UC San Diego-based study looks at differentiation of hESCs in endocrine cell progression.

Maike Sander, UC San Diego

Type 1 and type 2 diabetes results when beta cells in the pancreas fail to produce enough insulin, the hormone that regulates blood sugar. One approach to treating diabetes is to stimulate regeneration of new beta cells.

There are currently two ways of generating endocrine cells (cell types, such as beta cells, that secrete hormones) from human embryonic stem cells, or hESCs: either generating the cells in vitro in culture or transplanting immature endocrine cell precursors into mice.

Researchers from the UC San Diego School of Medicine, collaborating with scientists from San Diego-based biotech company ViaCyte Inc., looked at the differences and similarities between these two types of hESC-derived endocrine cell populations and primary human endocrine cells, with the longer-term goal of developing new stem cell therapies for diabetes.

The results of their study will be published online today (Jan. 10), in advance of the Feb. 7 print edition of the journal Cell Stem Cell.

The scientists compared gene expression and chromatin architecture – the structure of combined DNA and proteins that make up the nucleus of the cell, in which dynamic remodeling occurs at various stages of differentiation – in both primary human endocrine cells and hESC-derived cells.

“We found that the endocrine cells retrieved from transplanted mice are remarkably similar to primary human endocrine cells,” said principal investigator Maike Sander, M.D., professor of pediatrics and cellular and molecular medicine, and director of UC San Diego’s Pediatric Diabetes Research Center. “This shows that hESCs can differentiate into endocrine cells that are almost indistinguishable from their primary human counterparts.”

However, the researchers observed that endocrine cells produced in vitro lack features of primary endocrine cells and fail to express the majority of genes that are critical for endocrine cell function. Consistent with this finding, these cells are not able to reverse diabetes in diabetic animal models.

Read more

Computer modeling eyes cell metabolism as trigger for the increasingly prevalent disease.

Jamey Marth, UC Santa Barbara

While legions of medical researchers have been looking to understand the genetic basis of disease and how mutations may affect human health, a group of biomedical researchers at UC Santa Barbara is studying the metabolism of cells and their surrounding tissue, to ferret out ways in which certain diseases begin. This approach, which includes computer modeling, can be applied to type 2 diabetes, autoimmune diseases and neurodegenerative diseases, among others.

Scientists at UC Santa Barbara have published groundbreaking results of a study of type 2 diabetes that point to changes in cellular metabolism as the triggering factor for the disease, rather than genetic predisposition. Type 2 diabetes is a chronic condition in which blood sugar or glucose levels are high. It affects a large and growing segment of the human population, especially among the obese. The team of scientists expects the discovery to become a basis for efforts to prevent and cure this disease.

The current work is based on a previous major finding by UC Santa Barbara’s Jamey Marth, who determined the identity of the molecular building blocks needed in constructing the four types of macromolecules of all cells when he was based at the Howard Hughes Medical Institute in La Jolla in 2008. These include the innate, genetic macromolecules, such as nucleic acids (DNA and RNA) and their encoded proteins, and the acquired metabolic macromolecules known as glycans and lipids. Marth is a professor in the Department of Molecular, Cellular, and Developmental Biology and the Biomolecular Science and Engineering Program; and holds the John Carbon Chair in Biochemistry and Molecular Biology and the Duncan and Suzanne Mellichamp Chair in Systems Biology. He is also a professor with the Sanford-Burnham Medical Research Institute in La Jolla.

“By studying the four types of components that make up the cell, we can, for the first time, begin to understand what causes many of the common grievous diseases that exist in the absence of definable genetic variation, but, instead, are due to environmental and metabolic alterations of our cells,” said Marth. UC Santa Barbara is the only institution studying these four types of molecules in the cells while also using computational modeling to determine their functions in health and disease, according to Marth.

The new study, published in the Dec. 27 issue of PLOS ONE, relies on computational systems biology modeling to understand the pathogenesis of type 2 diabetes.

