Findings have important implications for public as well as health care providers.

Christopher Saigal, UCLA

The number of Americans suffering from kidney stones between 2007 and 2010 nearly doubled from 1994, according to a new study by researchers at UCLA and the RAND Corp.

“While we expected the prevalence of kidney stones to increase, the size of the increase was surprising,” said Dr. Charles D. Scales Jr., a Robert Wood Johnson Foundation/U.S. Department of Veterans Affairs Clinical Scholar in the departments of urology and medicine at the David Geffen School of Medicine at UCLA. “Our findings also suggested that the increase is due, in large part, to the increase in obesity and diabetes among Americans.”

The study, “The Prevalence of Kidney Stones in the United States” is being presented today (May 23) at the 2012 meeting of the American Urological Association in Atlanta and will appear in the July print edition of the peer-reviewed journal European Urology.

This is one of the first studies to examine new data from the National Health and Nutrition Examination Survey (NHANES) that was collected from 2007 to 2010. NHANES is a program of studies within the Centers for Disease Control and Prevention to assess the health and nutritional status of adults and children in the U.S.

Scales and his colleagues reviewed responses from 12,110 individuals and found that between 2007 and 2010, 8.8 percent of the U.S. population had a kidney stone — one out of every 11 people. In 1994, the rate was one in 20. (No data about the national prevalence of kidney stones in the U.S. were collected between 1994 and 2007.)

Because NHANES also asks about other health conditions and includes measurements of height and weight, the researchers were able to identify associations between kidney stones and other health conditions. The results suggest that obesity, diabetes and gout all increase the risk of kidney stones.

While the national obesity rate was 23 percent in 1994, more than a third of all American adults are obese today, according to the Centers for Disease Control and Prevention.

The authors assert that these findings have important implications for the public, as well as health care providers.

“People should consider the increased risk of kidney stones as another reason to maintain a healthy lifestyle and body weight,” said the study’s senior author, Dr. Christopher S. Saigal, principal investigator within RAND Health for the Urologic Diseases in America project and associate professor of urology at the David Geffen School of Medicine at UCLA. “But physicians need to rethink how to treat and, more importantly, prevent kidney stones.”

Currently, the primary approach to treating patients is to focus on those who already are suffering from kidney stones. Yet helping patients maintain a healthy diet and body weight can reduce the number of patients with kidney stones.

“Imagine that we only treated people with heart disease when they had chest pain or heart attacks and did not help manage risk factors like smoking, high cholesterol or high blood pressure,” Scales said. “This is how we currently treat people with kidney stones. We know the risk factors for kidney stones, but treatment is directed towards patients with stones that cause pain, infection or blockage of a kidney rather than helping patients to prevent kidney stones in the first place.”

In an accompanying editorial that will also appear in the journal, Dr. Brian Matlaga, associate professor of urology at Johns Hopkins University School of Medicine, writes that the cost of care for this disease is enormous, and there is no indication that the coming years will see any improvement in this trend. He also warns that, since approximately 10 percent of the population has kidney stones, a greater emphasis on prevention is imperative.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (N01-DK70003), as part of the Urologic Diseases in America project based at UCLA and RAND.

The Robert Wood Johnson Foundation Clinical Scholars program has fostered the development of physicians who are leading the transformation of health care in the United States through positions in academic medicine, public health and other leadership roles. Through the program, future leaders learn to conduct innovative research and work with communities, organizations, practitioners and policymakers on issues important to the health and well-being of all Americans. This program is supported, in part, through collaboration with the U.S. Department of Veterans Affairs.

UC San Diego nutrition experts launch yearlong study of participants with Type 2 diabetes.

Cheryl Rock, UC San Diego

Diabetes affects nearly 24 million people in the United States, most with Type 2 diabetes, a disease which is often coupled with obesity. Concerned by the increasing number of overweight Americans, nutrition experts with the UC San Diego School of Medicine are launching Take Charge, a research study analyzing the effectiveness of a commercial weight-loss program on participants with Type 2 diabetes who have a BMI of 25 – 45.

“We know that commercial weight loss programs can contribute to weight loss. Now we ask if they can have an impact on diabetes,” said Cheryl Rock, Ph.D., R.D., professor in the Department of Family and Preventive Medicine at the UC San Diego School of Medicine. “We want to find out if participants using a weight loss program do better than those who receive individualized dietary counseling with a registered dietitian.”

