Landmark Study Highlights Complex Genetic Risk Factors Behind Type 2 Diabetes

April 27, 2007 (EurekAlert) - A UK collaboration of scientists has identified three new genes that predispose individuals to develop type 2 diabetes, bringing scientists a step closer towards understanding what causes this complex disease.

The study, jointly led by researchers at the University of Oxford and the Peninsula Medical School, Exeter, and forming part of the Wellcome Trust Case Control Consortium looked at over 2 billion pieces of genetic data and 6,000 people with type 2 diabetes and 8,000 controls to track down these three genes. In addition, they confirmed the link between the disease and a further two previously-identified genes.

The findings, published online today in the journal Science, bring the total number of genes known to be involved in type 2 diabetes to nine, including the FTO gene reported by the same UK group two weeks ago. The FTO gene influences individual risk of type 2 diabetes through its effect on weight and obesity.

Type 2 diabetes occurs as a result of a failure of the body to produce enough insulin to maintain normal levels of glucose (sugar) in the blood. This failure is usually compounded by a reduction in the capacity of the insulin released to work properly in tissues such as muscle and fat (known as insulin resistance). It is a major cause of heart disease and stroke, as well as blindness and kidney failure.

There are currently around 200 million people who have type 2 diabetes worldwide, yet its underlying cause is poorly understood, limiting both treatment and prevention. Lifestyle factors, such as poor diet and lack of exercise have been known for some time to increase risk of developing the disease, but scientists are becoming increasingly aware of the role played by genetics.

For each of the three genes described in the paper, the researchers have found that there are two common "versions", one of which is associated with an increased risk of developing type 2 diabetes, and the other with reduced risk. Each high-risk version increases the risk of type 2 diabetes by between 10 and 20 percent. All are common in the general population.

"This research helps us to understand that, for most people at least, an individual’s risk of developing diabetes as they get older is influenced by a number of genes, as well as by their environment," says Professor Mark McCarthy from the University of Oxford, one of the lead authors of the paper. "Clearly, the more 'high risk' alleles a person inherits, the higher the likelihood that they will go on to develop diabetes."

The exact role of the genes that have been implicated by these studies is still uncertain. However, two of them appear to be involved in the development, function and regeneration of insulin-producing beta cells, found within the pancreas. This finding is likely to help to answer a long-standing controversy in the diabetes field concerning the extent to which a reduced number of pancreatic beta-cells (as opposed to reduced function) contributes to the development of diabetes.

"We now have significantly more pieces to the jigsaw that will help us understand the mechanisms behind type 2 diabetes," says Professor Andrew Hattersley of the Peninsula Medical School, also a lead author on the paper. "Each piece of new knowledge takes us a step closer towards a future with improved prevention and treatment of this very significant condition."

The first important clues to the identities of these genes came from a genome-wide analysis conducted in 2,000 people with type 2 diabetes and 3,000 controls as part of the Wellcome Trust Case Control Consortium2. The Consortium is one of the biggest projects ever undertaken to identify the genetic variations that predispose people to or protect them from major diseases.

Professor Peter Donnelly of the University of Oxford, who heads the consortium said: "This landmark study reveals the power of the strategy that the Wellcome Trust Case Control Consortium has adopted to study diabetes and several other common diseases. It is clear that these and other findings which the Consortium will shortly be reporting will have a major impact on our understanding of the mechanisms behind many diseases of global importance."

These initial findings were then confirmed by studying a further 9,000 samples from the UK (the majority of them from the Dundee area collected by researchers from the Ninewells Hospital and Medical School.

The research has been conducted in close collaboration with two other groups from the US and Scandinavia, who were undertaking similar research studies in samples from Sweden and Finland. Their results, which have also identified the same three genes, are published today alongside the UK study. In a unique collaboration, these three international groups chose to combine forces rather than compete, resulting in the largest ever collaborative study of type 2 diabetes, involving over 32,000 subjects.

"The extraordinary achievements of this research project have only been made possible through the unique international collaboration," says Dr Mark Walport, Director the Wellcome Trust, which funded the UK study. "By sharing data and working together, the researchers have made significant progress in understanding the genetics underlying type 2 diabetes in a very short time."

Iain Frame, Research Manager at Diabetes UK, said: "Diabetes UK welcomes these exciting findings. It’s important to remember that Type 2 diabetes is a genetic condition and not just associated with lifestyle factors. This discovery will help us get closer to unravelling the genetics of the condition. If we can understand more about the genetics we can make real progress towards the prevention and treatment of Type 2 diabetes.

"Diabetes UK funded the original collection of samples at the beginning of this study. It is thanks to the collaborative efforts of Diabetes UK, a number of excellent researchers and the Wellcome Trust that this discovery has been possible."