“Even in the post-genomic era, after the human genome has been sequenced, we’re beginning to realize that diseases aren’t always in our genes — that the environment is playing a major role in many of the common diseases,” said Marth.

Read more

Patients who give their doctors high marks in communication more likely to fill prescriptions.

Neda Ratonawongsa, UC San Francisco

Even the best medicines in the world can be rendered ineffective if they are not taken as prescribed.  The problem known as medication “non-adherence” is a major health issue in the United States, contributing to worse outcomes for people who have diabetes and other chronic diseases.

Now a study led by researchers at the University of California, San Francisco (UCSF), San Francisco General Hospital and Trauma Center (SFGH) and the Kaiser Permanente Division of Research has identified a significant factor that contributes to poor drug adherence – ineffective communication.

Described in the journal JAMA Internal Medicine, formerly known as the Archives of Internal Medicine, the study looked at 9,377 patients taking medications to lower their blood sugar, blood pressure or cholesterol.

These patients were asked through questionnaires to rate how well their doctors communicated with them. Patient medication adherence was determined by measuring delays in refilling prescriptions. The patients who gave their doctors poor marks in communicating were less likely to adhere to their medications.

The work suggests preparing doctors to be better communicators may help improve medication adherence and ultimately health outcomes, said lead author Neda Ratanawongsa, M.D., M.P.H., an assistant professor in the UCSF Department of Medicine and the UCSF Center for Vulnerable Populations at SFGH.

“Communication matters,” Ratanawongsa said. “Thirty percent of people [in the study] were not necessarily taking their medications the way their doctors thought they were. Rates for non-adherence were 4 to 6 percent lower for patients who felt their doctors listened to them, involved them in decisions and gained their trust. By supporting doctors in developing meaningful relationships with their patients, we could help patients take better care of themselves.”

The work is part of the Diabetes Study of Northern California (DISTANCE), which is designed to evaluate quality of care and to identify reasons for disparities where they exist.

“What is unique about our study is that we found that medication adherence is better if the physician has established a trusting relationship with the patient and prioritizes the quality of communication, even if that communication is not specifically focused on medication adherence,” added Andrew Karter, Ph.D., a senior research scientist with the Kaiser Permanente Division of Research and the principal investigator of DISTANCE.

Read more

Study suggests preventive role for vitamin D3 in this disease.

Cedric Garland, UC San Diego

A study led by researchers from the UC San Diego School of Medicine has found a correlation between vitamin D3 serum levels and subsequent incidence of type 1 diabetes. The six-year study of blood levels of nearly 2,000 individuals suggests a preventive role for vitamin D3 in this disease. The research appears the December issue of Diabetologia, a publication of the European Association for the Study of Diabetes (EASD).

“Previous studies proposed the existence of an association between vitamin D deficiency and risk of and type 1 diabetes, but this is the first time that the theory has been tested in a way that provides the dose-response relationship,” said Cedric Garland, Dr.P.H., FACE, professor in UCSD’s Department of Family and Preventive Medicine.

This study used samples from millions of blood serum specimens frozen by the Department of Defense Serum Registry for disease surveillance. The researchers thawed and analyzed 1000 samples of serum from healthy people who later developed type 1 diabetes and 1,000 healthy controls whose blood was drawn on or near the same date but who did not develop type 1 diabetes. By comparing the serum concentrations of the predominant circulating form of vitamin D – 25-hydroxyvitamin D (25(OH)D) – investigators were able to determine the optimal serum level needed to lower an individual’s risk of developing type 1 diabetes.

Based mainly on results of this study, Garland estimates that the level of 25(OH)D needed to prevent half the cases of type 1 diabetes is 50 ng/ml. A consensus of all available data indicates no known risk associated with this dosage.

