Smoking, Diabetes Predict Different Forms of Peripheral Artery Disease

American Heart Association rapid access journal report

May 31, 2006 (EurekAlert) - Cigarette smoking and high cholesterol predict risk for some forms of peripheral artery disease (PAD), while diabetes predicts risk for other forms of the disease, researchers reported in a rapid access issue of Circulation: Journal of the American Heart Association.

Researchers examined risk factors for PAD progression in large blood vessels (LV-PAD) and in small blood vessels (SV-PAD). PAD is characterized by clogged arteries outside the heart or brain - most often in the legs. An estimated 8 million people in the United States have PAD.

When large leg vessels are involved, the classic symptom is painful cramping in the hips, thighs or calves that occurs during exercise and eases after a few minutes of rest. With small vessels, the feet may be cool to the touch, heal slowly when injured, and in extreme cases require amputation.

Researchers identified several risk factors that influence the evolution of LV-PAD. Smoking appeared to be the most powerful predictor that PAD would get worse.

"Smoking cessation is the most efficient way to slow the progression of PAD, along with altering cholesterol levels through diet, exercise and medication," said study lead author Victor Aboyans, M.D., Ph.D. "By highlighting and focusing preventive efforts on the risk factors, we can improve the prognosis."

Aboyans – a cardiologist and epidemiologist at the Dupuytren University Hospital in Limoges, France – conducted this study while a visiting scholar in the Department of Family and Preventive Medicine at the University of California, San Diego.

He and colleagues examined 403 men and women (average age 69) with LV-PAD and 290 with SV-PAD (average age 68) who were previously suspected of having PAD and underwent evaluation. For the current analysis, results from these initial examinations were compared with new tests performed an average of 4.6 years later.

Researchers compared blood pressure readings in the ankles and toes with those in the arms - the ankle-brachial index (ABI) and toe-brachial index (TBI). Blood pressure in the ankle that's less than 90 percent of the arm measurement indicates PAD, while toe blood pressure less than 70 percent of the arm measurement also indicates PAD.

During follow up, patients showed a significant deterioration in ABI and TBI, although some remained stable. Those suffering the steepest declines (the highest 10 percent), with at least a 0.30 decrease in ABI or 0.27 decrease in TBI, were considered to have major PAD progression. Researchers compared risk factors in these patients with those whose arteries did not narrow as significantly during follow up.

Among those with LV-PAD, current smokers were 3.2 times more likely to have major progression. Those with a high ratio of total cholesterol to high-density lipoprotein (HDL) – the good cholesterol – were also more likely to have their PAD substantially progress.

Heavy drinking (more than 21 alcoholic beverages per week) was also associated with worse LV-PAD, but was considered "borderline predictive" of PAD progression. Likewise, higher pulse pressure (the difference between the upper and lower numbers in a blood pressure reading, which indicates stiffening in major blood vessels) was a borderline predictor of progression.

Researchers analyzed several novel cardiovascular risk factors and found that high levels of Lipoprotein a, or Lp(a) – a lipid particle, and high levels of highly sensitive C-reactive protein, or hsCRP – an inflammation marker, were also predictive of greater progression of LV-PAD. However, high levels of homocysteine, previously identified as a risk factor for PAD, did not predict progression.

The only significant predictor of SV-PAD progression was diabetes.

"The most surprising result was the absence of an impact of diabetes in large vessel PAD progression," Aboyans said.

The findings point to the importance of thinking about small and large-vessel PAD separately and looking for both when assessing blood flow in the legs.

"Some patients in this study had progressive artery blockage, but the only initial evidence was in the toe," said co-author Michael H. Criqui, M.D., M.P.H., professor of medicine and professor of family and preventive medicine at the University of California, San Diego School of Medicine. "Particularly in patients with diabetes, doctors may need to measure both ABI and TBI."

The results reinforce new American College of Cardiology/American Heart Association guidelines on the management of PAD, published in Circulation in March, 2006. The guidelines recommended anti-platelet therapy – such as aspirin and cholesterol treatment with statins.

"If you have PAD and are taking low-dose aspirin and a statin, you're doing two things that are very helpful," Criqui said.

Posted by dlife at 08:48 AM | Comments (0)

dLife Spotlights Ten Who Make a Difference for People Living With Diaabetes

Leading media voice for the diabetes community shines spotlight on new faces fighting the diabetes epidemic; thousands of America’s 21 million people with diabetes name their heroes.

WESTPORT, CT., May 31, 2006--What do one of America’s most famous and influential CEOs, a comic book written by two young boys, and a basketball superstar have in common?

Answer: Diabetes and the admiration of more than 20,000 readers, listeners, and viewers of dLife, America’s leading multimedia information source for people living with diabetes. Basketball superstar Adam Morrison, business giant Lee Iacocca, and comic book authors Kamaal and Malcolm Washington were among The Annual dLife Top 10, Making a Difference in Diabetes. This marks the first year for these awards, which were based on the contributions these winners made to the diabetes community throughout 2005.

dLife’s editorial staff, which presents valuable information about diabetes through television, radio, web, and print, combined their diabetes knowledge to offer a list of nominees representing those in America who inspired, motivated and improved the lives of people with diabetes. Thousands voted online to whittle the nominee list down to the final award winners.

The runaway winner at number 1 was college basketball superstar, Adam Morrison. Morrison, projected by many to be the number 1 pick in the upcoming NBA draft, was the nation’s leading scorer during the 2005-2006 college basketball season, all the while publicly managing his diabetes by openly testing his blood sugars and injecting insulin courtside. Morrison’s public acknowledgment of his chronic disease helped make it very clear that people with diabetes can take control of their condition and not only achieve success in life, but also achieve greatness.

“Some days the sugars are up and down and your body just doesn’t feel right but it’s no excuse,” says Morrison. “You gotta just go out there and give it 110 percent, even though you don’t feel well.” Apparently this message has resonated as dramatically within the diabetes community as his athletic skills on the court have resonated within the sports community.

Internationally famous business leader Lee Iacocca was also a hit with voters. Through JoinLeeNow, the fund-raising arm of The Iacocca Foundation, founded in honor of his wife Mary Iacocca whose death was due to complications of type1 diabetes, more than $9 million was raised to support promising research for a diabetes cure.

Approaching diabetes from an entirely different direction, the two young sons of Alonzo Washington, creator/publisher of OMEGA MAN comics, followed heroically in their father’s footsteps. Kamaal (10) and Malcolm (8) were inspired to create a story about Omega Boy and Doctor Diabetes after Kamaal was diagnosed with the disease. “Kamal and his brother wanted to do something to bring more awareness to the illness,” says their dad, Alonzo Washington. “They have been begging me for years to publish one of their characters. When they told me that they wanted to use Omega Boy to address diabetes, how could I say no?” The 18-page comic has attracted interest from various media outlets as well as various diabetes organizations. Keeping the ball rolling, Kamaal plans to do a national tour to help children afflicted with the illness.

The other winners are nurse/educator KC Arnold, who distributed diabetes supplies to Hurricane Katrina victims; the Children With Diabetes quilt, a project that tells the life stories of children with diabetes; Jay Leeuwenburg and Denny Dressman, authors of the book Yes I Can! Yes You Can!, a chronicle of Jay’s struggle to balance his diabetes with his 9-year professional football career, the Asian outreach program at The Joslin Diabetes Center, a model bilingual program, Maurice Madden, whose film “The Debilitator” educates the African-American community about diabetes, Bernard Siegel, whose work on behalf of the diabetes community promotes an open debate on stem cell research and Kendall Simmons of the Super Bowl champion Pittsburgh Steelers for his work helping kids with diabetes.

“The range of winners provides some real insight into just how widely the diabetes epidemic impacts our society,” says Howard Steinberg, the CEO and Founder of LifeMed Media, parent company of dLife, who lives with type 1 diabetes. “And perhaps more importantly, the variety of winners demonstrates how people of all ages and backgrounds are learning to take control of diabetes and lead incredibly successful and satisfying lives.”

About LifeMed Media and dLife
LifeMed Media is the first multimedia healthcare communications company created to serve chronic disease populations. Its flagship venture, dLife—For Your Diabetes Life!, is the first integrated media network targeting the estimated 21 million people living with diabetes and their caregivers, families, friends, and those at risk of developing diabetes—some 80 million in all. dLife provides knowledge, insight, advice and inspiration to this group through dLifeTV, dLife.com, dLifeRadio, and dLifeConnect.

For further information please contact Tom Karlya @ 203-221-3453 or karlya@dlife.com. You can also visit our website as www.dlife.com.

Available graphics: dLife logo, Omego Boy comic book cover, Adam Morrison action shot.

