TAG: "Diabetes"

Type 1 diabetes drug proves effective in clinical trial


Drug developed by UCSF researcher shows promise in blocking advance of disease.

Child with diabetesAn experimental drug designed to block the advance of type 1 diabetes in its earliest stages has proven strikingly effective over two years in about half of the patients who participated in the phase 2 clinical trial.

Patients who benefited most were those who still had relatively good control of their blood sugar levels and only a moderate need for insulin injections when the trial began. With the experimental drug, teplizumab, they were able to maintain their level of insulin production for the full two years – longer than with most other drugs tested against the disease.

Results are published online in the journal Diabetes, and will appear in the November issue of the print edition.

The treatment did not benefit all patients. Some lost half or more of their ability to produce insulin – a drop similar to many of the controls not receiving the drug. Reasons for the different responses are unclear, but likely involve differences in the metabolic condition of the patients and in the severity of their disease at the trial’s start, the researchers said.

Jeffrey Bluestone, UC San Francisco

Jeffrey Bluestone, UC San Francisco

“The benefits of treatment among the patients who still had moderately healthy insulin production suggests that the sooner we can detect the pre-diabetes condition and get this kind of drug onboard, the more people we can protect from the progressive damage caused by an autoimmune attack,” said Jeffrey Bluestone, Ph.D., co-leader of the research and A.W. and Mary Clausen Distinguished Professor at UC San Francisco, who collaborated in developing the drug.

The clinical trial was led by Kevan Herold, M.D., Ph.D., a professor of immunobiology and deputy director for translational science at Yale University. He and Bluestone have collaborated on four previous clinical trials of the experimental drug.

“We are very excited by the efficacy of the drug,” Herold said. “Some of our patients and families have described a real impact on their diabetes.”

Bluestone, an immunologist who is now executive vice chancellor and provost at UCSF, developed teplizumab in collaboration with Ortho Pharmaceuticals in 1987. He is a leader in research that aims to understand how and why the immune system attacks the body’s own tissues and organs, and to develop drug strategies to eliminate the autoimmune response without producing severe side effects.

Read more

CATEGORY: NewsComments Off

A second amyloid may play a role in Alzheimer’s disease


UC Davis study is first to identify deposits of amylin in brains of people with Alzheimer’s.

Amylin molecule

A protein secreted with insulin travels through the bloodstream and accumulates in the brains of individuals with type 2 diabetes and dementia, in the same manner as the amyloid beta (Αβ) plaques that are associated with Alzheimer’s disease, a study by researchers with the UC Davis Alzheimer’s Disease Center has found.

The study is the first to identify deposits of the protein, called amylin, in the brains of people with Alzheimer’s disease, as well as combined deposits of amylin and Aβ plaques, suggesting that amylin is a second amyloid as well as a new biomarker for age-related dementia and Alzheimer’s.

“We’ve known for a long time that diabetes hurts the brain, and there has been a lot of speculation about why that occurs, but there has been no conclusive evidence until now,” said UC Davis Alzheimer’s Disease Center Director Charles DeCarli.

“This research is the first to provide clear evidence that amylin gets into the brain itself and that it forms plaques that are just like the amyloid beta that has been thought to be the cause of Alzheimer’s disease,” DeCarli said. “In fact, the amylin looks like the amyloid beta protein, and they both interact. That’s why we’re calling it the second amyloid of Alzheimer’s disease.”

“Amylin deposition in the brain: A second amyloid in Alzheimer’s disease?” is published online today (June 27) in the Annals of Neurology.

Read more

CATEGORY: NewsComments Off

UC Irvine researchers awarded $2.3M to create novel diabetes treatments


Grants will support islet cell transplantation and insulin sensor projects.

Elliot Botvinick, UC Irvine

Two UC Irvine research groups have received $2.27 million from the JDRF to develop innovative methods of treating and possibly curing Type 1 diabetes.

The JDRF, formerly the Juvenile Diabetes Research Foundation, awarded one grant to Jonathan Lakey, associate professor of surgery and biomedical engineering, and Elliot Botvinick, assistant professor of surgery and biomedical engineering; and another to Weian Zhao, assistant professor of pharmaceutical sciences and biomedical engineering. Lakey and Zhao are affiliated with the campus’s Sue & Bill Gross Stem Cell Research Center.