“While there are a few conditions that influence vitamin D metabolism, for most people, 4,000 IU per day of vitamin D3 will be needed to achieve the effective levels,” Garland suggested. He urges interested patients to ask their health care provider to measure their serum 25(OH)D before increasing vitamin D3 intake.

Read more

Medical school leads funding with $205M.

UC Davis professor Oliver Fiehn, director of the West Coast Metabolomics Center, received $9.3 million as a startup grant from the National Institutes of Health.

Research funding at the University of California, Davis, totaled nearly $750 million during the fiscal year that ended June 30, a record high for the university and an increase of about $65 million from the previous year’s total.

“This record funding for our campus underscores the strength and breadth of research at UC Davis,” said Chancellor Linda P.B. Katehi. “But university research is about more than just new ideas. It translates into jobs, economic health and the long-term competitiveness of our state and nation.”

The new total places the campus fourth in the University of California system in external research funding, up from fifth the year before. UC Davis has had the fastest growth of any of the 10 UC campuses in research funding since 1995.

“These figures are incredibly uplifting,” said Harris Lewin, vice chancellor for research at UC Davis. “The UC Davis faculty, rightly, have much to be proud of, and the Office of Research is privileged to be part of that success story.”

Examples of grants awarded to UC Davis faculty in the past year include:

• A $25 million, five-year program to improve food security in the developing world, funded by the U.S. Agency for International Development
• $34 million from the National Institutes of Health to a consortium including UC Davis for development of new mouse models of diseases such as cancer, obesity and diabetes, a key step toward finding better ways to prevent and treat these diseases
• $12 million from a joint program of the National Science Foundation and the Japan Science and Technology Agency to further research into generating biofuels from algae
• $5.6 million from the John Templeton Foundation to study the psychology of gratitude
• $4.8 million from the U.S. Department of Agriculture to fight child obesity in the Central Valley, and $4 million from the U.S. Department of Health and Human Services to establish a Center for Poverty Research
• $580,000 from the Andrew W. Mellon Foundation to study engagement of students and other audiences with classical music

The record total brings UC Davis three-quarters of the way towards a goal Katehi set in fall 2011 to reach a billion dollars in research funding by 2020. Katehi’s “2020 Initiative” also calls for increased undergraduate enrollment and new faculty hires. The new professors would generate additional research grants and programs that address the world’s most critical issues in food, water, health, society, energy and the environment, as well as providing new opportunities for students to learn.

Much of the funding for basic research at UC Davis supports jobs for professional scientists, technical staff, postdoctoral researchers and graduate students. Research projects may also lead to commercially applicable technologies and startup companies. The UC Davis Office of Research filed 224 new invention disclosures with the U.S. Patents and Trademarks Office in 2011-12, bringing UC Davis’ total portfolio of inventions to 1,190. Since fiscal year 2003-4, 44 startup companies have been formed at UC Davis.

Read more

Program named after legendary UCSF nurse Peggy Huang.

Members of the UCSF Madison Clinic for Pediatric Diabetes Saleh Adi and Colette O’Brien work with nursing student Dara Nunn to check on a patient with diabetes.

An epidemic is sweeping the nation and world: diabetes. Almost 26 million children and adults in the United States — and 346 million worldwide — have the disease. Another 79 million Americans are considered to have pre-diabetes.

Now, thanks to a generous $1.5 million gift from a member of the Diabetes Center Leadership Council who has a child with diabetes, UC San Francisco will be among the first in the country to educate and train nurses specifically to care for diabetes patients across their lifespan by establishing a new academic minor in diabetes at the UCSF School of Nursing.

“With increasing rates of obesity and an aging population, we need to train more nurses who can help patients manage the disease in a very knowledgeable way,” says UCSF’s Kit Chesla, R.N., Ph.D., FAAN, a professor, diabetes researcher, and Shobe Endowed Chair in Ethics and Spirituality.