Rock and her team will work with primary care physicians throughout the San Diego community to enlist potential participants. “This is about the health of our entire community,” said Rock. “The problem of obesity is so great in that we need help on all fronts: medical, surgical and pharmaceutical. And we want to know if science-based commercial weight loss programs can contribute to solving this national problem as well.”

Take Charge participants must:

• Be 18 years old or older
• Be overweight
• Have Type 2 diabetes
• Be willing to participate for one year
• Otherwise be in generally good physical and mental health
• Agree to take part in the diet, exercise and lifestyle counseling program

Participants will be randomly assigned to one of three groups:

• Group one will receive dietary counseling, including menu planning and exercise advice from a registered dietitian.
• The other two groups will receive dietary counseling at a commercial facility and receive prepackaged meals coinciding with the assigned diet.
• All study participants will receive follow-up phone calls and/or emails from the study coordinator every few weeks throughout the course of the study.
• In addition, the investigators want to look at the effects of treatment on:
  • Feelings and quality of life
  • Waist circumference
  • Cardiovascular fitness

The costs of all study procedures, examinations, and medical care that may be delivered as part of this study will be provided at no cost. Participants will be compensated for travel-related costs.  This study is funded by Jenny Craig Inc. For more information on participation, please contact study coordinator, Angela Leone, M.S., R.D., UC San Diego Moores Cancer Center, (858) 822-4792 or AFLeone@ucsd.edu.

UC San Diego explores complex interactions of lipids, inflammation in insulin resistance.

Christopher Glass, UC San Diego

In the online May 2 issue of the journal Cell Metabolism, researchers at the UC San Diego School of Medicine publish three distinct articles exploring:

• the complex interactions of lipids and inflammation in insulin resistance
• the roles of omega 3 fatty acids and a particular gene in fighting inflammation
• how elevated levels of a particular protein might delay the muscle-destroying effects of amyotrophic lateral sclerosis.

Type 2 diabetes has reached epidemic proportions around the world, fueled in large part by the equally alarming expansion of obesity as a global health problem. But while it’s well-known that obesity is the most common cause of insulin resistance – the primary metabolic abnormality in type 2 diabetes – researchers have only recently begun to effectively parse the underlying, complicated relationships between lipids (fats and related molecules essential to cell structure and function) and chronic tissue inflammation (a key cause of obesity-induced insulin resistance).

In a wide-ranging perspective article published in Cell Metabolism, Christopher K. Glass, M.D., Ph.D., a professor in the departments of cellular and molecular medicine, and medicine at the UC San Diego, and Jerrold M. Olefsky, M.D., associate dean for scientific affairs and distinguished professor of medicine at UC San Diego, survey where the science stands, describing, for example, the pro-inflammatory effects of saturated fatty acids and the anti-inflammatory benefits of omega 3 fatty acids. They also discuss how inflammation impacts lipid metabolism at the cellular, tissue, organ and whole-body levels.

In a second, related article, Olefsky and colleague Da Young Oh, an assistant project scientist, discuss the critical role of a gene called GPR120 in inhibiting pro-inflammatory macrophages while simultaneously boosting the anti-inflammatory benefits of omega 3 fatty acids. They argue that new research highlights the importance of GPR120 as an attractive target for new drugs that could increase insulin sensitivity and, perhaps, have anti-obesity effects as well.

Finally, Don W. Cleveland, Ph.D., professor and chair of the Department of Cellular and Molecular Medicine and head of the Laboratory of Cell Biology at the Ludwig Institute for Cancer Research at UC San Diego and colleagues report the effects of elevated levels of a gene- regulating protein in mouse cells afflicted by a form of amyotrophic lateral sclerosis or ALS.

In humans, ALS is a progressive, adult-onset neurodegenerative disorder characterized by selective motor neuron and muscle loss that ultimately results in fatal paralysis. Among the key players in muscle function is a transcriptional activator protein called PGC-1alpha, which helps enhance various aspects of muscle cell function, including metabolism and mitochondrial biogenesis.

Cleveland and colleagues report that elevated levels of PGC-1alpha in the muscles of a mouse model of inherited ALS helps maintain health and function, though it does not extend survival time. The researchers suggest that increasing PCG-1alpha activity in muscle could be a new and attractive therapeutic target for maintaining, improving and extending physical abilities in ALS patients.