With $1.27 million in funding over three years, Lakey and Botvinick will try to find a way to successfully transplant encapsulated, stem cell-created pancreatic islets. In Type 1 diabetes, the pancreas cannot produce insulin – a hormone key to regulating carbohydrate and fat metabolism in the body – making daily insulin treatments necessary.

Jonathan Lakey, UC Irvine

The pancreas, an organ about the size of a hand, is located behind the lower part of the stomach. It makes insulin and enzymes that help the body digest and use food. Throughout the pancreas are clusters of cells called the islets of Langerhans. Islets are composed of several types of cells, including beta cells that make insulin.

In a previous study, Lakey helped show that transplanted encapsulated islets can create and secrete insulin. A major hurdle, though, is overcoming immune-system rejection of these transplanted islets.

The Lakey-Botvinick team – which includes researchers and products from UC Irvine, the University of Oxford, the Netherlands’ University of Groningen, Eastern Virginia Medical School, Islet Sheet Medical in San Francisco, Islet Sciences in New York and Danish pharmaceutical company Novo Nordisk – will explore the use of isolated islets in which the cells are encased in an ultrapure algae membrane.

The encapsulation chemistry allows for selective permeability, meaning that some small molecules, such as glucose and insulin, can pass across the barrier, while large antibodies and immunological molecules are blocked from entering into the space containing the islets.

Weian Zhao, UC Irvine

“Perhaps the greatest challenge in the field of islet transplantation is to make the metabolic benefits available to patients with Type 1 diabetes without the need for chronic immunosuppression,” said Lakey, who’s also director of UC Irvine Health’s Clinical Islet Program. “I believe that this technology has great promise for realizing our goal. And this welcome support from the JDRF should speed our progress.”

With the other grant, Zhao and his colleagues will try to develop an insulin sensor for the JDRF’s Artificial Pancreas Project, which supports the creation of an automated system to dispense insulin based on real-time changes in blood sugar levels. Central to such a device is a mechanism that can accurately determine blood insulin amounts to provide feedback control for the artificial pancreas.

Read more

CATEGORY: NewsComments Off

Alzheimer’s and low blood sugar in diabetes may trigger a vicious cycle


UCSF researcher urges caution on use of certain diabetes drugs in dementia patients.

Kristine Yaffe, UC San Francisco

A new UC San Francisco-led study looks at the close link between diabetes and dementia, which can create a vicious cycle.

Diabetes-associated episodes of low blood sugar may increase the risk of developing dementia, while having dementia or even milder forms of cognitive impairment may increase the risk of experiencing low blood sugar, according to the study published online today (June 10)  in JAMA Internal Medicine.

Researchers analyzed data from 783 diabetic participants and found that hospitalization for severe hypoglycemia among the diabetic, elderly participants in the study was associated with a doubled risk of developing dementia later. Similarly, study participants with dementia were twice as likely to experience a severe hypoglycemic event.

The study results suggest some patients risk entering a downward spiral in which hypoglycemia and cognitive impairment fuel one another, leading to worse health, said Kristine Yaffe, M.D., senior author and principal investigator for the study, and a UCSF professor of psychiatry, neurology and epidemiology based at the San Francisco VA Medical Center.

“Older patients with diabetes may be especially vulnerable to a vicious cycle in which poor diabetes management may lead to cognitive decline and then to even worse diabetes management,” she said.

Read more

CATEGORY: NewsComments Off

Californians with regular doctor more likely to get preventive care


Patients in “medical homes” more likely to get flu shots, receive regular care.

Too many cooks may spoil a recipe, and too many doctors may give you the flu.

That’s the takeaway from a new study by the UCLA Center for Health Policy Research that found that Californians who jump from provider to provider rather than seeing a regular doctor who coordinates their care may be less likely to get the kind of preventive treatment that protects against the flu and flare ups in their chronic conditions.