Posted by dlife at 08:44 AM | Comments (0)

Novocell, JDRF Announce Partnership to Clinically Test Encapsulated Human Islets

Protocol Could Advance Islet Replacement Therapies for Patients with Type 1 Diabetes

NEW YORK, May 31, 2006 (PRNewswire) - The Juvenile Diabetes Research Foundation announced today that it has established a partnership with Novocell, Inc. an Irvine, California-based, biotechnology company, to support an on-going proof of principle phase I/II human clinical trial for Novocell's polyethylene glycol encapsulation of insulin-producing islets.

According to Richard A. Insel, MD, Executive Vice President of Research at JDRF, the Novocell partnership is an exciting opportunity to clinically evaluate one of the potential therapies to cure type 1 diabetes. "The Novocell encapsulation procedure potentially provides an approach to avoid the use of chronic immunosuppressive drugs in the islet transplant setting. We are pleased to support the clinical translation of this research that has shown promise in animal research."

Islet transplantation has shown success over the past few years in significantly improving the day-to-day life of adult patients with uncontrolled diabetes or hypoglycemic unawareness, reversing their diabetes for a period of time and lowering their insulin requirements for an extended period. But the immunosuppressive drugs needed to suppress both the alloimmune (foreign tissue rejection) and autoimmunue reactions to the transplanted islets can have significant side effects, making them inappropriate for children with diabetes.

Novocell's encapsulation technology uniformly coats donated pancreatic islets with a thin layer of biocompatible material. This coating is believed to enable implanted cells to survive subcutaneously and control glucose levels in patients with type 1 diabetes, resulting in near normal hemoglobin A1c levels without the need for life-long immunosuppression.

"Our encapsulation technology will be an essential element to implanted islet cells for the treatment of diabetes," commented Alan Lewis, Ph.D. president and CEO of Novocell. "We expect to demonstrate the safety and efficacy of encapsulated islet cells in patients through this trial."

The partnership is the latest in JDRF's innovative Industry Discovery and Development Partnership Program, in which the world's leading charitable funder of research for type 1 diabetes teams with biotechnology companies to develop drugs, therapies, and treatments for diabetes. The program supports companies -- often in collaboration with academic researchers -- to develop or test, in preclinical models or early-stage clinical trials, novel therapeutic approaches for diagnosis, prevention or treatment of type 1 diabetes or its complications.

The program includes two types of partnerships. Discovery Partnerships are intended to support early stage proof-of-concept programs, which identify mechanisms of potential therapeutics, demonstrate pre-clinical efficacy, or pilot clinical assessment of a potential therapeutic approach. Development Partnerships provide support for promising mid-stage research programs, including the advancement of a pre-clinical stage program to clinical trials, or advanced Phase II/III clinical testing of promising therapeutics.

Posted by dlife at 08:41 AM | Comments (0)

Researchers Open Door to Potential Treatments for Type 2 Diabetes

OTTAWA, May 29, 2006 (Eurekalert) – Researchers funded by the Canadian Institutes of Health Research (CIHR) and the Canadian Diabetes Association (CDA) have identified an unsuspected role of a protein named SHP-1 that could constitute a new therapeutic path against type 2 diabetes.

Under the direction of professor André Marette (Laval University), Nicole Beauchemin (McGill University), Martin Oliver (McGill University Health Centre) and Katherine Siminovitch (University of Toronto) were part of a Canadian and American team which published an article in the May issue of Nature Medicine that explains the role of SHP-1 in the control of blood glucose.

The researchers already knew that SHP-1 played a role in regulating the immune system. However, no one had previously taken the time to verify if this protein was involved in the regulation of metabolism. This is precisely what this team of Canadian and American researchers did, thanks to a series of mutant or genetically modified mice producing little or no SHP-1.

"Our results indicate that these mice are extremely sensitive to insulin and, consequently, they are very effective in metabolising glucose at the level of the liver and the muscles," notes André Marette. In addition, the researchers highlighted that SHP-1 inhibits the decomposition of insulin by the liver. "This could explain the increase in the insulin concentrations of certain metabolic disorders associated with obesity," indicates the researcher.

"The results of Andre Marette and his team represent an important step in the development of a new therapeutic approach in the fight against diabetes. Advances in the treatment of diabetes are needed to improve the lives of the more than two million Canadians already affected by it and the many more who will develop the disease in the years to come. The study is a perfect example of the potential benefits of investing in health research," says Dr. Diane Finegood, based in Vancouver and Scientific Director of the CIHR Institute of Nutrition, Metabolism and Diabetes.

"By inhibiting the activity of SHP-1, it would perhaps be possible to restore better control of blood glucose," suggests professor Marette. The difficulty, however, is to reach that point without blocking the essential part played by this protein in the immune system. The SHP-1 protein is present in humans, but its role in the regulation of the metabolism of glucose and in the development of type 2 diabetes remains to be shown.

"Good glucose control is essential for managing diabetes and preventing the debilitating complications associated with diabetes," says Dr. Paula Dworatzek, Senior Research Associate, Canadian Diabetes Association. "We congratulate Dr. Marette and his team for these initial findings, which will pave the way for his team and others to pursue a potential new therapy in the management of diabetes."

Posted by dlife at 08:51 AM | Comments (0)

New Pathways for Autoimmune Treatment Identified

May 28, 2006 (Eurekalert) - A rare genetic defect that can trigger a host of diseases from type 1 diabetes to alopecia has helped explain the imbalance of immune regulator and killer cells in autoimmune disease.

Mutation in the Aire gene causes APS1, a disease causing two out of three problems – an underactive parathyroid, yeast infection of the skin and/or mucous membrane and adrenal gland insufficiency – by age 5 and up to 16 autoimmune diseases over a lifetime.

The same mutation caus es a defect in iNKT cells, a type of regulatory cell that helps the immune system fight infections while suppressing errant T cells bent on attacking the body, Medical College of Georgia researchers say.

This finding opens new pathways for treating or preventing APS1, or autoimmune polyglandular syndrome type 1, and potentially other autoimmune diseases as well, researchers report in the June issue of Nature Medicine.

"The body should maintain a balance between killing and suppression," says Dr. Qing-Sheng Mi, immunologist and lead and co-senior author. "If you are killing too hard, it can induce autoimmune disease. If you regulate suppression too hard, you can get cancer. iNKT cells help maintain a healthy balance. But patients with autoimmune disease may not have enough functional iNKT cells."

"Aire controls the development and function of iNKT cells," says Drs. Jin-Xiong She, director of the MCG Center for Biotechnology and Genomic Medicine and co-senior author. "This relationship means that iNKT cells are critical to most autoimmune diseases and manipulating the iNKT cell population is one possible way to cure autoimmune disease."

A lipid purified from sea plants, called alpha-GalCer, is already under study as a way to boost iNKT cell numbers and fight autoimmune disease as well as cancer. iNKT cells' reactivity to alpha-GalCer, prompted the scientists to use it as a marker to examine the status of these cells in a mouse missing the Aire gene. That Aire knockout is a good model for humans with APS1.

They found significantly fewer iNKT cells in the thymus, spleen, liver and bone marrow and severely impaired maturation of those cells in mice missing the Aire gene. And the mice given alpha-GalCer had significantly reduced autoantibody production.

In 2001, Dr. Terry L. Delovitch and his colleagues at Canada's Robarts Research Institute, including Dr. Mi, reported in Nature Medicine that using alpha-GalCer to boost iNKT cells and re-establish a healthy balance of good and bad immune cells prevented development of type 1 diabetes in an animal model for the disease.

But Drs. Mi and She say new iNKT boosters likely are needed because the action of alpha-GalCer somehow depends on individual genetic architecture as well as other factors. Under certain conditions, the drug can help or worsen an autoimmune disease by producing good or bad cytokines. That's why it also has worked for some cancers and why a modified version of the glycolipid or totally different drugs may work better, Dr. She says. "By understanding more, we are better able to come up with better targets," he says.

"iNKT development is still the big question," says Dr. Mi. "Not only how they develop, but how they develop properly."

The researchers watched the key regulatory cells come out of the bone marrow and go to the thymus where all T cells go for a process of positive and negative selection and maturation. Positive selection eliminates cells that are dysfunctional. Negative selection is eliminating T-cells that recognize the body's own proteins, Dr. She says.

Other researchers recently confirmed that the Aire gene is involved in negative selection by controlling some protein expression in the thymus, Dr. Mi says. The thymus is supposed to express most body proteins so any T cells that would react to them can be eliminated through negative selection, he says. "But Aire's role in protein expression is not sufficient to explain all the clinical symptoms of patients with APS1," Dr. Mi says. "The Aire gene must have other immune functions."

iNKT cells also go through a development process but via a somewhat different path than that of other T cells. MCG researchers have learned medullary epithelial cells in the thymus are critical to proper iNKT cell development. A defective Aire gene disrupts this natural nurturing relationship by disrupting medullary epithelial cell function, leading to insufficient numbers of iNKT cells.