The Madison Clinic Peggy Huang Diabetes Nurse Fellows Program will prepare advanced practice nursing students to sit for qualification exams to become nationally board certified in advanced diabetes management (BC-ADM). As such, they will help patients manage their diabetes from both medical and behavioral perspectives. For example, the nurses might adjust patients’ medication regimens, and help those who are struggling with their diets to set realistic goals and develop concrete plans for adopting healthier lifestyles.

The minor’s inaugural class of three to six students will enroll in the spring of 2013. The classes are also open to any other UCSF nursing student with an interest in the field. These pioneering students will begin by taking three courses: one each on advanced clinical management of type 1 and type 2 diabetes in children and adults, and one on the behavioral aspects of diabetes management. They will then complete clinical rotations in the UCSF Madison Clinic for Pediatric Diabetes, the UCSF Justine K. Schreyer Adult Diabetes Care Center, or other family practice and community clinics that treat a significant number of patients with diabetes.

Both the curriculum and clinical training are interprofessional ventures between the schools of medicine and nursing. While the program is directed by the School of Nursing, pediatric diabetes physicians Saleh Adi, M.D., and Steve Gitelman, M.D. — both of whom are leaders in the Madison Clinic for Pediatric Diabetes — will teach some elements of the curriculum and help train nurses in the clinic.

“This is just the latest example of the collaborative spirit among the basic research, clinical research, and patient care programs that make up diabetes at UCSF,” says Matthias Hebrok, director of the UCSF Diabetes Center.

Read more

More intensive screening of patients recommended.

April Armstrong, UC Davis

An analysis of 27 studies linking psoriasis in 314,000 individuals with diabetes has found strong correlation between the scaly skin rash and the blood sugar disorder that predisposes patients to heart disease, say UC Davis researchers who led the review.

The findings appear in an article titled “Psoriasis and the risk of diabetes: a systematic review and meta-analysis,” which is now online in the Archives of Dermatology.

“Our investigation found a clear association between psoriasis and diabetes,” said April Armstrong, assistant professor of dermatology at UC Davis and principal investigator of the study. “Patients with psoriasis and their physicians need to be aware of the increased risk of developing diabetes so that patients can be screened regularly and benefit from early treatment.”

Psoriasis is a common skin problem that tends to run in families. It causes a raised red, flaky and sometimes itchy rash, often on the elbows and knees, although it can appear anywhere. It is believed to be an autoimmune disease, in which the body regards its own skin as foreign and mounts an inflammatory response.

Armstrong and her colleagues combined data from 27 observational studies of patients with psoriasis, in what is known as a meta-analysis. Five of the studies assessed the incidence of diabetes– that is, how many patients with psoriasis developed diabetes during the course of a study, which ranged from 10 to 22 years. The other studies assessed the prevalence of diabetes — how many patients already had diabetes at the outset of a study. Altogether, the studies evaluated more than 314,000 people with psoriasis and compared them to 3.7 million individuals (controls) without the disease.

Read more

The highest prevalence is among Pacific Islanders, South Asians and Filipinos.

Alka Kanaya, UC San Francisco

Rates of diagnosed diabetes are much higher among some Asian subgroups than is apparent when aggregating all Asians as a whole, according to a new study by the Kaiser Permanente Division of Research and the University of California, San Francisco, which appears in the current online issue of Diabetes Care.

In this first study to look at Asian subgroup differences in a population with uniform access to health care, there was considerable variation among the seven largest Asian and Pacific Islander subgroups. Pacific Islanders, South Asians and Filipinos had the highest diabetes prevalence (18.3 percent, 15.9 percent, and 16.1 percent respectively) and incidence (19.9, 17.2, 14.7 cases per 1000-person years, respectively) among all racial/ethnic groups, including minorities traditionally considered high risk, such as African Americans, Latinos and Native Americans.

“Our findings are consistent with national surveillance which reports that Asians generally have a higher prevalence of diabetes relative to non-Hispanic whites, but lower than that of African Americans and Latinos,” explained Andrew Karter, a senior research scientist with the Kaiser Permanente Division of Research and the lead author of the study.

