TAG: "Diabetes"

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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Community-based weight loss program aids diabetes management


Majority of participants in trial lost weight and reduced medication use.

Cheryl Rock, UC San Diego

Weight loss and control of blood sugar can reduce the risk of complications in patients with diabetes, but this is difficult for many to achieve. A UC San Diego School of Medicine randomized controlled trial of obese adults with type 2 diabetes suggests that participants enrolled in a community-based structured weight loss program are able to shed more pounds, improve blood sugar control and reduce or eliminate insulin use and other medications compared to a control group.

“Support and a tailored lifestyle intervention have been shown to reduce cardiovascular disease risk factors and adverse outcomes in people with diabetes,” said Cheryl L. Rock, Ph.D., R.D., professor of family and preventive medicine and principal investigator of the study. “However, most overweight individuals with type 2 diabetes do not receive this degree of support for changes in diet and physical activity to promote weight loss in their clinical care, due in part to constraints of time and training for most health care providers and clinicians.”

The results of the study, published in today’s (April 23) online issue of Diabetes Care, found that 72 percent of participants on the weight loss program that included portion-controlled foods and personalized counseling were able to change their insulin use compared with 8 percent of the control group. Similarly, other diabetes, cholesterol and blood pressure drugs were decreased or discontinued more often among the weight loss program enrollees.

According to the Centers for Disease Control and Prevention, 35 percent of adults in the United States are obese and 8 percent of adults are affected by diabetes.

“Weight loss is a primary strategy for successful management of type 2 diabetes due to its impact on glycemic control and improvements in cardiovascular disease risk factors,” said Rock. “These study results suggest that patients not only lose weight on structured commercial weight loss programs that include behavioral modification and individual support, but that this weight loss translates to significant improvements in diabetes control and cardio-metabolic parameters.”

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Saving diabetics from blindness in Libya


UC Berkeley grad student, professor, alum join forces in international public service project.

UC Berkeley optometry student Fatima Elkabti and professor Jorge Cuadros discuss a magnified digital image of a healthy retina.

A UC Berkeley graduate student in optometry, one of her professors and a Berkeley alumnus have joined forces to build a long-distance diagnostic project that has the potential to keep a large number of people in crisis-torn Libya from going blind.

The public service project involves training Libyan doctors to take detailed digital photographs inside patients’ eyes, of their retinas, as part of routine health care and put the images online for remote diagnosis of damage caused by diabetes before it’s too late. Too often, diabetes-related retinopathy isn’t caught until it causes symptoms, when treatment can no longer save vision.

The first 11 Libyan doctors underwent training for three days in February in Istanbul, in a seminar organized by the Avicenna Group and taught by Berkeley optometry professor Jorge Cuadros. Turkey was chosen as the training site for security reasons and because it is easily accessible from Libya.

If all goes according to plan, many more doctors will be trained over the next year, both in Libya and out — all because of a project that developed rapidly from a seed planted in a Diabetic Health Clinic class in Berkeley’s School of Optometry.

In the class, Cuadros taught students how to analyze photos of diabetic retinopathy as part of EyePACS, the California-based online initiative he co-founded to train people working in diabetes care to screen patients’ vision for remote diagnosis by certified eye doctors.

In his class was third-year optometry student Fatima Elkabti, who knows firsthand the toll that diabetes is taking in Libya, where the disease is rampant but greatly underdiagnosed. Elkabti’s father, a Libyan, has diabetes, as do about half of her many aunts and uncles.

“I walked out of the class and asked Dr. Cuadros, ‘Can we do this in Libya?’ “ Elkabti relates. Do some research, the professor told her.

Elkabti got to work and within an hour found Ethan Chorin, who earned his Ph.D. at Berkeley in 2000, served in the U.S. diplomatic corps in Libya from 2004 to 2006 and has published a book about the recent Libyan revolution. He founded the not-for-profit Avicenna Group in 2011 with a Libyan-American colleague to catalyze health-related partnerships between Libyan organizations and U.S. universities. Traveling back and forth between Benghazi and Berkeley, he looked for ways to involve Berkeley in Libya’s reconstruction efforts.

“I shot Ethan an email, and within hours we were talking about how to make this happen,” Elkabti says. The Berkeley-Libya retinopathy project was off and running.

Diabetes-related retinopathy is one of the leading causes of blindness in Libya — as well as in the United States and in much of the world. EyePACS has brought retinal screenings to poor and medically underserved areas from California’s Central Valley to Peru, and the Libyan retinopathy project extends the concept to politically unstable and dangerous regions.

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New organ transplant strategy aims to better prevent rejection


UCSF approach might end lifelong drug treatment.