"Whether or not you develop autoimmune disease to a large degree depends on the balance of these bad T cells that recognize the body's own protein and regulatory T cells," Dr. She says. "It's all about balance."

Dr. Mi received a Junior Faculty Travel Award from the American Association of Immunologists for the iNKT research during the association's annual meeting in May.

Posted by dlife at 08:54 AM | Comments (0)

Topical Hedgehog Agonist Accelerates Wound Healing in Diabetes

Curis, Inc. (NASDAQ: CRIS), a therapeutic drug development company, today announced the publication of preclinical data in the journal Circulation, showing that topical Sonic Hedgehog gene therapy accelerated wound healing in an animal model of diabetes. This beneficial effect appeared to involve the enhanced mobilization of blood vessel-forming progenitor cells from the bone marrow to the wound site, whose presence was interpreted as helping to explain the increased blood supply observed within the healing wound. The paper, "Topical sonic hedgehog gene therapy accelerates wound healing in diabetes by enhancing endothelial progenitor cell-mediated microvascular remodeling", was authored by Douglas W. Losordo and others from St. Elizabeth's Medical Center in Boston as part of a collaboration with Curis. This publication expands on the data presented May 2005 at the 66th Annual Meeting of the Society for Investigative Dermatology.

"This paper provides a proof-of-concept demonstration that therapeutic activation of the Hedgehog pathway could potentially be used to treat wounds in people suffering from diabetes, which is a large and growing market where current treatments are inadequate," said Daniel R. Passeri, President and Chief Executive Officer.

About the Hedgehog Agonist Program

The Hedgehog agonist program was exclusively licensed to Wyeth Pharmaceuticals in February 2004. Under the terms of the license agreement, Curis retained the right to develop Hedgehog agonists for topical treatment to stimulate hair growth. The license agreement was subsequently amended to broaden Curis' development rights to include topical applications to treat or prevent skin diseases or disorders. In both instances, Wyeth must approve any compound that Curis will develop under its retained development rights. In December 2004, Wyeth approved a group of Hedgehog agonist compounds for use in Curis' retained programs. Curis licensed the Hedgehog agonist technology to Procter & Gamble for the development and commercialization of topical dermatological and hair growth products. This new report suggests that the Hedgehog agonists may be useful for development in a wound healing program. Curis retained rights to this indication for veterinary use and Procter & Gamble has rights to use the Hedgehog agonists for wound healing under its topical dermatological rights.

Posted by dlife at 02:57 PM | Comments (0)

Poor Adolescents More Likely to be Overweight Today than 30 Years Ago

Newswise 05/24/06 — The percentage of adolescents aged 15-17 who are overweight today is about 50 percent higher in families below the poverty line in comparison to those at or above it. That difference was not present in the 1970s and 1980s, according to researchers from the Johns Hopkins Bloomberg School of Public Health and other institutions

The scientists based their analyses on U.S. national health surveys spanning 33 years. Adolescents aged 15-17 who were in families with an income below the poverty line were more likely to have higher caloric intake from sweetened beverages, to be physically inactive and to skip breakfast. Each of these factors may have played a role in the growing difference in the percentage of overweight teens associated with family poverty. This trend was specific to adolescents aged 15-17 and was not found among adolescents aged 12-14. The study is published in the May 24/31, 2006, issue of the Journal of the American Medical Association (JAMA).

The prevalence of overweight adolescents in the United States has more than doubled in the past three decades. And the percentage of adolescents who are overweight has increased significantly faster among the poor in comparison to the non-poor over the past decade,” said Richard A. Miech, PhD, MPH, lead author of the study and an associate professor in the Johns Hopkins Bloomberg School of Public Health’s Department of Mental Health.

The study authors analyzed four U.S. National Health and Nutrition Examination Surveys (NHANES)—1971-1974, 1976-1980, 1988-1994, 1999-2004. Children with a body mass index at or above the 95th percentile for their age and sex in the 2000 Centers for Disease Control and Prevention growth charts were classified as overweight. The authors found that 15- to 17-year-old adolescents with higher daily intake of calories from sweetened beverages were significantly more likely to be overweight. In addition, among high school adolescents, the percentage of daily calories from drinking sweetened beverages has increased by more than 20 percent over the past decade (from 10.7 percent to 13.2 percent). Sweetened beverage consumption also increased at a faster rate among poor versus non-poor adolescents (67 percent versus 14 percent). Today, high school adolescents who live below the poverty line are more likely to be physically inactive and also more likely to skip breakfast, both of which are associated with excessive weight gain. The researchers did not see this same trend in adolescents aged 12-14. However, non-poor black adolescents in this age range were more likely to be overweight than their poor counterparts.

The researchers note that as more and more adolescents gain excessive weight, the associated consequences—type 2 diabetes, hypertension, sleep apnea, poor quality of life and morbidity in adulthood—will also increase.

“I believe that the trend in poverty and adolescent obesity can be reversed, if there is sustained public will to do so. While there is no silver bullet that will end this trend or the obesity epidemic in general, we know many of the major factors involved and we are beginning to do something about them,” said Miech. “The recent, voluntary withdrawal of soft drinks from schools is a good step. We need to further develop and implement additional programs to improve adolescent nutrition and physical exercise, especially among the poor.”

NOTE: Unlike definitions for adults, the Centers for Disease Control and Prevention uses “overweight” to refer to the highest body mass index for children and adolescents. Therefore, it is inaccurate to use the term “obese” when referring to elevated body mass index in this age group.

Posted by dlife at 02:47 PM | Comments (0)

New Gene Therapy Technique for Potential Treatment of Type I Diabetes

Newswise (May 22, 2006) — Researchers at Baylor University Medical Center at Dallas and the Baylor Research Institute have developed a novel technique to deliver insulin genes to the pancreas, the organ that produces the body’s insulin. This approach is a major step in the potential treatment of Type I diabetes since patients with the disease do not produce enough insulin on their own. The research results were published in the May 2006 issue of the Proceedings of the National Academy of Sciences.

Insulin is a hormone that allows blood glucose (blood sugar) to enter the cells of the body to be used for energy. The technique, known as ultrasound-targeted microbubble destruction (UTMD), delivers these insulin genes to the organ via microscopic “bubbles.” Once the bubbles reach their target, they are burst with ultrasound releasing the insulin genes into the pancreas.

Using UTMD, researchers delivered the bubbles containing human insulin genes into the pancreas of rats and later found that the rat’s blood sugar had been subsequently lowered. Another gene that regulates insulin production, known as hexokinase I, was successfully delivered using UTMD as well, and resulted in increased blood insulin and decreased blood sugar in the rats.

“Not only was their blood sugar lowered, but there was no evidence of any damage to the pancreas,” says Paul Grayburn, M.D., principal investigator of the study. “Other forms of gene therapy are usually invasive and unlike the UTMD technique, do not target the tissues and organs specifically.”

Currently, patients with Type I (juvenile onset) diabetes must inject themselves with insulin daily to keep their blood sugar levels balanced in addition to following strict nutritional guidelines. Dr. Grayburn says that the UTMD technique is one of the most important steps in the development of a successful treatment of diabetes without the need for daily insulin injections.

“Now that we have successfully delivered insulin genes to the pancreas, our ultimate goal is to research the regeneration of insulin-producing cells in patients with Type I diabetes,” says Dr. Grayburn.

In the future, Dr. Grayburn says that the UTMD technique for gene delivery can be used to deliver therapeutic agents to other organs as well.

Nationwide, more than one million people have Type 1 (juvenile onset) diabetes. Diabetes – the fifth deadliest disease in the United States – affects the body’s ability to produce or respond to insulin. People with Type 1 diabetes are at increased risk for many serious complications, including heart disease, blindness, nerve damage and kidney damage.

Dr. Grayburn’s research was supported by a grant from the National Institutes of Health and by the Mary Alice M. and Mark Shepherd, Jr. Endowment Fund in Cardiology and Cardiovascular Surgery and Research. The study was also held in conjunction with researchers from Duke University and UT Southwestern Medical Center.

Baylor University Medical Center at Dallas, a 997-bed not-for-profit academic hospital, is a major patient care and research center in the southwest. In 2005, U.S. News & World Report recognized Baylor Dallas for the 13th consecutive year in its “America’s Best Hospitals” guide in several medical specialties. Baylor Dallas serves as the flagship hospital of Baylor Health Care System.

The Baylor Research Institute, an affiliate of Baylor Health Care System, promotes and supports clinically relevant research, bringing innovative treatments from the laboratory workbench to the patient bedside. Investigators at Baylor are conducting more than 500 active research protocols spanning more than 20 medical specialties.