UCLA researcher: Dietary intervention during early life can have long lasting effects.

Sherin Devaskar, UCLA

Babies who are born small have a tendency to put on weight during childhood and adolescence if allowed free access to calories. However, a new animal model study at UCLA found when small babies were placed on a diet of moderately regulated calories during infancy, the propensity of becoming obese decreased.

Because this is an early study, UCLA researchers do not recommend that mothers of low-birth weight infants start restricting their child’s nutrition and suggest they consult with their child’s pediatrician regarding any feeding questions.

Previous studies have shown that growth restriction before birth may cause lasting changes of genes in certain insulin-sensitive organs like the pancreas, liver and skeletal muscle. Before birth, these changes may help the malnourished fetus use all available nutrients. However, after birth these changes may contribute to health problems such as obesity and diabetes.

“This study shows that if we match the level of caloric consumption after birth to the same level that the growth-restricted baby received in the womb, it results in a lean body type. However, if there is a mismatch where the baby is growth-restricted at birth but exposed to plenty of calories after birth, then that leads to obesity,” said the lead author, Dr. Sherin Devaskar, professor of pediatrics and executive chair of the department of pediatrics at Mattel Children’s Hospital UCLA. ”While many trials that include exercise and various drug therapies have tried to reverse the tendency of low birth weight babies becoming obese, we have shown that a dietary intervention during early life can have long lasting effects into childhood, adolescence and adult life.”

The study appears in the June issue of the journal Diabetes and is currently available online.

About 10 percent of babies in the United States are born small, defined as less than the 10th percentile by weight for a given gestation period, said the study’s first author, Dr. Meena Garg, professor of pediatrics and a neonatologist and medical director of the neonatal intensive care unit at Mattel Children’s Hospital UCLA. She added that some organizations define low birth weight as less than 2,500 grams or 5 pounds, 5 ounces at term.

Low birth weight can be caused by malnutrition due to a mother’s homelessness or hunger or her desire not to gain too much weight during pregnancy. Additional causes include illness or infection, a reduction in placental blood, smoking or use of alcohol or drugs during pregnancy.

To conduct the study, researchers used rodent animal models and simulated a reduced calorie scenario during pregnancy. The results showed that low-birth weight offspring exposed to moderately tempered caloric intake during infancy and childhood resulted in lean and physically active adults related to high energy expenditure, as opposed to unrestricted intake of calories, which resulted in inactive and obese adults due to reduced energy expenditure. The authors concluded that early life dietary interventions have far reaching effects on the adult state.

Future studies will follow this study over the stages of aging to see if early regulation of calorie intake reverses diabetes and obesity while aging.

“This is an early pre-clinical trial that first needs to be tested in clinical trials before any form of guidelines can be developed,” Devaskar said. “More importantly, we must make sure that control of caloric intake during infancy and childhood does not have any unintended side effects before taking on clinical trials. More research is required to ensure that these metabolic advantages will persist later in life.”

The study was funded by the National Institute of Child Health and Human Development.

In addition to Devaskar and Garg, the study was conducted by a team of UCLA researchers including Manikkavasagar Thamotharan, Yun Dai, Shanthie Thamotharan, Bo Chul Shin and David Stout.

The authors have no financial ties to disclose.

Discovery may lead to new strategies to address insulin resistance.

Katerina Akassoglou

Scientists at the Gladstone Institutes have discovered a key protein that regulates insulin resistance — the diminished ability of cells to respond to the action of insulin and which sets the stage for the development of the most common form of diabetes.

This breakthrough points to a new way to potentially treat or forestall type 2 diabetes, a rapidly growing global health problem.

In a paper being published online this week in the Proceedings of the National Academy of Sciences, researchers in the laboratory of Gladstone Investigator Katerina Akassoglou, Ph.D., describe an unexpected role of the p75 neurotrophin receptor in controlling how the body processes sugar. Called p75NTR, this receptor protein is usually associated with functions in neurons.

“We identified that p75NTR is a unique player in glucose metabolism,” said Akassoglou, who is also an associate professor of neurology at UCSF, which  is affiliated with the Gladstone Institutes. “Therapies targeted at p75NTR may represent a new therapeutic approach for diabetes.”