“However, when looking at the Asian subgroups separately, we find that Pacific Islanders, South Asians and Filipinos stand out as having greater risk. Studying diabetes in Asians ‘as a whole’ obscured these subgroup differences because the high diabetes risk among Pacific Islanders, South Asians and Filipinos was counterbalanced by much lower rates among the large population of Chinese and several smaller Asian subgroups. ”

The number of Americans of Asian and Pacific Islander ethnicity increased by 43 percent between the 2000 and 2010 censuses, and they now comprise 5 percent of the U.S. population. National health statistics typically have lumped all Asians into a single group when evaluating racial differences in health outcomes, precluding evaluation of subgroup differences. Most national health surveys before 2000 classified Asians as ‘other race’ or, if recognized, combined them with Pacific Islanders.

“That would be like combining blacks, Latinos and whites together into one ethnic group” said Alka Kanaya, M.D., an associate professor of medicine at UCSF and a co-author on the study. “As a result, the variation among Asian and Pacific Islanders subgroups has been neglected. In fact, the aggregated statistics may be completely misleading given the variation in the representation of each subgroup across the U.S.”

Read more

UC Davis-led consortium will help scientists better understand diseases like diabetes, cancer.

Oliver Fiehn, UC Davis

With a $9.3 million startup grant from the National Institutes of Health, the University of California, Davis, has announced plans to open the West Coast Metabolomics Center, a high-tech consortium of research and service laboratories that will help scientists better understand and develop more effective treatments for complex diseases like diabetes, cancer and atherosclerosis.

The facility, which will be housed within the UC Davis Genome Center, will celebrate its grand opening Oct. 8 with a mini-symposium featuring UC Davis and regional scientists, and corporate supporters.

Metabolomics is a new field that looks at the biochemical changes taking place in living cells during metabolism. The West Coast Metabolomics Center at UC Davis will use more than 30 mass spectrometers — instruments for analyzing chemical structures — to target thousands of different molecules produced in cells, allowing researchers to look at changes taking place at specific times and under specific environmental conditions.

“The NIH recognizes metabolism as a very important part of human physiology and disease processes,” said Oliver Fiehn, professor of molecular and cellular biology and director of the new center. “When you analyze metabolism, you can tell the state of the body at the onset and during the progression of diseases ranging from cardiovascular disease to cancer.”

The new center brings together existing UC Davis service facilities in mass spectrometry, nuclear magnetic resonance and imaging, with research labs across the campus, Fiehn said.

It will help researchers throughout the western U.S. with small grants for annual pilot and feasibility studies, provide courses, statistics and bioinformatics services, and perform metabolomic analyses on a fee-for-service basis. The center is designed to be self-sustaining within five years.

One of researchers who plans to use the new center is UC Davis professor Bruce German, who studies lipid metabolism, especially in milk production, in the Department of Food Science and Technology.

“This new center shows the effects of the university’s long-term investments into biochemistry and genomics,” German said.

Juvenile diabetes

One of the center’s first big projects will be as part of a large international study, led by the NIH, to look for environmental causes of childhood diabetes. Juvenile, or type 1, diabetes is an autoimmune disease that causes the body to destroy pancreatic cells that produce insulin, and people with the disease must inject insulin regularly in order to survive.

Called the TEDDY study — The Environmental Determinants of Type 1 Diabetes in the Young — the project will track nearly 8,000 children over a three-year period to try to identify factors such as infections, diet, stress or other conditions that may trigger the disease.

“We know that children who get type 1 diabetes all have certain gene signatures, but most children with those same genes don’t get the disease,” Fiehn said. “Researchers now believe there’s an environmental trigger — something that activates those genes and causes the disease. Metabolomics is a way to try to identify those environmental triggers by seeing what’s happening inside the cells over time. In addition, metabolomics is a chemical screening tool that might find further environmental cues, including pollutants.”