Specifically, the study used data from the 2009 California Health Interview Survey (CHIS) to estimate whether the approximately 4.76 million California adults with chronic conditions such as diabetes, asthma and heart disease had three key characteristics of “medical home” care. Those three characteristics are:

  • The patient saw a regular doctor over time rather than switching from provider to provider.
  • This regular doctor developed an individual treatment plan for the patient.
  • The doctor coordinated the patient’s care.

The result? Californians who had all three of these characteristics were the most likely to get a regular flu shot, compared with those without a usual source of care. They were also more likely to have seen their doctor five or more times in the past year and to have called their doctor with a question about their care. Additionally, they were the most confident about their ability to manage their health.

“Seeing the same doctor over time builds familiarity, trust and confidence for both provider and patient,” said Nadereh Pourat, the UCLA center’s director of research and lead author of the study. “And if that doctor takes a coordinated approach to their patients’ care, there seems to be a big payoff in terms of better health for their patients.”

Read more

CATEGORY: NewsComments Off

A new protein target for controlling diabetes


Fractalkine circulates in bloodstream and stimulates insulin secretion, researchers find.

Jerrold Olefsky, UC San Diego

Researchers at the UC San Diego School of Medicine have identified a previously unknown biological mechanism involved in the regulation of pancreatic islet beta cells, whose role is to produce and release insulin. The discovery suggests a new therapeutic target for treating dysfunctional beta cells and type 2 diabetes, a disease affecting more than 25 million Americans.

Writing in the April 11 issue of Cell, Jerrold M. Olefsky, M.D., associate dean for scientific affairs and distinguished professor of medicine, and colleagues say a transmembrane binding protein called fractalkine, which typically mediates cell-to-cell adhesion though its receptor, CX3CR1, can also be released from cells to circulate in the blood and stimulate insulin secretion.

“Our discovery of fractalkine’s role in beta cells is novel and has never been talked about in prior literature,” said Olefsky. More importantly, the research highlights fractalkine’s apparently vital role in normal, healthy beta cell function. In mouse models and in cultured human islets, the researchers found administering the protein stimulated insulin secretion and improved glucose tolerance, both key factors in diabetes.  In contrast, fractalkine had no effect in mice or islets when the fractalkine receptor was deleted.

“Whether or not decreased fractalkine or impaired fractalkine signaling are causes of decreased beta cell function in diabetes is unknown,” said Olefsky. “What we do know, without doubt, is that administration of fractalkine improves or restores insulin secretion in all of the mouse models we have examined, as well as in human islet cells.”

Olefsky said fractalkine or a protein analog could prove “a potential treatment to improve insulin secretion in type 2 diabetic patients. It might also improve beta cell function or beta cell health, beyond simply increasing insulin secretion, since fractalkine prevents beta cell apoptosis (cell death) and promotes the beta cell differentiation program.

“If successfully developed, this could be an important new complement to the therapeutic arsenal we use in type 2 diabetes,” Olefsky continued. “It is not likely to ‘cure’ diabetes, but it would certainly do a good job at providing glycemic control.”

Read more

CATEGORY: NewsComments Off

Research suggests popular diabetes drugs can cause abnormal pancreatic growth


The abnormalities may be associated with increased risk of neuroendocrine tumors.

Peter Butler, UCLA

Individuals who had taken a type of drug commonly used to treat Type 2 diabetes showed abnormalities in the pancreas, including cell proliferation, that may be associated with an increased risk of neuroendocrine tumors, according to a new study by researchers from UCLA and the University of Florida. Their findings were published online March 22 in the journal Diabetes.

The researchers, from the Larry L. Hillblom Islet Research Center at UCLA and the Diabetes Center at the University of Florida, found that cell mass was increased approximately 40 percent in the pancreases of deceased organ donors who had Type 2 diabetes and who had been treated with incretin therapy. This widely used type of treatment takes advantage of the action of a gut hormone known as glucagon-like peptide 1 (GLP-1) to lower blood sugar in the body.

Although there have been conflicting reports on the effects of the incretin class of drugs on the pancreas in animal studies, this is the first study to note such changes in the human pancreas. The research was made possible by a unique research consortium called nPOD (Network for Pancreatic Organ Donors with Diabetes), led by Dr. Mark Atkinson, a professor of pathology and pediatrics at the University of Florida. The network, which is funded by the Juvenile Diabetes Research Foundation, obtains pancreases from deceased organ donors, with permission of their next of kin, to better understand diabetes by investigating tissues of those with the disease.