Posted by dlife at 03:13 PM | Comments (0)

Baylor Researchers Develop 'Bubble' Technique for Potential Treatment of Type I Diabetes

DALLAS (May 22, 2006) — Researchers at Baylor University Medical Center at Dallas and the Baylor Research Institute have developed a novel technique to deliver insulin genes to the pancreas, the organ that produces the body's insulin. This approach is a major step in the potential treatment of Type I diabetes since patients with the disease do not produce enough insulin on their own. The research results were published in the May 2006 issue of the Proceedings of the National Academy of Sciences.

Insulin is a hormone that allows blood glucose (blood sugar) to enter the cells of the body to be used for energy. The technique, known as ultrasound-targeted microbubble destruction (UTMD), delivers these insulin genes to the organ via microscopic "bubbles." Once the bubbles reach their target, they are burst with ultrasound releasing the insulin genes into the pancreas.

Using UTMD, researchers delivered the bubbles containing human insulin genes into the pancreas of rats and later found that the rat's blood sugar had been subsequently lowered. Another gene that regulates insulin production, known as hexokinase I, was successfully delivered using UTMD as well, and resulted in increased blood insulin and decreased blood sugar in the rats.

"Not only was their blood sugar lowered, but there was no evidence of any damage to the pancreas," says Paul Grayburn, M.D., principal investigator of the study. "Other forms of gene therapy are usually invasive and unlike the UTMD technique, do not target the tissues and organs specifically."

Currently, patients with Type I (juvenile onset) diabetes must inject themselves with insulin daily to keep their blood sugar levels balanced in addition to following strict nutritional guidelines. Dr. Grayburn says that the UTMD technique is one of the most important steps in the development of a successful treatment of diabetes without the need for daily insulin injections.

"Now that we have successfully delivered insulin genes to the pancreas, our ultimate goal is to research the regeneration of insulin-producing cells in patients with diabetes," says Dr. Grayburn.

In the future, Dr. Grayburn says that the UTMD technique for gene delivery can be used to deliver therapeutic agents to other organs as well.

Nationwide, more than one million people have Type 1 (juvenile onset) diabetes. Diabetes – the fifth deadliest disease in the United States – affects the body's ability to produce or respond to insulin. People with Type I diabetes are at increased risk for many serious complications, including heart disease, blindness, nerve damage and kidney damage.

Posted by dlife at 08:39 AM | Comments (0)

Joslin Diabetes Center-Led Study Shows Different Insulin Signaling Components Control Glucose and Lipid Metabolism in the Liver

New Findings May One Day Advance Treatments to Prevent Type 2 Diabetes and Metabolic Syndrome

BOSTON, May 12, 2006 (Joslin) - Insulin uses two distinct mechanisms to control glucose and the metabolism of blood fats (lipids) in the liver, a new Joslin Diabetes Center-led study has discovered. Failures in each of these networks can lead to serious health problems: the breakdown of glucose metabolism that can lead to type 2 diabetes, and the malfunction of lipid metabolism contributing to metabolic syndrome, which is a cluster of conditions that puts people at increased risk of heart disease, vascular disease and type 2 diabetes.

The new study, led by C. Ronald Kahn, M.D., and Cullen Taniguchi, M.D., Ph.D., of Joslin Diabetes Center in Boston and their colleagues, is published in the May edition of Cell Metabolism. The findings open the door to the development of new treatments that one day may target directly the conditions that contribute to type 2 diabetes and the metabolic syndrome.

"Patients with the metabolic syndrome have high levels of both glucose and lipids in the blood. We now understand that insulin that controls the pathways that control glucose levels are different from those that regulate lipid levels. By targeting these specific pathways, we might be able to improve problems with glucose metabolism, lipid metabolism or both," says Dr. Kahn, President of Joslin Diabetes Center and Mary K. Iacocca Professor of Medicine at Harvard Medical School.

Diabetes affects an estimated 20.8 million children and adults in the United States -- 7 percent of the population. An estimated 14.6 million Americans have been diagnosed, leaving 6.2 million Americans unaware that they have the disease. In addition, 41 million Americans are thought to have pre-diabetes, or elevated blood glucose levels that put them at risk for developing type 2 diabetes. If untreated or poorly treated, diabetes can lead to blindness, kidney disease, stroke, nerve damage and circulation problems that can result in limb amputations.

Patients generally are diagnosed with metabolic syndrome if they have three or more of the following conditions: abdominal obesity; high cholesterol levels or triglycerides; low levels of good cholesterol; high blood pressure; and high blood glucose. The metabolic syndrome has become increasingly common in the United States, and according to a recent survey, is seen in 24 percent of all adult Americans above age 20 and in about 40 percent of those above age 60.

Exploring the role of the liver

The liver is the body's primary chemical factory, and among its key roles is keeping glucose levels in the blood constant between meals. The liver also produces and packages cholesterol and triglycerides to send throughout the body. Insulin's activity in the liver controls both of these processes, but, until now, researchers have not understood how insulin does its job.

"In one of its roles, insulin tells the liver that you have just eaten, that it can stop producing glucose since the food you have just eaten will, for a while, supply an adequate amount," says Dr. Taniguchi, a postdoctoral fellow in Joslin's Section on Cellular and Molecular Physiology and lead author of the paper. "Insulin also is the trigger that tells the liver how to handle lipids. We have been trying for many years to understand how insulin provides these signals, and now we have shown that insulin controls each process differently."

Insulin drives the liver's metabolic functions by activating a molecule called phosphoinositide 3-kinase (PI3K), which then recruits other enzymes to carry out its orders. While researchers knew that the PI3K pathway was important to insulin's action, until now they didn't know how insulin uses PI3K to control either glucose or lipid metabolism.

Using mice bred to lack specific subunits of the PI3K pathway, the researchers discovered that mice that could not activate the protein kinase Akt had increased glucose production in the liver, impaired glucose tolerance and increased levels of insulin in the blood, all contributors to type 2 diabetes. On the other hand, those mice with defects in the atypical forms of the enzyme protein kinase C (PKC) had decreased lipids in the blood and reduced levels of a protein called SREBP, which is critical for regulating fatty acid and cholesterol in the blood. (This particular form of the PKC enzyme is distinct from the form known as PKC-beta, which is activated by high blood glucose and is linked to many diabetic complications, including those of the eye and the blood vessels.)

"People used to think that Akt controlled both glucose and the lipids in the liver," says Dr. Taniguchi. "Now we know that Akt has nothing to do with the lipids. Akt controls the glucose part and the atypical PKC controls the lipids part." He explains that some patients with fatty liver disease don't have any glucose problems, while others with type 2 diabetes don't have problems with their lipids. "Now that we have uncovered the important molecules for each condition," says Dr. Taniguchi, "we can begin to look for ways to specifically target just the lipids or just the glucose."

Others participating in the study included: former Joslin fellow Tatsuya Kondo, M.D., Ph.D., of the Graduate School of Medical Science, Kumamoto University, Japan; Mini Sajan, Ph.D., and Robert Farese, Ph.D., of the University of South Florida College of Medicine; Ji Luo, Ph.D. and Lewis C. Cantley, Ph.D., of Beth Israel Deaconess Medical Center, Boston, and Harvard Medical School (HMS); Roderick Bronson, D.V.M., of HMS; and Tomoichiro Asano, M.D., of the University of Tokyo.

Posted by dlife at 08:56 AM | Comments (0)

University of Mississippi Medical Center Takes Diabetes Care From Bad to Best

JACKSON, Miss., May 11 (AScribe Newswire) - Mississippi has traditionally been the worst state in the nation for patients with diabetes. The incidence of diabetes is higher here, the complications more numerous, and until now, the quality of care was at rock bottom. The complications from diabetes - kidney failure, amputation, blindness and heart disease - are both life-threatening and severely debilitating.

A new system of diabetes care, however, is changing all that. In several clinics around the state (three in the Mississippi Delta where diabetes numbers soar) patients have reduced their risk for complications by 70 percent in just six visits.

The scourge of the state has met its enemy - Dr. Marshall Bouldin, associate professor of medicine at the University of Mississippi Medical Center, where he started the first clinic in 1999. The growth of the system wasn't unplanned. Dr. Dan Jones, vice chancellor for health affairs at the Medical Center, urged Bouldin to create a system that could be replicated in other parts of the state to bring diabetes care up to the national standard and help prevent some of the tragic complications of the disease.

Now, with six years of data and experience in several locations, Bouldin has shown that patients in the clinics, even those who were formerly considered "difficult," average a two-point drop in their long-term levels of blood sugar, and for every point that level decreases, the patient reduces his or her risk for complications by 35 percent. Even more encouraging, there is no disparity of outcomes between African-Americans and Caucasians.