The West Coast Metabolomics Center will analyze blood samples taken from children every three months during the study period, providing data to researchers that may help them identify a single factor or series of factors that trigger the disease. The TEDDY consortium will pay more than $1.5 million for the services provided by the new center.

Individualized medicine

Another promising aspect of metabolomics research is creating individualized treatments for people with certain diseases, or choosing the best available treatment for a patient.

Metabolomics could be used to determine the best dose of treatment for a patient. People with higher metabolisms may need higher doses of drugs than people with lower metabolisms, for example.

“Understanding metabolomics and disease response will help scientists to develop new therapeutic strategies,” said professor Ralph de Vere White, director of the UC Davis Comprehensive Cancer Center. “This metabolomics research center will allow the UC Davis Comprehensive Cancer Center to advance this exciting area in cancer research, more deeply understand underlying mechanisms, and improve treatment options for patients.”

The West Coast Metabolomics Center at UC Davis has received instrumentation support from mass spectrometry equipment companies Agilent Inc. and LECO Corp.

About UC Davis

For more than 100 years, UC Davis has engaged in teaching, research and public service that matter to California and transform the world. Located close to the state capital, UC Davis has more than 32,000 students, more than 2,500 faculty and more than 21,000 staff, an annual research budget that exceeds $684 million, a comprehensive health system and 13 specialized research centers. The university offers interdisciplinary graduate study and more than 100 undergraduate majors in four colleges — Agricultural and Environmental Sciences, Biological Sciences, Engineering, and Letters and Science. It also houses six professional schools — Education, Law, Management, Medicine, Veterinary Medicine and the Betty Irene Moore School of Nursing.

Study investigates relative effects of fructose, glucose.

Lars Berglund, UC Davis

Prolonged fructose consumption may contribute to the development of metabolic syndrome, a combination of medical disorders that, when occurring together, increases the risk of developing cardiovascular disease and diabetes.

The findings, just published online in the journal Nutrition & Metabolism, are derived from a UC Davis study that investigated the relative effects of fructose or glucose consumption on 32 older, overweight or obese men and women who consumed glucose- or fructose-sweetened beverages, which provided 25 percent of their energy requirements for 10 weeks.

Consumption of fructose, but not glucose, impacted various parameters associated with metabolic syndrome, including increased circulating concentrations of uric acid, which is known to be higher in people with metabolic syndrome, increased GGT activity, which is an indicator of liver dysfunction, and production of a type of protein known as RBP-4, associated with increased insulin resistance. No previous studies have investigated the effects of glucose or fructose consumption on circulating levels of RBP-4.

The study design involved three phases, including a two-week inpatient baseline period, an eight-week outpatient intervention period, and a two-week inpatient intervention period.

During baseline, subjects resided in the UC Davis Clinical and Translational Science Center’s Clinical Research Center (CCRC) for two weeks before beginning the outpatient intervention, consuming either fructose- or glucose-sweetened beverages. They returned to the CCRC for the final two weeks of intervention.

Fasting and 24-hour blood collections were performed at baseline and following 10 weeks of intervention for measurement of plasma concentrations of uric acid, RBP-4 and liver enzyme activities.

The study’s first results, published in 2009, showed that visceral adipose volume (fat inside the abdominal cavity) was significantly increased only in subjects consuming fructose, along with increases in several circulating lipids and a decrease in insulin sensitivity, although both groups exhibited similar weight gain.

Senior author Peter Havel, a UC Davis professor with joint appointments in the Department of Molecular Biosciences in the School of Veterinary Medicine and the Department of Nutrition, is currently the principal investigator for a follow-up study comparing impacts of glucose, fructose and high-fructose corn syrup in younger patients. His colleague and collaborator, Kimber Stanhope, directed and coordinated the clinical research study.