“There is an increasing appreciation that animal studies do not always predict findings in humans,” said Dr. Peter Butler, director of UCLA’s Hillblom Islet Research Center and chief of the endocrinology, diabetes and hypertension unit. “The nPOD program is therefore a very precious resource.”

Read more

CATEGORY: NewsComments Off

Youth with diabetes at greater risk after transitioning to adult care


Study suggests need for additional support when leaving pediatric providers.

Debra Lotstein, UCLA

Debra Lotstein, UCLA

Type 1 diabetes is a condition in which the body does not produce insulin and cannot convert sugar, starches and other food into energy. Generally diagnosed during childhood or adolescence, the disease requires lifelong access to medical care and intensive daily self-management.

As children with Type 1 diabetes grow into young adults, they must leave their pediatric health care providers for adult providers. But the timing of this process and its impact on the young people’s health had not been fully explored.

In a new study published in the April issue of the journal Pediatrics and currently available online, UCLA researchers found that young people with Type 1 diabetes who had transitioned from pediatric to adult care were 2.5 times more likely to have chronically high blood glucose levels, putting them at higher risk for heart attacks, strokes, blindness and kidney failure later in life.

The estimated median age of patients when this transition occurred was 20.1 years, the researchers said, and 77 percent had left pediatric care by age 21.

The findings suggest that young adults need additional support and guidance when leaving their pediatric providers to avoid the risk of poor diabetes control.

Read more

CATEGORY: NewsComments Off

Nurses can play key role in reducing deaths from diseases


UCLA nursing professor co-authors World Health Organization report.

Linda Sarna, UCLA

Nurses and midwives can play a critical role in lessening people’s risk of cardiovascular diseases, cancers, chronic respiratory disease and diabetes, according to a groundbreaking new report issued by the World Health Organization and co-authored by a UCLA nursing professor.

These four non-communicable disease types account for a combined 60 percent of all deaths worldwide.

“The global burden of non-communicable diseases is already high and continues to grow in all regions of the world,” said Linda Sarna, a professor at the UCLA School of Nursing and co-author of the report. “Nurses and midwives have the expertise to help individuals and communities improve health outcomes.”

Sarna points out that since nurses and midwives make up more than 50 percent of all health care providers in most countries, they are the logical candidates to affect lifestyle changes among patients and increase health awareness. Worldwide, there are more than 19 million nurses and midwives, she said.

The 38-page report issued by the WHO highlights evidence-based, value-added nursing interventions that have been shown to reduce such risk factors as tobacco use, alcohol dependence, physical inactivity and unhealthy diets.

“The examples contained in the report are proven activities that nurses can start doing today to make a meaningful impact with their patients and in their community,” Sarna said. “Many of the interventions have been proven to reduce costs and improve the quality of care.”

Read more

CATEGORY: NewsComments Off

Funding from biotech company to advance diabetes research


Agreement with UC Merced professor an important show of faith.

Rudy Ortiz, UC Merced

Rudy Ortiz, UC Merced

UC Merced biology professor Rudy Ortiz is furthering his innovative research into diabetes with support from a major pharmaceutical company.

Ortiz’ work, developing new applications for medicines used to treat the effects of insulin resistance, has been funded by Amylin Pharmaceuticals LLC, a wholly owned subsidiary of Bristol-Myers Squibb Co., to the tune of $192,000 over two years.

Such funding agreements are common on other UC campuses and in comparable research institutions, and this agreement at UC Merced constitutes an important show of faith from the pharmaceutical industry in the young campus’s research capabilities.

“We will evaluate a drug that is traditionally used to address gluco-regulatory imbalance —the hallmark of diabetes — on a different aspect of diabetes,” Ortiz said. “This drug has also been proposed as a potential alternative to alleviate the hypertension associated with diabetes by improving the kidneys’ ability to regulate sodium.”

Read more

CATEGORY: NewsComments Off

Pediatric diabetes clinic marks 2nd anniversary in new Mission Bay home


UCSF clinic is steps away from the future UCSF Benioff Children’s Hospital.