The pancreas makes a hormone called insulin that processes glucose, moving it from the bloodstream into the body’s cells where it is used for energy. Insulin resistance is a key feature of type 2 diabetes, in which glucose builds up in the bloodstream and the body’s cells are unable to function properly. According to the Centers for Disease Control and Prevention, more than 20 million Americans have type 2 diabetes.

“Type 2 diabetes has become a very serious health problem and it is increasing at an alarming rate,” said Lennart Mucke, M.D., who directs the institute in which the research was conducted. “These findings provide an important new avenue for developing better therapies to combat this deadly disease — the seventh leading cause of death in the United States.”

Complex signaling interactions between several different types of tissue — including fat, liver, muscle and brain — regulate glucose metabolism. Because p75NTR is found in fat and muscle tissue and participates in many important functions in the cell, Gladstone scientists hypothesized that p75NTR might also help to regulate glucose metabolism.

To study this, the researchers used mice that lacked the genes for p75NTR. They compared these mice to normal mice and discovered that those lacking p75NTR were more responsive to insulin when fed a normal diet. Second, they used some molecular biology tricks to block the action of the p75NTR protein in fat cells. This also resulted in increased glucose absorption in response to insulin. In contrast, when they caused the fat cells to make more p75NTR, glucose absorption was reduced.  Additionally, the researchers found that another important regulatory molecule, Rab5, played a key role in p75NTR’s impact on metabolism.

“Importantly, regulation by p75NTR enhanced insulin’s effectiveness in normal lean mice on a normal diet,” said Bernat Baeza-Raja, Ph.D., postdoctoral fellow and lead author of the study. “Because these mice already process glucose efficiently, the actions of p75NTR on glucose transport indicate a direct role of this protein in the regulation of glucose metabolism.”

“Our studies of p75NTR’s unanticipated role in regulating glucose metabolism suggest a new target for drug therapies,” said Akassoglou. “Future work is needed to test whether this finding may translate into a potential treatment.”

This study was a collaborative work between scientists at Gladstone, UC San Diego, the University of Michigan and the University of Houston. Other scientists who participated in this research at Gladstone include Natacha Le Moan, Ph.D.; Christian Schachtrup, Ph.D.; Dimitrios Davalos, Ph.D.; and Eirini Vagena. Jerrold Olefsky, Ph.D., and Pingping Li, Ph.D., at UC San Diego were co-senior and co-first authors, respectively. Funding was provided by a variety of sources, including the National Institutes of Health, the UCSF Liver Center and Diabetes and Endocrinology Center and the R. A. Welch Foundation.

Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases. Gladstone is affiliated with the University of California, San Francisco.

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.

UCSF identifies new target against obesity involving brown fat.

In the war against obesity, one’s own fat cells may seem an unlikely ally, but new research from the University of California, San Francisco, suggests ordinary fat cells can be re-engineered to burn calories.

While investigating how a common drug given to people with diabetes works in mice, a UCSF team discovered that a protein called PRDM16, found in both men and mice, can throw a switch on fat cells, converting them from ordinary calorie-storing white fat cells into calorie-burning brown fat cells.

Shingo Kajimura, UC San Francisco

This discovery makes PRDM16 a possible target for future obesity drugs. Compounds that promote the action of this protein may help people burn calories faster. Though they would have to prove safe and effective in the clinic, such compounds would represent a completely different approach to weight loss. Existing diet drugs aim to restrict the intake of calories — by blocking the absorption of fat in the gut, for instance, or by decreasing appetite.

“If you think about the energy balance, the other way to tackle obesity is through energy expenditure,” said Shingo Kajimura, Ph.D., who led the research in the UCSF Diabetes Center and the Department of Cell & Tissue Biology in the UCSF School of Dentistry. The work is published this week in the journal Cell Metabolism.

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Improvement seen in patients with heart failure and type 2 diabetes in initial study.

Francisco Villarreal, UC San Diego

A small clinical trial led by researchers at UC San Diego School of Medicine and VA San Diego Healthcare System (VASDHS) found that patients with advanced heart failure and type 2 diabetes showed improved mitochondrial structure after three months of treatment with epicatechin-enriched cocoa. Epicatechin is a flavonoid found in dark chocolate.