Glucose and fructose are both simple sugars, and equal parts of each is the recipe for table sugar (sucrose). The pure glucose and fructose that were used to sweeten the beverages in this study are not found in nature. Most fruits and honey contain comparable amounts of glucose, fructose and sucrose. Grains such as wheat, oats, corn and barley contain large amounts of glucose (and negligible amounts of fructose), but the glucose is packaged as long chains that are called starch or complex carbohydrate.

Co-author Lars Berglund, director of the UC Davis Clinical and Translational Science Center, points out that fruit juices typically feature more concentrated forms of these sugars, while fruits and vegetable contain fiber and other beneficial components.

“It’s healthier to eat apples than to drink apple juice,” said Berglund.

Other authors include former graduate students Chad Cox, James Graham, Bonnie Hatcher, Steven Griffen and John McGahan, all of UC Davis; Jean Marc Schwarz of Touro University, Vallejo, Calif.; Andrew Bremer of Vanderbilt University, Nashville; and Nancy Keim of UC Davis and the U.S. Department of Agriculture, Davis.

This research was supported with funding from National Institutes of Health (RO1 HL-075675), the NIH’s National Center for Research Resources (UL1 RR024146), and the NIH Roadmap for Medical Research. Havel’s laboratory receives support from the NIH (HL-091333, DK-097307, and DK-095980) and a Multicampus Award (#142691) from the University of California, Office of the President, and Keim’s research is supported by intramural U.S. Department of Agriculture-Agricultural Research Service (ARS) Current Research Information System (CRIS) grant 5306-51530-016-00D.

UCSF study suggests stress-amplifying TXNIP protein may be powerful new drug target.

Feroz Papa, UC San Francisco

At its most fundamental level, diabetes is a disease characterized by stress — microscopic stress that causes inflammation and the loss of insulin production in the pancreas, and system-wide stress due to the loss of that blood-sugar-regulating hormone.

Now, researchers led by scientists at the University of California, San Francisco, have uncovered a new key player in amplifying this stress in the earliest stages of diabetes: a molecule called thioredoxin-interacting protein (TXNIP). The molecule, they’ve discovered, is central to the inflammatory process that leads to the death of the cells in the human pancreas that produce insulin.

“This molecule does something remarkable — it takes stress and makes it worse,” said the senior author of the study, UCSF’s Feroz Papa, M.D., Ph.D., an associate professor of medicine at UCSF and a member of the UCSF Diabetes Center and the California Institute for Quantitative Biosciences (QB3).

The study is published this week in the journal Cell Metabolism, with a parallel study by researchers at Washington University in St. Louis. Both studies were funded by the Juvenile Diabetes Research Foundation (JDRF).

The work provides a roadmap for finding new drugs that could target and shut down the action of TXNIP, thus preventing or stalling the inflammatory processes it amplifies. Researchers in the field believe that this strategy could benefit people in the early days of the disease, when diabetes is first developing or is soon to develop — a time referred to as the “honeymoon” period.

Read more

Study authors recommend adding palliative care to diabetes management.

Rebecca Sudore

Almost half of adults with type 2 diabetes report acute and chronic pain, and close to one quarter report neuropathy, fatigue, depression, sleep disturbance and physical or emotional disability, according to a study of more than 13,000 adults conducted by researchers at the San Francisco VA Medical Center, the University of California, San Francisco, and the Kaiser Permanente Division of Research in Oakland. The researchers also found significant rates of shortness of breath, nausea and constipation.

Patients in the study reported significant pain and non-pain symptoms across the entire course of the disease, among all age groups, with prevalence increasing as people neared the end of their lives.

The findings appear in the Journal of General Internal Medicine and are available online on Aug. 3 at www.SpringerLink.com. According to the authors, it is the largest observational study to assess a full range of pain and non-pain symptoms among patients with type 2 diabetes, and the first to characterize the kinds of symptoms that patients experience.