Kendall Layous, and her mother Shonda, make drawings that are used as table-top covers, part of an art therapy program at the UCSF Madison Clinic for Pediatric Diabetes.

In the two years since the Madison Clinic for Pediatric Diabetes was established through an anonymous, $10 million gift, it has evolved into a state-of-the-art facility with innovative programs and a new home on the Mission Bay campus.

The Madison Clinic at Mission Bay, now located steps away from the future UCSF Benioff Children’s Hospital, offers comprehensive care for children and young adults with diabetes, with an emphasis on patient education, empowerment and the use of advanced technologies. It also has a commitment to advancing research in the management of diabetes in children.

A multidisciplinary team – including endocrinologists, clinical psychologists, nurses, diabetes educators, social workers, dietitians, and administrative staff – ensures patients’ varying needs are met.

“I don’t really manage diabetes. The parents do it all day, every day,” said Saleh Adi, M.D., medical director of the Madison Clinic and a pediatric endocrinologist. “Our job is to teach them how and provide them with the tools they need, and to be there for support and feedback whenever they need it.”

Shonda and Brad Layous know firsthand how much is required of parents with diabetic children. Their daughter Kendall was diagnosed with type 1 diabetes in April 2012, two days after her second birthday.

“Having a child with a serious health condition takes its toll on the entire family, so a bright spot in this emotional year for us was finding the Madison Clinic,” said Shonda Layous. “Our family knows that we are in the best care possible at the UCSF Madison Clinic, and its amazing staff and wonderful space give us comfort and confidence that we will partner with them for life to best manage her disease.”

There currently are 25.8 million children and adults in the United States, or 8.3 percent of the population, living with diabetes, according to the American Diabetes Association. One in every 400 children and adolescents younger than age 20 has the chronic disease, which is characterized by the body’s inability to regulate blood glucose, or blood sugar, levels.

With the incidence of both type 1 and type 2 diabetes in children on the rise, it is increasingly important to have skilled teams of diabetes health care providers who specialize in treating young people.

Read more

CATEGORY: NewsComments Off

International consortium builds ‘Google map’ of human metabolism


Recon 2 is most comprehensive virtual reconstruction of human metabolic network to date.

Researchers liken Recon 2 to Google mapping for its ability to merge complex details into a single, interactive map.

Building on earlier pioneering work by researchers at the University of California, San Diego, an international consortium of university researchers has produced the most comprehensive virtual reconstruction of human metabolism to date. Scientists could use the model, known as Recon 2, to identify causes of and new treatments for diseases like cancer, diabetes and even psychiatric and neurodegenerative disorders. Each person’s metabolism, which represents the conversion of food sources into energy and the assembly of molecules, is determined by genetics, environment and nutrition.

The researchers presented Recon 2 in a paper published online March 3 in the journal Nature Biotechnology.

Doctors have long recognized the importance of metabolic imbalances as an underlying cause of disease, but scientists have been ramping up their research on the connection as a result of compelling evidence enabled by the Human Genome Project and advances in systems biology, which leverages the power of high-powered computing to build vast interactive databases of biological information.

“Recon 2 allows biomedical researchers to study the human metabolic network with more precision than was ever previously possible. This is essential to understanding where and how specific metabolic pathways go off track to create disease,” said Bernhard Palsson, Galletti Professor of Bioengineering at UC San Diego Jacobs School of Engineering.

“It’s like having the coordinates of all the cars in town, but no street map. Without this tool, we don’t know why people are moving the way they are,” said Palsson.

He likened Recon 2 to Google mapping for its ability to merge complex details into a single, interactive map. For example, researchers looking at how metabolism sets the stage for cancerous tumor growth could zoom in on the “map” for finely detailed images of individual metabolic reactions or zoom out to look at patterns and relationships among pathways or different sectors of metabolism. This is not unlike how you can get a street view of a single house or zoom out to see how the house fits into the whole neighborhood, city, state, country and globe.  And just as Google maps brings together a broad set of data – such as images, addresses, streets and traffic flow – into an easily navigated tool, Recon 2 pulls together a vast compendium of data from published literature and existing models of metabolic processes.

Read more

CATEGORY: NewsComments Off