Bouldin said that the prevalence of diabetes among adults in Mississippi increased from 7.3 percent to 11 percent from 1999-2001. In some subsets of the Mississippi population, the prevalence is even higher. Among African-American women between 55-64, for example, 34.7 percent have diabetes. And diabetes definitely hits hardest among the poor. Mississippi is the poorest state in the nation, and counties that make up the Mississippi Delta are the poorest of the poor. Still, in this population, Bouldin's system has produced outcomes equal to or better than those in affluent white communities in the Northeast.

"Diabetes control ultimately hinges on the patient's ability to manage his or her own diabetes, and everyone responds to interventions that allow them to do that," Bouldin said.

Pete Johnson, the federal co-chairman for the Delta Regional Authority, said his group was looking for models of health care delivery when it became obvious that health was a key driver of the economy. "You cannot turn an economy around if you don't have a competitive work force, and you can't have a competitive work force if they're not healthy." The authority, created by Congressional act in 2000 under the administration of President Bill Clinton, works to improve conditions in 240 counties and parishes in eight states.

"We're right at the beginning of taking this region-wide," Johnson said. "We were looking for an efficient model of health care delivery, and it was right under our noses."

Johnson, it turns out, is friends with Bouldin's father, the famous portrait artist from Clarksdale. "He sits two rows in front of me in church, and one Sunday, when Marshall was home for the weekend, he told me about his project and how he thought it could work in the Delta. We looked at his data and analyzed his results and decided it was a program we should embrace and replicate."

Funding for the Delta clinics comes from the Delta Health Alliance, under the direction of Dr. Cass Pennington. One thing that appeals to both agencies is the cost-effectiveness of the clinics. "It costs about $250,000 to start up a clinic, but reimbursement from Medicaid and Medicare make it self-sustaining," Johnson said.

Pennington said his agency is impressed with the strong patient education component of the diabetes project and the impact it has had on the health of the Delta. "Employers in the Delta cite frequent employee absences because of sickness as a major problem. And they identify diabetes as the major cause of those absences. This program is a Godsend, and it will have a tremendous impact on the Delta counties."

Pennington also credited Bouldin for his perseverance in seeing the clinics implemented. "I think his car could find its way to the Delta without a driver."

But Bouldin knows that he can't be in all locations all the times he's needed, so he's developed another collaboration with the University of Tennessee to use its telemedicine capabilities. "This way, I can meet with the staff of the clinics in the Delta once a week and go over patient records with them or discuss any problems they may have encountered."

Bouldin also trains local physicians to use the system he's devised for diabetes care, so it can be done in his absence. But the system uses physicians very sparingly, and that's one of the reasons it can be replicated in regions where physicians are scarce.

"We don't do anything that's revolutionary. We use all the tried-and-true methods of diabetes management."

What is perhaps revolutionary is the absence of the traditional hierarchy of care starting with the physician at the top and the patient educators and dieticians at the bottom. "In this model, every professional role is critical," Bouldin said. Nurse practitioners, RNs, diabetic educators, pharmacists and dietitians all work as a team to teach and care for patients. Nurse practitioners and pharmacists manage diabetes care much as a physician specialist would. Bouldin, the physician, manages medical problems beyond the scope of the other professionals and supervises quality assurance.

"As far as we know, this is the first time pharmacists have ever been used in this specific role of diabetes management," he said, "and our studies have shown that they're particularly effective in reducing blood sugar levels."

The risk for complications, Bouldin explained, correlates with the concentration of sugar in the blood. The insulin in individuals who don't have diabetes allows glucose (sugar) to enter cells and be converted to energy, to synthesize proteins and store fat. In patients with diabetes, sugar and fat stay in the bloodstream and damage vessels and nerves that can eventually lead to kidney disease, blindness, amputation and heart disease.

No system in Mississippi (and few in the country) has reported outcomes as good as Bouldin's, and especially not in the high-risk populations the clinics serve.

"Our outcomes have been consistent over six years, and we were surprised that results could be seen so quickly. Our patients average a two-point drop in their blood sugar levels in just six months," he said.

The clinical outcomes of Bouldin's system have not escaped notice on a national level. In the last three years, Bouldin has succeeded in obtaining $3.5 million in external funding with more funding anticipated. In May 2005, Bouldin presented results from the various clinics to the Bipartisan Committee on Health Information Technology on Capitol Hill and made a special presentation to Medicare staff in Baltimore, Md., at the request of the Medicare director.

"I think the general feeling is that if we can do this in Mississippi, it can work anywhere," Bouldin said.

To Bouldin, one of the key components of success is the degree of collaboration between agencies, institutions, the local community and the federal government. In addition to the Delta Regional Authority, the Delta Health Alliance and the University of Tennessee, other active partners are the Joslin Diabetes Center, Mississippi Valley State University, Delta State University, Mississippi State University, and the Centers for Disease Control (CDC).

The CDC will put a field station in the Delta to work with the Delta Health Alliance and the diabetes project. "We had always planned that the diabetes program we first established at the Medical Center in 1999 would really be a test case for the management of chronic disease. If you've done diabetes well, you have essentially already done high blood pressure, dyslipidemia and cardiovascular mortality. The partnership with CDC will enable the coalition to develop regional programs along these lines."

Posted by dlife at 08:58 AM | Comments (1)

Ghrelin: A Player in Diabetes But Not Obesity?

HOUSTON, May 10, 2006, (EurekAlert) - Ghrelin, a hormone long considered a key player in obesity, may instead take a major role in maintaining the balance between insulin and glucose and the development of diabetes, said Baylor College of Medicine researchers in a report in the current issue of the journal Cell Metabolism.

"Everybody has been pushing the connection between obesity and ghrelin," said Dr. Roy G. Smith, director of the BCM Huffington Center on Aging, "Companies have been developing ghrelin antagonists as anti-obesity drugs. Now these drugs may have a value in treating diabetes."

The downside is that the drugs may not forestall obesity.

In studies in his laboratory, mice bred to be deficient in both ghrelin (which stimulates appetite) and leptin (associated with controlling obesity) could be expected to be thin or of normal body weight, said Smith, also a professor of Molecular and Cellular Biology at BCM. That was a surprise, said the paper's first author, Dr. Yuxiang Sun, a BCM instructor in the center.

"They were just as fat as the mice bred to lack only leptin," said Smith.

However, their glucose levels were lower than in leptin-deficient mice. When Sun did a glucose tolerance test on the mice, she found much lower levels in the animals that did not produce either ghrelin or leptin.

"They were more resistant to glucose because they secreted more insulin in response to the glucose challenge," said Smith.

When Sun and Smith investigated further, they found lower levels of uncoupling protein-2 (Ucp2) in cells called pancreatic islets (where insulin is made). Reducing Ucp2 improves the cell's ability to make ATP, the cell's energy molecule, thereby increasing the sensitivity of the pancreatic beta cell (the cell in the pancreas which produces insulin) to glucose-induced insulin release. Further tests in animals lacking ghrelin, showed that besides increased insulin secretion, their sensitivity to insulin was increased, said Sun. "That means glucose was cleared more efficiently."

While Smith sees a role for drugs that block ghrelin in treatment of type 2 diabetes (which usually occurs in adulthood and is often associated with obesity), he sounds a cautionary note.

"If through this process, you increase ATP production by the beta cell, you may in the long-term get oxidative stress which could eventually destroy the beta cell," he said. He said he does not yet have data to determine whether that is true or not.

In an accompanying analysis, Dr. Rexford S. Ahima of the University of Pennsylvania School of Medicine, wrote, "Overall, the studies provide compelling evidence that ghrelin has unique dual effects on glucose homeostasis (the balance between glucose and insulin), at least in a genetic model. Ghrelin antagonism (or blocking) may be a new approach for treating type 2 diabetes by improving insulin secretion in response to glucose and enhancing peripheral insulin action. The challenge is to ascertain if these results in rodents can be translated to patients."

Others who participated in the research include Drs. Mark Asnicar, Pradip K. Saha and Lawrence Chan, all of BCM.

Posted by dlife at 09:01 AM | Comments (0)

Antidepressant Drug May Prevent Recurrence of Depression in Patients with Diabetes

Managing depression helps control blood glucose levels

May 8, 2006 (EurekAlert) - A team of researchers at Washington University School of Medicine in St. Louis found that an antidepressant medication may reduce the risk of recurrent depression and increase the length of time between depressive episodes in patients with diabetes.

"That's important not only because people with diabetes will feel better if we can control their depression. It's also key to helping manage blood sugar," says Patrick J. Lustman, Ph.D., principal investigator and professor of psychiatry. "As depression improves, glucose levels also tend to improve."