The results of this initial study has led to the implementation of larger, placebo-controlled clinical trial at UC San Diego School of Medicine and VASDHS to assess if patients with heart failure and diabetes show improvement in their exercise capacity when treated with epicatechin-rich cocoa.

The study published this week by the journal Clinical and Translational Science looked at five profoundly ill patients with major damage to skeletal muscle mitochondria. Mitochondria are structures responsible for most of the energy produced in cells. These “fuel cells” are dysfunctional as a result of both type 2 diabetes and heart failure, leading to abnormalities in skeletal muscle. In patients with heart failure and diabetes abnormalities in both the heart and skeletal muscle result in impaired functional capacity. These patients often complain of shortness of breath, lack of energy and have difficulty walking even short distances.

The trial participants consumed dark chocolate bars and a beverage with a total epicatechin content of approximately 100 mg per day for three months. Biopsies of skeletal muscle were conducted before and after treatment. After the three-month treatment, the researchers looked at changes in mitochondria volume and the abundance of cristae, which are internal compartments of mitochondria that are necessary for efficient function of the mitochondria, and measurable by electron microscopy.

“The cristae had been severely damaged and decreased in quantity in these patients,” said one of the senior investigators, Francisco J. Villarreal, M.D., Ph.D., of UC San Diego’s Department of Medicine’s Division of Cardiology. “After three months, we saw recovery — cristae numbers back toward normal levels and increases in several molecular indicators involved in new mitochondria production.”

The results, which mimicked earlier studies showing improvement in skeletal and heart muscle function in animal models after treatment with epicatechin, were promising enough to prompt the larger study.

The principal investigator of this trial was Pam R. Taub, M.D., assistant professor of medicine at UC San Diego and the VA San Diego Healthcare System. Taub will be leading the new clinical trial at UC San Diego that will enroll normal sedentary subjects as well as patients with heart failure/diabetes who will be treated with placebo, or epicatechin-rich chocolate.

Patients who would like more information about the clinical trial can call (858) 552-8585, extension 3866.

Additional contributors to the published study include Israel Ramirez-Sanchez, Ph.D., Theodore P. Ciaraldi, Ph.D., Alan S. Maisel, M.D., and Robert R. Henry, M.D., UC San Diego School of Medicine and VA San Diego Health System; Guy Perkins, Ph.D., Anne N. Murphy, Ph.D., Robert Naviaux, M.D., Ph.D., and Michael Hogan, Ph.D., UC San Diego School of Medicine; and Guillermo Ceballos, M.D., Ph.D., Escuela Superior de Medicina del Instituto Politécnico Nacional, Mexico City.

The study was supported in part by grants from the National Institutes of Health, American College of Cardiology and The Hershey Co.

UC Davis research highlights role of elevated levels of Toll-like receptors on cells.

Ishwarlal Jialal, UC Davis

UC Davis scientists have uncovered a key suspect in the destructive inflammation that underlies heart disease and diabetes. The new research shows elevated levels of a receptor present on leucocytes of the innate immune response in people at risk for these chronic diseases. The receptors are the body’s first line of defense against infectious invaders, and they trigger a rush of cytokines, the body’s aggressive immune soldiers, into the bloodstream.

The research, published today (Feb. 22) in the journal Diabetes Care, studied individuals diagnosed with metabolic syndrome — a cluster of cardio-metabolic risk factors linked to many life-threatening diseases. Metabolic syndrome is found in about a third of American adults and people in other industrialized countries.

The syndrome is a high-risk obesity state as previously shown by diabetes expert Ishwarlal Jialal and his team at the UC Davis Medical Center. It increases the risk of developing diabetes at least five-fold and heart disease by two- to four-fold. Jialal, professor of pathology and laboratory medicine at UC Davis Health System, also led the new study.

The receptors, or sensors, on cells are called Toll-like receptors (TLRs), and the Nobel Prize was awarded last year for discoveries that showed they initiate the swift innate immune response to infections. But the inflammation they trigger can also be harmful. In mice it has been shown that two TLRs — TLR2 AND TLR4 — are important in the development of both diabetes and heart disease.

These receptors are present in many cells, but they are most abundant on monocytes, a type of white blood cell that plays a central role in the inflammation response to invading microbes. They can be triggered by pathogen products or signals from dying cells and saturated fatty acid.