“Adults living with type 2 diabetes are suffering from incredibly high rates of pain and non-pain symptoms, at levels similar to patients with living with cancer,” said lead author Rebecca Sudore, a staff physician at SFVAMC and associate professor of medicine at UCSF.

She noted that tens of millions of Americans have type 2 diabetes.

“The field of diabetes has focused, and rightfully so, on decreasing patients’ blood sugar, blood pressure and cholesterol levels in attempt to prevent complications such as cardiovascular disease, kidney failure, amputations and blindness,” said Andrew J. Karter, Ph.D., a principal investigator of the DISTANCE and Diabetes & Aging Studies, and senior research scientist at Kaiser. “However, our observations provide an important wake-up call for clinicians to not wait until the latest stages of diabetes to focus on these patient-reported outcomes, but rather to consider early palliative care as part of usual chronic disease management.”

Palliative care is specialized medical care for people with serious illness that provides an added layer of support in addition to regular disease management, with the goal of relieving symptoms and improving quality of life, explained Sudore. She noted that other studies suggest that seriously ill patients who receive palliative care live longer with a better quality of life.

“Palliative care has already begun to be woven into the care provided to patients with cancer, heart failure and kidney failure,” she said. “Our results highlight the need to expand diabetes management to also include the palliative care model.”

The research team surveyed 13,171 adults with diabetes, aged 30 to 75 years, who were enrolled in Kaiser Permanente Northern California and participated in the NIH-funded Diabetes Study of Northern California (DISTANCE) and its ancillary Diabetes & Aging Study.

Adults over the age of 60 reported more physical symptoms such as pain, whereas adults younger than 60 reported more psychosocial symptoms such as fatigue and depression. Symptom burden remained high even after the researchers accounted for other medical illnesses and duration of diabetes. Results were based on self-reported symptoms and chart review.

In type 2 diabetes, the most common form of the disease, patients’ blood sugars become chronically elevated, which in turn damages blood vessels and nerves leading to and from the heart, brain, kidneys, gastrointestinal tract, eyes, ears, legs and feet. This damage can lead to serious illness and death.

Dean Schillinger, M.D., of the UCSF Center for Vulnerable Populations and UCSF Division of General Internal Medicine at San Francisco General Hospital, is senior co-author of the study. He also is director of the California Diabetes Program, a federally-funded program that is administered by UCSF for the California Department of Public Health.  Elbert S. Huang, M.D., of the University of Chicago, is the co-principal investigator for the Diabetes & Aging Study and co-director for the Chicago Center for Diabetes Translation Research.

Co-authors include Andrew J. Karter, Ph.D., Howard H. Moffet, M.P.H., Jennifer Liu, M.P.H., Alyce Adams, Ph.D., and Rachael Whitmer, Ph.D., from the Division of Research, Kaiser Permanente Northern California; Elbert S. Huang, M.D., M.P.H., Neda Laiteerapong, M.D., and Priya John, M.P.H., from the University of Chicago; Yael Schenker, M.D., from the University of Pittsburgh; and Yinghui Miao, M.P.H. from UCSF.

Funds were provided by the National Institute of Diabetes, Digestive and Kidney Diseases, the National Institute of Child Health and Human Development and the National Center for Research Resources. Sudore is supported by funds from the Department of Veterans Affairs. Schillinger is supported by a grant from Agency for Healthcare Research and Quality and a NIH Clinical and Translational Science Award.

About the San Francisco VA Medical Center

SFVAMC has the largest medical research program in the national VA system, with more than 200 research scientists, all of whom are faculty members at UCSF.

About UCSF

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. For further information, please visit www.ucsf.edu.

About the Kaiser Permanente Division of Research

The Kaiser Permanente Division of Research conducts, publishes and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and the society at large. It seeks to understand the determinants of illness and well-being and to improve the quality and cost-effectiveness of health care. Currently, DOR’s 500-plus staff is working on more than 250 epidemiological and health services research projects.