Although depression affects about 5 percent of the general population, the rate is about 25 percent for patients with diabetes. Lustman's team previously demonstrated that treatment with antidepressant drugs and psychotherapy is an effective way to treat depression in patients with diabetes, but often depression would quickly redevelop.

"As we better understand depression, it's clear that for many patients, it is a chronic and recurring disease," Lustman says. "That appears to be especially true for patients with diabetes compared to those otherwise free of medical illness"

Although they knew that short-term treatment with antidepressants was helpful with mood and with control of blood glucose, Lustman's team didn't know whether the drug could prevent the recurrence of depression in patients with diabetes. He also didn't know what would happen to glucose levels in the months following successful depression therapy.

So Lustman teamed up with investigators at the University of Arizona, Tucson, and at the University of Washington, Seattle. They studied a total of 152 patients with diabetes at the three sites. The sample included patients with type 2 diabetes and patients with juvenile, or type 1, diabetes. Study participants averaged just over 50 years of age, and all had recovered from an episode of depression following treatment with sertraline (Zoloft®).

After their depression was under control, half of the study patients continued to take sertraline while the other half took an inactive placebo. Patients were followed for up to a year or until their depression recurred. During that time, investigators regularly measured blood glucose levels by keeping track of hemoglobin A1C, which reflects an individual's control of blood glucose over two to three months.

At one year, more than 65 percent of those still taking sertraline remained in remission from their depression. Only about 48 percent of those taking placebo were still in remission. On average, those who continued to take sertraline stayed free of depression four times longer than those who did not continue to take medication. Blood glucose levels remained lower in both groups of patients, as long as depression remained under control.

"That's very important," Lustman says. "We now know that controlling depression, by whatever method -- whether with exercise, activity, cognitive therapy or medication -- improves the likelihood that blood glucose will be better controlled. That's the key to preventing the complications of diabetes, such as eye disease, neuropathy and kidney disease."

Posted by dlife at 09:10 AM | Comments (0)

Diabetes Research at UH 'Crystalizes' With Major Finding

New insulin-production method holds promise for diabetics, impacts other fields

HOUSTON, May 8, 2006 (EurekAlert) – A University of Houston professor and his student have made a major discovery in the field of diabetes research and diagnosis, finding a new mechanism for the formation of insulin crystals in the pancreas.

Peter Vekilov, associate professor of chemical engineering, and Dimitra Georgiou, a recent doctoral graduate in chemical engineering, both in UH's Cullen College of Engineering, are behind this breakthrough. Since insufficient insulin production in the pancreas is one of the primary causes of adult-onset diabetes, Vekilov and Georgiou are studying the process of how insulin is produced in the first place. Understanding how the body creates this hormone will make it easier for researchers to discover why some individuals do not produce enough insulin and thus develop diabetes, Vekilov said. Specifically, the two have focused on the creation of insulin crystals, the form in which insulin is stored in the pancreas before it is released in the bloodstream.

"It is possible that the insulin deficiency happens when the crystals don't form properly and then part of the insulin that is produced gets destroyed," Vekilov said.

Proinsulin, a molecular precursor to insulin itself, is the reason for these crystals. After an insulin molecule is produced from proinsulin, it attaches to an insulin crystal only in special locations where other insulin molecules have formed right angles, called kinks. Using atomic-force microscopy, they discovered a new mechanism by which insulin molecules attach themselves to crystals to form these kinks. They found that groups of insulin blocks create large protrusions, dubbed "mounds" by Vekilov and Georgiou. The very nature of these mounds results in the creation of multiple kinks – far more, in fact, than other methods of kink formation.

By providing so many spaces where insulin molecules can attach to an insulin crystal, these mounds allow for the rapid growth of that crystal and only form when there is a surplus of insulin that allows for rapid crystal growth. Since no mounds appear when there is a lack of insulin and insulin crystals both grow and dissolve at kinks, mounds are important sources of a crystal's net growth.

"Typically in nature, fast growth also results in fast dissolution," Vekilov said. "But this process cheats physics because when there isn't a lot of insulin, mounds don't form. It's an asymmetric mechanism that has no balance."

While this discovery will play a significant role in gaining a better understanding of diabetes, it also is an historic find in the area of crystal formation and use, as only the third mechanism of crystal formation ever discovered. Before this finding, there were only two known ways that crystals grew – the first was proposed in 1876 and the second in 1968. Though the first and second discoveries, proposed by prominent American scientist and founder of modern thermodynamics J.W. Gibbs and by Russian scientist V.V. Voronkov, respectively, only recently demonstrated their applicability to real systems, this latest mechanism has already been experimentally proven in the work by Vekilov and Georgiou.

"It is possible that crystals composed of materials other than insulin also grow in this manner," Vekilov said. "If so, this discovery could significantly impact any number of fields that deal with crystals. It can help us understand all processes of crystal formation, including semiconductor and optical materials, geological crystallization, ice formation and the physiological and pathological crystallization of proteins and small molecules."

Posted by dlife at 09:05 AM | Comments (0)

Scientists Find Gene in Obese Mice That Increases Type 2 Diabetes

MADISON, May 7, 2006 (EurekAlert) - In a painstaking set of experiments in overweight mice, scientists from the University of Wisconsin-Madison have discovered a gene that appears to play an important role in the onset of type 2 diabetes.

The finding is important because it provides evidence that the same gene in humans could provide clinicians with a powerful tool to determine the likelihood that some individuals will acquire the condition. Moreover, the finding that the gene works through a pathway not generally studied in the context of diabetes, suggests new avenues to explore in the search for new drugs to treat or prevent the disease, says Alan Attie, a UW-Madison professor of biochemistry and the senior author of the study published this week (May 7) in the journal Nature Genetics.

Type 2 diabetes is the most common form of the condition in the United States, with an estimated 16 million Americans afflicted with the disease. It is caused by an inability of the pancreas to produce enough insulin, or by the body's reduced ability to respond to insulin, or both. Insulin is necessary for the body to properly utilize sugar.

Often, the development of type 2 diabetes is caused by obesity. Obese individuals tend to have insulin resistance; that is, it takes more insulin for the body to respond normally. Type 2 diabetes occurs when the pancreas is unable to manufacture enough insulin to compensate for the body's increased demand for the hormone, which it does by growing more insulin-producing beta cells or by ramping up insulin secretion.

The Wisconsin study, comparing two strains of obese mice differing in susceptibility to diabetes, helps explain why this is so.

"Most people who are obese don't have diabetes, but people who are obese are insulin resistant," says Attie. "If there is a fall-off in insulin production, that's when you go from prediabetes to diabetes."

The gene found by Attie's group likely influences the ability of the pancreas to recruit a type of cell essential for constructing the walls of blood vessels. The beta cells of the pancreas, which are the critical insulin producing cells of the organ, are found clustered together in structures called islets and are nourished by a complex network of small blood vessels. If there are changes in this gene, the Wisconsin scientists believe, the blood vessels within islets may not form properly.

The consequences of this, says Attie, may be that not all beta cells receive the proper nutrition critical for their survival, that they may not receive the proper signals to secrete insulin, or that the blood vessels are insufficient to receive all the insulin they secrete.

The findings, says Attie, provide new insight into a process that might be impaired in individuals who fail to increase or maintain beta cell mass in the pancreas and sufficient insulin secretion to compensate for resistance. What's more, because the Wisconsin group believes the gene plays a role in regulating the tiny blood vessels that nourish the insulin-producing islet cells of the pancreas, it implicates features beyond defective beta cells in the onset of the disease.

"The hope is this will open up scientists' thinking to realize that there are other cells of importance (in diabetes) beyond beta cells," says Susanne Clee, the lead author of the new Nature Genetics study.

Genetic factors are believed to account for roughly half of an individual's risk of developing type 2 diabetes. Knowing which genes might contribute to the onset of the disease can help clinicians develop profiles of obese individuals at the greatest risk. Importantly, the new Wisconsin study looks beyond genetic influences exerted directly on insulin resistance and secretion to genes that govern structures of the pancreas that may help the organ compensate for diminished insulin production and insulin resistance. In humans, the search for such genes has yielded little success so far.

The new findings, according to Attie, will give scientists searching for those genes in people a roadmap to help locate a new "genetic bottleneck" that contributes to the onset of type 2 diabetes in humans.

"We hope this is replicating what happens in humans," Attie says. "Our work covered a lot of genetic real estate, and it should help others drill down to something similar in people. Time will tell, but I think we'll have answers to the question about how general this is pretty quickly."

In addition to Attie and Clee, authors of the new study include Brian S. Yandell, Kathryn M. Schueler, Mary E. Rabaglia, Oliver C. Richards, Summer M. Raines, Edward A. Kabara, Daniel M. Klass, Eric T.-K. Mui, Donald S. Stapleton, Mark P. Gray-Keller, Matthew B. Young, Jonathan P. Stoehr, Hong Lan, Igor Boronenkov, Phillip W. Raess, and Matthew T. Flowers.