The UC Davis research focused on TLR2 and TLR4. For the study, researchers evaluated 90 individuals between the ages of 21 and 70, of whom 49 had at least three features characteristic of metabolic syndrome. These included hypertension, low HDL-cholesterol, high triglycerides and obesity, as evidenced by increased waist circumference, or a glucose level between 101-125 mg/dl but not indicative of diabetes. Members of the control group had no more than two such markers. People with atherosclerosis, diabetes, inflammatory or malignant disease, and other disorders were excluded to study the receptor function without confounding variables, and to gain insights into nascent or early metabolic syndrome prior to complications.

Comparisons of the blood of participants from both groups showed that the metabolic syndrome group exhibited significantly higher levels of both messenger RNA and cell-surface receptor proteins TLR2 and TLR4, increased levels of the master switch of inflammation in the nucleus, and a much higher concentration of immune soldiers in the blood, such as cytokines, that create inflammation.

All of these abnormalities were independent of obesity, suggesting they are due to the metabolic-syndrome environment. The levels of both free fatty acids and the product of gram-negative bacteria endotoxin also were increased in the blood of individuals with metabolic syndrome at least two- and three-fold respectively, and explained in part the TLR4 increase.

The research suggests that suppressing TLR activity with weight loss and with diet, exercise and drugs targeted specifically at these receptors, might prove effective in treating heart disease, diabetes and other conditions linked to metabolic syndrome.

Jialal pointed out that not all obese people suffer from the constellation of symptoms that make up metabolic syndrome, and in fact, about 30 percent of obese people are at low risk for metabolic complications, according to one key study. But since research shows increased inflammation in obese people, the Toll-like receptor and monocyte findings may help define individuals at high risk for obesity.

Jialal’s research group reported last year that monocytes and related macrophages were present in the fat of individuals with metabolic syndrome and that their fat was more inflamed. The new finding shows that the Toll-like sentinel proteins might be directing an increase in this activity, and that the inflammatory agents are making it into the bloodstream, from where they can go to any part of the body, including fat, liver and heart.

The research is funded by the American Diabetes Association.

UC Davis Health System is improving lives and transforming health care by providing excellent patient care, conducting groundbreaking research, fostering innovative, interprofessional education and creating dynamic, productive partnerships with the community. The academic health system includes one of the country’s best medical schools, a 631-bed acute-care teaching hospital, an 800-member physician’s practice group and the new Betty Irene Moore School of Nursing. It is home to a National Cancer Institute-designated cancer center, an international neurodevelopmental institute, a stem cell institute and a comprehensive children’s hospital. Other nationally prominent centers focus on advancing telemedicine, improving vascular care, eliminating health disparities and translating research findings into new treatments for patients. Together, they make UC Davis a hub of innovation that is transforming health for all. For more information, visit healthsystem.ucdavis.edu.

UCLA study: Tool doesn’t adequately evaluate services that determine quality of diabetes care in community health centers.

Robin Clarke, UCLA

On the health front, the poor often have at least two things going against them: a lack of insurance and chronic illnesses, of which diabetes is among the most common.

The federal Affordable Care Act would expand the capacity of the nation’s 8,000 community health centers to provide care for low-income, largely minority patients — from the current 20 million to about 40 million by 2015. The federal government is also trying to ensure that these community health centers deliver high-quality primary care, including diabetes care.

A crucial part of this is the implementation of what is known as the “patient-centered medical home model,” which provides comprehensive, coordinated care among patients, their physicians and, sometimes, family members through the use of registries, information technology and other resources. It is intended to ensure that patients receive care on a continuous basis — rather than just during periodic visits to the doctor’s office, for example.

The assessment tool used by federal government programs to measure whether a community health center is functioning as a “medical home” was developed by the nonprofit National Committee for Quality Assurance (NCQA). But, according to a new UCLA study, there’s a problem: The NCQA tool doesn’t adequately evaluate the services that determine the quality of diabetes care in community health centers. In fact, the study found, there is no relation between how well a health center scored on the NCQA assessment and the quality of diabetes care it provided.

The study is being released today (Feb. 15) as a “Web first” publication by the journal Health Affairs and will appear in the journal’s March print issue.