Qizhi Tang, UC San Francisco

Organ-transplant recipients often reject donated organs, but a new, two-pronged strategy developed by UC San Francisco researchers to specifically weaken immune responses that target transplanted tissue has shown promise in controlled experiments on mice.

The hope is that using this novel treatment strategy at the time of transplantation surgery could spare patients from lifelong immunosuppressive treatments and their side effects. The approach might also be used to treat autoimmune diseases such as type 1 diabetes, the researchers said. The study is published and commented upon in a recent issue of American Journal of Transplantation.

The study was conducted in mouse studies of islet-cell transplantation — a procedure used to restore insulin secretion and control over glucose levels in the blood in patients with life-threatening diabetes. The treatment allowed more than 70 percent of mice to accept transplants without requiring any long-term treatment with immunosuppressive drugs.

The approach, led by Diabetes Center member Qizhi Tang, Ph.D., involved using cells from donors to activate immune cells called donor-reactive effector T cells. The researchers then gave the mice a drug called cyclophosphamide, known to specifically kill activated cells.

Up to 80 percent of the donor-reactive effector T cells, which play a major role in transplant rejection, were eliminated by this treatment. However, that procedure alone did not prolong survival of transplanted tissue.

That required a second step: Some of the mice also received cell therapy — an expanded population of cells called TREGs that quell immune activity. Seventy percent to 80 percent of these mice accepted the transplants, without requiring any long-term immunosuppressive drugs.

Significantly, when the cell therapy was used only in those cells that specifically target donor tissue, only one-fifth as many cells were needed to prevent transplant rejection, the UCSF researchers found. The bigger bang per cell may bode well for clinical protocols, Tang suggested.

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Study represents important step toward a cure for type 1 diabetes


Scientists reprogram skin cells into insulin-producing pancreas cells.

Sheng Ding

A cure for type 1 diabetes has long eluded even the top experts. Not because they do not know what must be done—but because the tools did not exist to do it. But now scientists in the laboratory of Gladstone Institutes’ investigator Sheng Ding, M.D., Ph.D., harnessing the power of regenerative medicine, have developed a technique in animal models that could replenish the very cells destroyed by the disease. The team’s findings, published online today (Feb. 6) in the journal Cell Stem Cell, are an important step towards freeing patients from the life-long injections that characterize this devastating disease.

Type 1 diabetes, which usually manifests during childhood, is caused by the destruction of beta-cells (ß-cells). ß-cells are a type of cell that normally resides in the pancreas and produces a hormone called insulin. Without insulin, the body’s organs have difficulty absorbing sugars, such as glucose, from the blood. Once a death sentence, the disease can now be managed with regular glucose monitoring and insulin injections. A more permanent solution, however, would be to replace the missing ß-cells. But these cells are hard to come by, so researchers have looked towards stem cell technology as a way to make them.

“The power of regenerative medicine is that it can potentially provide an unlimited source of functional, insulin-producing ß-cells that can then be transplanted into the patient,” said Ding, who is also a professor at UC San Francisco, with which Gladstone is affiliated. “But previous attempts to produce large quantities of healthy ß-cells — and to develop a workable delivery system — have not been entirely successful. So we took a somewhat different approach.”

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Resetting the metabolic clock


Insight into mammalian circadian rhythms could lead to therapies for obesity, diabetes.

Circadian rhythms are affected by things like travel over time zones, diet and light exposure. (Illustration by Peter Allen)

Circadian rhythms are affected by things like travel over time zones, diet and light exposure.

We’ve all heard about circadian rhythm, the roughly 24-hour oscillations of biological processes that occur in many living organisms. Yet for all its influence in many aspects of our lives — from sleep to immunity and, particularly, metabolism — relatively little is understood about the mammalian circadian rhythm and the interlocking processes that comprise this complex biological clock.

Through intensive analysis and computer modeling, researchers at UC Santa Barbara have gained insight into factors that affect these oscillations, with results that could lend themselves to circadian regulation and pharmacological control. Their work appears in the early edition of the Proceedings of the National Academy of Sciences.

“Our group has been fascinated with circadian rhythms for over 10 years now, as they represent a marvelous example of robust control at the molecular scale in nature,” said Frank Doyle, chair of UCSB’s Department of Chemical Engineering and the principal investigator for the UCSB team. “We are constantly amazed by the mechanisms that nature uses to control these clocks, and we seek to unravel their principles for engineering applications as well as shed light on the underlying cellular mechanisms for medical purposes.”

“Focus is often given to metabolism, cell division and other generic cell processes, but circadian oscillations are just as central to how life is organized,” said Peter St. John, a researcher in the Department of Chemical Engineering and lead author of the study.

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