Posted by dlife at 09:03 AM | Comments (0)

Patients Improved Diabetes Control Over 5-Year Period, But Many Fail to Achieve Treatment Goal

Quest Diagnostics Health Trends(TM) Diabetes Report Is Based on 14.3 Million Test Results From 2001 - 2005 From the Nation's Largest Database of Clinical Lab Results

LYNDHURST, May 3 2006 (PRNewswire) - People with diabetes who visit health professionals are doing a better job of managing their disease, according to results from the Quest Diagnostics Health Trends (TM) Diabetes Report. However, the Report also found that nearly half of all test results in 2005 were still above the target goal for diabetes control set by the American Diabetes Association (ADA).

The Health Trends Diabetes Report is based on 14.3 million hemoglobin A1c test results performed from 2001 through 2005 by Quest Diagnostics laboratories in the United States on patients whose physicians classified them as having diabetes through the use of specific diagnostic (ICD-9) codes. The proportion of test results deemed to represent good diabetes control increased from 36 percent in early 2001 to a high of 56 percent in late 2005, according to the Quest Diagnostics Report.

Quest Diagnostics Health Trends reports identify and track disease and wellness benchmarks. They are made available as a public service to inform patients, health professionals, and policy-makers about the current status of the nation's health. The Diabetes Report is the second in the series of Health Trends reports, following the Heart Health Report on LDL cholesterol levels, which Quest Diagnostics issued in October 2005.

The test for hemoglobin A1c (HbA1c) is a key indicator of diabetes control. It measures the amount of sugar attached to hemoglobin, the primary protein in red blood cells and indicates a patient's average blood sugar level over the previous two to three months. The ADA recommends that people with diabetes maintain their hemoglobin A1c levels below 7 percent of the total hemoglobin in red blood cells. The Health Trends Diabetes Report showed that the average hemoglobin A1c test result decreased from 7.8 percent of total hemoglobin in January 2001 to 7.2 percent in December 2005. This represents a drop of 8 percent.

"What makes these data so interesting is that they suggest that over time, glucose control is getting better," said Nathaniel G. Clark, M.D., M.S., R.D., National Vice President, Clinical Affairs, American Diabetes Association. "This is in direct contrast to the National Health and Nutrition Examination Survey (NHANES) data which suggests that diabetes control in the United States population declined through the period of the late 1990s. NHANES provides the context that makes the Quest Diagnostics data from the last five years so interesting."

"These results are a great contribution to our understanding of the state of diabetes care and outcomes in the United States," said Francine R. Kaufman, M.D., professor of pediatrics at the Keck School of Medicine, University of Southern California, and past president of the ADA. "They indicate that diabetes care has improved over the last five years with glucose-lowering agents, a push to multidisciplinary care, stricter criteria for diabetes diagnosis and public and professional awareness campaigns about the importance of early diagnosis and treating to target."

"Possible explanations are greater awareness of both the use of and goals for HbA1c, frequency of HbA1c testing and better use of available medications," said Dr. Clark, of the ADA.

The number of test results included in the Health Trends Diabetes Report is more than one hundred times that of other published reports on diabetes health. "This is a huge data set with enormous statistical power that helps us understand the state of control of diabetes in the United States," said David E. Goldstein, M.D., Professor Emeritus, University of Missouri Health Sciences Center, the first director of the national standardization program for HbA1c and principal investigator for the landmark Diabetes Control and Complications Trial. "This is valuable information for healthcare professionals, policy makers and payers."

"The Quest Diagnostics database not only is larger than any of the existing research studies but also provides more current data," said Josef Coresh, M.D., Ph.D., Professor of Epidemiology, Biostatistics & Medicine, Johns Hopkins University.

Most of the improvement in HbA1c results was observed within the first three years encompassed by the report. The reason for the slow-down in improvement in 2004 and 2005 is not known, but it could be attributed, at least in part, to the difficulty in getting closer to the goal as HbA1c results decrease. "As one approaches an HbA1c level of 7 percent it becomes harder and harder to make improvements," Dr. Clark said. "Moving from 10 percent to 9 percent is far easier than moving from 8 percent to 7 percent or lower."

On average, patients were tested 1.9 times per calendar year. This average testing frequency was the same in each of the five years. The ADA recommends that patients with stable diabetes control have their HbA1c measured twice a year. The vast majority of these tests were ordered by physicians in an office setting.

Another significant finding from the Quest Diagnostics Health Trends Diabetes Report is seasonal variation in HbA1c, with peak levels in winter months (December through February). This seasonal variation in HbA1c has been described. Climate and the decreased activity levels and higher food intake associated with the winter holidays have been mentioned as possible causes.

Diabetes is a growing health concern in the United States. More than 14 million Americans are currently diagnosed with diabetes and an additional 6 million may have diabetes and not know it, according to the U.S. Centers for Disease Control and Prevention. Diabetes is a chronic condition in which the body does not produce or properly use insulin to convert sugar into energy. If poorly managed or undiagnosed, diabetes may lead to serious complications including heart attack, stroke, blindness, amputation and kidney failure.

"There is a serious need for clinical baselines to determine how well we are succeeding at controlling this disease, and the Health Trends Diabetes Reports takes an important step in that direction by offering the first national set of clinical benchmarks," said Gary Puckrein, Ph.D., Executive Director of the National Minority Health Month Foundation in Washington, D.C.

The data used for Quest Diagnostics Health Trends reports consist of results of tests performed by Quest Diagnostics laboratories across the United States. Quest Diagnostics' database of aggregated results of patient testing data is the largest of its kind in the country.

"As the world of healthcare is looking to evidence-based medicine to drive better outcomes, we are proud to be able to use our large clinical database to provide quantitative insights into patient health," said Surya N. Mohapatra, Ph.D., Chairman and Chief Executive Officer, Quest Diagnostics. "Our Health Trends Diabetes Report demonstrates the power of our unique database to show important changes in the way that healthcare providers are helping people control their diabetes."

Study Methodology and Limitations

The Quest Diagnostics Health Trends Diabetes Report encompasses a sample of 14.3 million test results for people with diabetes who visited a health care provider and used a Quest Diagnostics laboratory during the years 2001 - 2005. It does not represent a random sample of the general population. It does not reflect the health of people who did not visit health professionals for diabetes or for whom HbA1c testing was not ordered. The Report excluded an additional 18.7 million hemoglobin A1c tests performed by Quest Diagnostics during the time period covered by the Report because the physician did not include the most commonly used diagnostic codes for diabetes (ICD-9 codes starting with 250) in the test order.

This study does not follow a cohort, but rather analyzes all test results for patients classified as having diabetes for whom any HbA1c test was performed over the five-year period, regardless of when their first test occurred during this period. Quest Diagnostics does not have access to clinical data that could help to explain the data trends, such as treatment prescribed.

As recommended by the ADA, the HbA1c testing method used by Quest Diagnostics throughout the five-year period is certified by the NGSP, the agency that ensures standardization of HbA1c testing worldwide, making results directly comparable to values from the Diabetes Control and Complications Trial.

Observed trends were consistent across geographic regions, and when analyzed by age and gender, suggested that there were no significant population or demographic changes to account for these trends.

Posted by dlife at 09:12 AM | Comments (0)

Antidepressant Medication May Prevent Recurring Depression in Diabetics

May 1, 2006 (Newswise) — The antidepressant sertraline may reduce the risk of recurrent depression and increase the period of time between episodes of depression in patients with diabetes, according to a study in the May issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

One of every four patients with diabetes experiences clinical depression, according to background information in the article. Among those with diabetes, depression can reduce quality of life and the ability to function and increase the risk for high blood sugar levels, diabetes-related complications and death. Treatment with antidepressant medications and psychotherapy has been shown to be effective, but only in the short term. In previous studies, one in seven patients with diabetes developed recurrent depression that did not respond to treatment and their blood sugar levels generally increased, placing them at a higher risk of complications associated with their diabetes.

Patrick J. Lustman, M.D., Washington University School of Medicine, St. Louis, and colleagues studied 152 patients with diabetes (average age 52.8 years) who had recovered from depression during treatment with sertraline. Participants were followed for up to one year or until their depression recurred, during which time 79 were randomly assigned to continue taking sertraline and 73 were randomly assigned to take a placebo. They visited a physician’s office every month and received phone calls at the two-week point to screen for symptoms of depression. If such symptoms were detected, they underwent a psychiatric interview. Patients’ hemoglobin (Hb A1c) levels, which reflect the individual’s control of blood glucose levels over the previous two to three months, were measured every two months.