“The major issue here is that the NCQA assessment tool was developed based on evidence of what worked for private primary-care practices that delivered care to insured patients,” said lead author Dr. Robin Clarke, a physician in the Robert Wood Johnson Foundation Clinical Scholars program in the division of general internal medicine and health services research at the David Geffen School of Medicine at UCLA. “Because we have limited experience in applying the NCQA tool to community health centers, there is a question of what effective, patient-centered care for low-income patients actually entails.”

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UCSF researchers say societal control of sugar needed, similar to alcohol, tobacco.

Sugar should be controlled like alcohol and tobacco to protect public health, according to a team of UCSF researchers, who maintain in a new report that sugar is fueling a global obesity pandemic, contributing to 35 million deaths annually worldwide from non-communicable diseases like diabetes, heart disease and cancer.

Non-communicable diseases now pose a greater health burden worldwide than infectious diseases, according to the United Nations. In the United States, 75 percent of health care dollars are spent treating these diseases and their associated disabilities.

In the Feb. 2 issue of Nature, Robert Lustig, M.D., Laura Schmidt, Ph.D., M.S.W., M.P.H., and Claire Brindis, D.P.H., colleagues at the University of California, San Francisco, argue that sugar’s potential for abuse, coupled with its toxicity and pervasiveness in the Western diet, make it a primary culprit of this worldwide health crisis.

This partnership of scientists trained in endocrinology, sociology and public health took a new look at the accumulating scientific evidence on sugar. Such interdisciplinary liaisons underscore the power of academic health sciences institutions like UCSF.

Sugar, they argue, is far from just “empty calories” that make people fat. At the levels consumed by most Americans, sugar changes metabolism, raises blood pressure, critically alters the signaling of hormones and causes significant damage to the liver — the least understood of sugar’s damages. These health hazards largely mirror the effects of drinking too much alcohol, which they point out in their commentary is the distillation of sugar.

Worldwide consumption of sugar has tripled during the past 50 years and is viewed as a key cause of the obesity epidemic. But obesity, Lustig, Schmidt and Brindis argue, may just be a marker for the damage caused by the toxic effects of too much sugar. This would help explain why 40 percent of people with metabolic syndrome — the key metabolic changes that lead to diabetes, heart disease and cancer — are not clinically obese.

“As long as the public thinks that sugar is just ‘empty calories,’ we have no chance in solving this,” said Lustig, a professor of pediatrics in the division of endocrinology at the UCSF Benioff Children’s Hospital and director of the Weight Assessment for Teen and Child Health (WATCH) Program at UCSF.

“There are good calories and bad calories, just as there are good fats and bad fats, good amino acids and bad amino acids, good carbohydrates and bad carbohydrates,” Lustig said. “But sugar is toxic beyond its calories.”

Limiting the consumption of sugar has challenges beyond educating people about its potential toxicity. “We recognize that there are cultural and celebratory aspects of sugar,” said Brindis, director of UCSF’s Philip R. Lee Institute for Health Policy Studies (IHPS). “Changing these patterns is very complicated.”

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UC Irvine center explores, extols health benefits of exercise in childhood.

Dan Cooper, UC Irvine

Dr. Dan Cooper believes that exercise can be the best medicine — so much so that he’s studying how specifically designed exercise programs for at-risk kids can help curb excessive weight gain, fight diseases and foster long-term fitness.

With childhood obesity and asthma emerging as national health crises, Cooper in 2006 founded UC Irvine’s Pediatric Exercise Research Center, and over the past six years, it has shed light on the full benefits of physical activity.

At any one time, PERC hosts 15 to 20 studies of how — and how much — exercise works to avert type 2 diabetes, limit asthma attacks, thwart arthritis, prevent cancer, encourage mineralization in growing bones, and improve the quality of life for kids with chronic diseases and congenital disorders.

“Our purpose is to recognize the importance of exercise for health and growth in children,” says Cooper, professor and chair of pediatrics at UCI and director of the Institute for Clinical & Translational Science, which supports PERC efforts. “We’re one of the few centers in the country to focus on this crucial issue.”

He and PERC’s associate director, gymnast Shlomit Aizik, maintain that exercise is necessary not only for good childhood health but also to prevent later-in-life maladies such as heart disease and stroke.

Cooper was one of the principal investigators for the nationwide Healthy study, which involved healthier cafeteria choices, longer and more intense periods of physical activity, and robust in-school education programs to lower rates of obesity and other risk factors for type 2 diabetes.

