blocking pain receptor may improve lifespan, metabolic health.

Chili peppers

Blocking a pain receptor in mice not only extends their lifespan, it also gives them a more youthful metabolism, including an improved insulin response that allows them to deal better with high blood sugar.

“We think that blocking this pain receptor and pathway could be very, very useful not only for relieving pain, but for improving lifespan and metabolic health, and in particular for treating diabetes and obesity in humans,” said Andrew Dillin, a professor of molecular and cell biology at the University of California, Berkeley, and senior author of a new paper describing these results. “As humans age they report a higher incidence of pain, suggesting that pain might drive the aging process.”

The “hot” compound in chili peppers, capsaicin, is already known to activate this pain receptor, called TRPV1 (transient receptor potential cation channel subfamily V member 1). In fact, TRPV1 is often called the capsaicin receptor. Constant activation of the receptor on a nerve cell results in death of the neuron, mimicking loss of TRPV1, which could explain why diets rich in capsaicin have been linked to a lower incidence of diabetes and metabolic problems in humans.

More relevant therapeutically, however, is an anti-migraine drug already on the market that inhibits a protein called CGRP that is triggered by TRPV1, producing an effect similar to that caused by blocking TRPV1. Dillin showed that giving this drug to older mice restored their metabolic health to that of younger mice.

“Our findings suggest that pharmacological manipulation of TRPV1 and CGRP may improve metabolic health and longevity,” said Dillin, who is a Howard Hughes Medical Institute investigator and the Thomas and Stacey Siebel Distinguished Chair in Stem Cell Research. “Alternatively, chronic ingestion of compounds that affect TRPV1 might help prevent metabolic decline with age and lead to increased longevity in humans.”

Dillin and his colleagues at UC Berkeley and The Salk Institute for Biological Studies in La Jolla will publish their results in the May 22 issue of the journal Cell.

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Solution to helping teens with chronic disease may be at fingertips


Study shows technology improves transition into adulthood for teens with chronic disease.

Adolescents with chronic diseases (ACD), such as cystic fibrosis, gastrointestinal disorders (including Crohn’s disease) and Type 1 diabetes, often find the transition of managing their health care needs into adulthood to be challenging. Preparations for this transition are often clinic-based, costly and do not fully or effectively engage with this patient population. A new study by researchers at the UC San Diego School of Medicine found the answer to developing independent, self-management skills in ACD could be right at the patient’s fingertips.

The study is published in the June issue of Pediatrics.

Eighty-one patients, ranging from 12-to-20-years-old, participated in the eight-month study. Those assigned to the intervention group received an Internet and mobile phone system. Patients were asked to use a secure website weekly to receive theme-based materials and lifestyle tips. Automated text messages were also sent three to five times a week to help patients perform a variety of tasks, such as monitoring symptoms, keeping appointments and interpreting medical bills.

“Parents usually take a leading role when treating adolescents with chronic disease, but we want teenage patients to have a voice and become advocates for their own health,” said principal investigator Jeannie Huang, M.D., with the Department of Pediatrics at UC San Diego School of Medicine and Rady Children’s Hospital-San Diego. “The goal of the program is ultimately to improve communications between affected teens and their doctors.”

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Diabetes linked to a third of state’s hospitalizations


UCLA study highlights impact the disease is having on California’s health care costs.

Patients with diabetes account for one in three hospitalizations in California, according to a comprehensive new study on the prevalence of diabetes in hospitals and its impact on providers and spiraling health care costs.

The study of hospital discharge records, conducted by the UCLA Center for Health Policy Research with support from the California Center for Public Health Advocacy, found that among all hospitalized California patients aged 35 or older — the age group that accounts for most hospitalizations — 31 percent had diabetes.

Although diabetes may not be the initial reason for these hospitalizations, the disproportionate share of patients with diabetes highlights the impact this disease is having on California’s health care costs.

The research also showcases the percent of hospitalizations of patients with diabetes and related costs by county.

“If you have diabetes, you are more likely to be hospitalized, and your stay will cost more,” said Ying-Ying Meng, lead author of the study and a researcher at the UCLA Center for Health Policy Research. “There is now overwhelming evidence to show that diabetes is devastating not just to patients and families but to the whole health care system.”

Diabetes is one of the nation’s fastest-growing diseases and one of the most costly. It adds an extra $1.6 billion every year to hospitalization costs in California, with hospital stays for patients with diabetes costing nearly $2,200 more than stays for non-diabetic patients, according to the study. Three-quarters of that care is paid through Medicare and Medi-Cal, the study authors found, including $254 million in costs that are paid by Medi-Cal alone.

The disease is responsible for a long list of complications, including blindness, kidney disease, cardiovascular disease, amputations and premature death. Since 1980, diabetes cases have more than tripled nationally to 20.9 million. In California alone, diabetes cases have increased by 35 percent in 10 years.

“For far too many families, diabetes has become a common and painful reality,” said Dr. Harold Goldstein, executive director of the California Center for Public Health Advocacy. “In very stark terms, this study shows local health care providers and policymakers the enormity of the diabetes epidemic in their counties.”

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Study aims to boost health of immigrant Latino farmworkers


UC Davis, UC Berkeley participate in $3M study.

A new, collaborative study aimed at designing and evaluating worksite-based health programs to lower the risk of obesity and diabetes among immigrant Latino farmworkers has been launched under the leadership of UC Davis.

The new five-year study, to be carried out through a partnership between UC Davis; Reiter Affiliated Companies, a large California berry grower; and the Health Initiative of the Americas at UC Berkeley; was recently funded with more than $3 million in grant funds from the National Institute of Diabetes, Digestive and Kidney Diseases.

“Latino farmworkers harvest much of our fruit and vegetables, yet they face obesity and diabetes rates much higher than the general population,” said lead investigator Marc Schenker, director of the UC Migration and Health Research Center and the Western Center for Agricultural Health and Safety, and a distinguished professor in UC Davis’ Department of Public Health Sciences.

He noted that the prevalence of obesity and diabetes has rapidly increased during the past decade in the United States. Among Latinos, the prevalence of overweight and obesity is now an alarming 78 percent, markedly higher than in the general population. Furthermore, the prevalence of diabetes among Latinos in the U.S. is almost twice that of non-Latino whites.

“To address that problem, we have created and are evaluating an obesity and diabetes prevention program that can be delivered to workers in the field,” Schenker said.

The study will include food and nutrition educational programs at the participants’ on-farm worksites, as well as exercise activities such as Zumba classes. All programs are led by community health workers or “promotoras.”

The study focuses on ranches in Salinas and Watsonville, but the ultimate goal is to disseminate the intervention program to farms throughout the state and country.

The program is designed to improve health outcomes among the farmworkers participating in the study and to evaluate those outcomes, as well as the economic impact for the employer.

“We hope that the economic benefits — which we anticipate will be demonstrated and quantified through this study — will help convince other companies in the agricultural industry to adopt similar programs,” Schenker said.

He added that Reiter Affiliated Cos. is a model industry partner for this study because it is already invested in the health of its workers.

Co-investigators on the study include Daniel Sumner, a professor of agricultural and resource economics at UC Davis and director of the UC Agricultural Issues Center; Nancy Keim, an adjunct professor in the UC Davis Department of Nutrition; Heejung Bang, a professor of biostatistics at UC Davis; and Xochitl Castaneda, director of the Health Initiative of the Americas at UC Berkeley.

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