Participants taking sertraline were significantly less likely to develop an additional episode of depression. After one year, 65.8 percent of the patients taking sertraline remained in remission from their depression, compared with 47.9 percent of those taking placebo. The amount of time that passed before depression recurred in one-third of the patients increased from 57 days among patients receiving placebo to 226 days among those taking sertraline. “Using data available at the one-year point, the number needed to be treated was six patients, i.e., it would be necessary to treat six patients to spare one patient from depression recurrence,” the authors write. All participants’ Hb A1c levels had decreased when they recovered from depression and remained lower as long as they remained depression-free, with no difference between the two study groups.

Depression is increasingly understood as a recurrent and debilitating disease, especially for those with diabetes, the authors write. Physicians suspect that the more time an individual spends depressed, the greater the risk for diabetic complications and death. “Our study establishes a clear benefit of sertraline for prevention of depression recurrence in patients with diabetes,” they conclude. “Sertraline lengthened the depression-free interval of maintenance and did not interfere with glycemic improvement achieved during the recovery phase. Treatment with sertraline is relatively simple, safe and widely available, and although it is not curative, it offers patients with diabetes a potentially viable method for ameliorating the suffering, incapacity and burden associated with recurrent depression.”

Posted by dlife at 09:24 AM | Comments (0)

National Survey Estimates Prevalence of Type 2 Diabetes Among Adolescents

May 1, 2006 (EurekAlert) - An estimated 39,000 U.S. adolescents may have type 2 diabetes and more than 2.5 million may have impaired fasting glucose levels, which could lead to diabetes and other health problems, according to a study in the May issue of Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals.

About 18.2 million U.S. citizens have diabetes, including 210,000 individuals younger than age 20 years, according to background information in the article. Type 2 diabetes, which occurs when the body cannot use the insulin that it manufactures to break down glucose in the body, is considered an emerging problem among this age group. Studies also indicate that impaired glucose tolerance, a blood glucose level that is higher than normal but not high enough for a diagnosis of diabetes, is common among young people who are overweight and can lead to the development of diabetes.

Glen E. Duncan, Ph.D., R.C.E.P.S.M., University of Washington, Seattle, used data from a national survey of the U.S. population to determine the prevalence of diabetes and impaired fasting glucose levels (which measure blood sugar after an eight-hour fast to detect impaired glucose tolerance) among U.S. adolescents. A total of 4,370 participants aged 12 to 19 (mean age 15.4) years were asked whether they had ever been told by a physician that they had diabetes. A subsample of 1,496 adolescents who responded "no" had their glucose levels testing after fasting overnight.

Of the 4,370 original participants, 18 or 0.5 percent had diabetes; of those, about 71 percent had type 1 diabetes and 29 percent had type 2 diabetes. About 11 percent, or 178, of the subsample without diabetes had impaired fasting glucose levels. When considered as a sample of the entire population of U.S. adolescents, these numbers are equivalent to 134,071 individuals age 12 to 19 years with diabetes, 39,005 with type 2 diabetes and 2,769,736 with impaired fasting glucose levels.

"The prevalence of type 2 diabetes and impaired fasting glucose levels is substantial among U.S. adolescents," Dr. Duncan concludes.

"These estimates have important implications for public health because of the high rate of conversion from impaired fasting glucose level to type 2 diabetes in adults and the increased risk of cardiovascular disease in individuals with type 2 diabetes."

Posted by dlife at 09:22 AM | Comments (0)

Children and Young Adults with Diabetes Do Not Meet Nutrition Recommendations

May 1, 2006 (EurekAlert) - Fewer than half of children and young adults who took part in a national multi-center study of young people with diabetes meet current dietary recommendations for many nutrients, potentially making treatment and management of their diabetes much more difficult, according to researchers at the University of South Carolina and other institutions.

The researchers analyzed at the nutrient intakes of nearly 1,700 10-to-22-year-olds who took part in the five-year nationwide SEARCH for Diabetes in Youth study. SEARCH is a multi-center study funded by the Centers for Disease Control and Prevention and the National Institute of Diabetes and Digestive and Kidney Diseases, focusing on children in the United States who have diabetes. Participants in the study had either Type 1 or Type 2 diabetes for at least 12 months.

The researchers found that less than half the participants met current dietary recommendations for total fat, vitamin E, fiber, fruits, vegetables and grains, "although a majority met recommendations for vitamin C, calcium and iron."

The researchers note that dietary recommendations for youth with diabetes "are based on strong scientific evidence regarding intake of specific nutrients and foods in relation to physiologic health outcomes, including appropriate growth and development through adolescent years and optimizing metabolic status…. Further work to better understand the barriers to healthful dietary habits and to identify effective approaches to improving dietary intake in youth with diabetes is urgently needed."

Posted by dlife at 09:20 AM | Comments (0)

New Study Results Show That Overweight Children Can Prevent Excess Weight Gain With Two Simple Steps

America On the Move(R) Family Study Provides Tangible Evidence that Small Changes Positively Impact Weight Gain Prevention in Children

SAN FRANCISCO, May 1, 2006 (PRNewswire) - The results of a new study provide the first clinical evidence that overweight children can effectively prevent additional weight gain by making small changes to their daily lifestyle. The America On the Move(R) Family Study, presented Sunday at the Pediatric Academic Societies Meeting in San Francisco, proves that this approach can help counter America's obesity crisis-one-third of all children in the United States are either overweight or dangerously close to becoming so and, as a result, are at increased risk of becoming obese adults and developing diabetes and other health problems.(1)

The study showed that over six months, 67 percent of families in the intervention group had children who maintained or reduced their percent body mass index (BMI) for age. Two hundred and sixteen families with at least one overweight child, as defined by BMI, the most widely accepted method of classifying overweight and obesity, participated in the study.(2)

"We are in a state of heightened attention about the issues of weight control and nutrition, as our nation's rate of obesity and diabetes expands to encompass younger generations," said Dr. James O. Hill, AOMF co-founder and professor of pediatrics and medicine at the University of Colorado at Denver and Health Sciences Center. "Healthy eating and active living is taught through parents, so it's critical that our study focused on supporting small changes in a family nutrition and physical activity context."

The randomized, single-blind cohort study-conducted by the University of Colorado at Denver and Health Sciences Center, the primary research arm for America On the Move Foundation(TM) (AOMF), a national nonprofit dedicated to helping individuals and communities across the country improve health and the quality of life-was designed to evaluate whether overweight children could reduce their risk of gaining additional weight through a combination of increasing physical activity by 2,000 steps daily and eliminating 100 calories, in part by replacing sugar in their diet with Splenda(R) No Calorie Sweetener, the most commonly used low calorie sweetener in the U.S. The small changes tracked over six months are the foundation of America On the Move(R), AOMF's flagship program.

"Based on the study's success, our hope is that more families will see America On the Move(R) as a fun and simple way to become more active, eat more healthfully and, as a result, achieve and maintain a healthy weight," said Dr. Hill. "Our results give parents ammunition to deliver a realistic and tangible way for the whole family to live healthier."

About the Study

The study was funded through a grant by the National Institutes of Health (NIH) and support from McNeil Nutritionals, LLC.(3) In the study, investigators randomized 216 families with at least one overweight child to either a lifestyle intervention group or a control group. Families in the intervention group were asked to eliminate 100 calories a day from their diet, in part by replacing sugar with Splenda(R) No Calorie Sweetener or consuming beverages made with sucralose, and increasing physical activity by 2,000 steps daily. Families in the control group were asked to monitor their diet and exercise levels. Food journals and pedometers were utilized to measure progress. After six months, significantly more overweight children in the intervention group maintained or reduced their percent BMI-for-age, compared to the self-monitoring group (67 percent versus 53 percent).

About America On the Move Foundation

America On the Move Foundation (AOMF) is a national nonprofit dedicated to helping communities across our nation make positive changes to improve the health and quality of life of all their citizens. The Foundation's flagship program, America On the Move (AOM), initiates and maintains meaningful and measurable individual, social, and environmental behavior changes that support healthy eating and active living habits. AOM's science-based programs provide the support and tools that help individuals of all ages manage weight effectively through energy balance-a balance of energy in calories consumed with the amount of energy burned through daily activity. AOM programs are implemented through communities, employer groups, schools and other organizations. PepsiCo's Smart Spot is the National Presenting Sponsor of the AOM program and America On the Move Day of Action. For more information, please visit http://www.americaonthemove.org/.

(1) Ogden, C.L. and Carroll, M.D. Prevalence of Overweight and Obesity in
the United States, 1999-2004. Journal of the American Medical
Association. 2006, 295 (Apr): 1549-1555.

(2) Splenda is a registered trademark of McNeil Nutritionals, LLC.

(3) The Surgeon General's Call to Action to Prevent and Decrease

See All May 2006 Articles.

Posted by dlife at 09:15 AM | Comments (0)