Besides its role in overall fitness, exercise also triggers biochemical mechanisms that activate anti-inflammatory cells and important growth factors, Aizik says.

PERC-supported research on these biochemical mechanisms opened the door to understanding the positive influence of physical activity on immune diseases — most commonly asthma and, to a lesser extent, arthritis, which is increasingly seen in obese children — while addressing a pressing question.

“How much exercise is too much?” Cooper says. “Too much can actually worsen these conditions. The challenge is determining the right ‘dose’ of exercise to achieve anti-inflammatory benefits without causing future harm. PE teachers are not trained for this, so we’re establishing programs to help schools properly integrate the correct amount of exercise.”

PERC researchers are also probing the impact of physical activity during key stages of child development. For example, studies show that diet and exercise are linked to proper mineralization in growing bones, which can stave off osteoporosis in middle and old age.

A PERC group is currently looking at the effects of exercise on infants born two to three months early, missing out on a phase of fetal life marked by lots of body-conditioning physical movement. “This is lost when babies are born prematurely, interfering with a critical growth period,” Cooper says.

His team has created an activity program to offset this deficit. It starts, he says, with passive manipulation of a newborn’s arms and legs and progresses over 12 months to include such motions as head lifting and crawling. After a year, researchers will assess the influence of the exercise on body composition, bone mineralization and additional developmental markers.

Another PERC effort — led by Aizik — seeks to increase physical activity among kids with congenital conditions. College students are being trained to engage spina bifida patients at Miller Children’s Hospital Long Beach in exercise.

“Youngsters with disabilities rarely get enough physical activity,” Aizik says. “And studies show that it improves and extends the quality of life for these children. We want to measure the psychological and physiological results of this mentor-based program to see how we can incorporate an appropriate amount of exercise into their lives.”

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Alliance is UCSF’s third collaboration with Sanofi.

Matthias Hebrok, UC San Francisco

The University of California, San Francisco, has signed an alliance with international pharmaceutical company Sanofi (EURONEXT: SAN and NYSE: SNY) to share expertise in diabetes research and identify drug targets that could lead to new therapies for both type 1 and type 2 diabetes.

The $3.1 million collaboration will bring together scientists in three UCSF labs with deep understanding of the biology of beta cells – insulin-producing cells that are destroyed in type 1 diabetes and often produce too little insulin in type 2 – with Sanofi researchers who are experienced in developing potential drug candidates into actual therapies.

“This is a true partnership between scientists with very different strengths,” said Matthias Hebrok, Ph.D., director of the UCSF Diabetes Center. “UCSF is known for its deep understanding of the underlying biology of diabetes, while Sanofi has great expertise in screening compounds, identifying which molecules have potential, and moving them along to develop a new drug. Such an endeavor is almost impossible to accomplish in a single academic laboratory. Thus, both partners profit from the expertise of the other group.”

The alliance is the university’s third collaboration with Sanofi, alongside brain trauma and oncology research launched last year, since the two signed a master agreement in January 2011 to work together in translating academic science into potential new therapies. Master agreements lay out the fundamental terms of research collaborations, align with the University’s academic mission including broad publication rights, and form part of a core strategy for the UCSF Office of Innovation, Technology and Alliances to expedite that “bench-to-bedside” research.

This also is the first collaboration of its kind for the UCSF Diabetes Center, extending beyond simpler, funded-research agreements to create a two-way partnership in which scientists on both sides contribute technology and expertise to identify drug targets and test their potential.

“Sanofi is pleased to collaborate with the Diabetes Center at UCSF to combine expertise in employing new technologies for the development of innovative diabetes therapies,” said Pierre Chancel, senior vice president in the Diabetes Division at Sanofi. “The potential resulting drug discovery projects will supplement our integrated solutions model for diabetes management and help Sanofi continue to deliver best-in-class solutions to people living with diabetes.”

Together, the team will assess and validate potential drug targets from a UCSF library of roughly 100,000 small interference RNAs (siRNA) – molecules that play a crucial role in turning on and off genes, including the gene that produces insulin. They also will identify Sanofi compounds that might be effective in regulating those molecules, study the impact those compounds have on UCSF laboratory models of diabetes and assess their therapeutic potential.

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