Posted by dlifenews at 03:44 PM | Comments (0)

U of M-led Study Identifies New Genetic Risk Factors for Type 2 Diabetes

April 27, 2007 (EurekAlert) - Ten genetic variants associated with type 2 diabetes, a disease which impacts more than 170 million people worldwide, have been identified or confirmed by a U.S.-Finnish team led by scientists at the University of Michigan School of Public Health.

The discoveries could lead to the development of new drugs for diabetes, permit more effective targeting of drug and behavioral therapies, and help scientists and physicians better predict who will develop diabetes, said Michael Boehnke, the Richard G. Cornell Collegiate Professor of Biostatistics at the U-M School of Public Health.

Boehnke is the lead scientist on the Finland-United States Investigation of Non-Insulin-Dependent Diabetes Mellitus Genetics (FUSION) study group, which collaborated with two other groups of scientists to conduct the most comprehensive study to date of genetic risk factors for type 2 diabetes.

"Until recently we knew very little about the genetic architecture of type 2 diabetes," said Boehnke, adding that diabetes has been called 'the geneticist's nightmare' because there are so many behavioral and environmental factors---in addition to genes---that are risk factors for the disease. "This is certainly not the complete genetic architecture for diabetes, but we have come a long way in better understanding the genetic basis for this disease."

The groups identified at least four new genetic factors associated with increased risk of diabetes and confirmed the existence of another six. The findings of the three groups, published simultaneously today in the online edition of the journal Science, boost to at least 10 the number of genes confidently associated with increased susceptibility to type 2 diabetes.

"One of the nicest aspects of this study has been the collaboration between the three groups," Scott said. "Most of these variants would have taken substantially longer to identify if each group had proceeded independently."

Type 2 diabetes is characterized by high levels of blood sugar, caused by the body's inability to utilize insulin to move blood sugar into the cells for energy. Type 2 diabetes affects nearly 21 million in the United States and the incidence of the disease has skyrocketed in the last 30 years. Diabetes is a major cause of heart disease and stroke, as well as the most common cause of blindness, kidney failure and amputations in U.S. adults.

"By identifying these genes, we are identifying potential loci for drug action and suggesting classes of compounds that might be useful to help develop drugs to treat diabetes," Boehnke said.

In the study, researchers used a relatively new strategy known as a genome-wide association study, Boehnke said. Researchers began by scanning the genomes of more than 2,300 Finnish by typing more than 300,000 strategically selected markers of genetic variation. About half of the participants had type 2 diabetes and the other half had normal blood glucose levels.

To validate their findings, the researchers compared their initial findings with results from genome-wide studies of 3,000 Swedish and Finnish participants carried out by the Diabetes Genetics Initiative and 5,000 British participants done by the Wellcome Trust Case Control Consortium and UK Type 2 Diabetes Consortium. After identifying promising leads through this approach, the three research teams jointly replicated their findings by testing more focused sets of genetic markers in additional groups totaling more than 22,000 people from Finland, Sweden, Poland, the United States and the United Kingdom. All told, more than 32,000 people were tested for the study, making it one of the largest genome-wide association and follow-up efforts conducted to date.

"This achievement represents a major milestone in our battle against diabetes. It will accelerate efforts to understand the genetic risk factors for this disease, as well as explore how these genetic factors interact with each other and with lifestyle factors," said Elias A. Zerhouni, director of the National Institutes of Health. "Such research is opening the door to the era of personalized medicine. Our current one-size-fits-all approach will soon give way to more individualized strategies based on each person's unique genetic make-up."

The newly identified diabetes-associated variations lie in or near:

IGF2BP2. This gene codes for a protein called insulin-like growth factor 2 mRNA binding protein 2. Insulin-like growth factor 2 is thought to play a role in regulating insulin action.

CDKAL1. This gene codes for a protein called CDK5 regulatory subunit associated protein1-like1. The protein may affect the activity of the cyclin dependent kinase 5 (CDK5) protein, which stimulates insulin production and may influence other processes in the pancreas's insulin-producing cells, known as beta cells. In addition, excessive activity of CDK5 in the pancreas may lead to the degeneration of beta cells.

CDKN2A and CDKN2B. The proteins produced by these two genes inhibit the activity of cyclin-dependent protein kinases, including one that has been shown to influence the growth of beta cells in mice. Interestingly, these genes have been heavily studied for their role in cancer, but their contribution to diabetes comes as a complete surprise.

Chromosome 11. One intriguing association is located in a region of chromosome 11 not known to contain any genes. Researchers speculate that the variant sequences may regulate the activity of genes located elsewhere in the genome, but more work is needed to determine the exact relationships to pathways involved in type 2 diabetes.

The diabetes-associated genetic variants that were confidently confirmed by the new research are: TCF7L2, SLC30A8, HHEX, PPARG, KCNJ11 and FTO.

Posted by dlifenews at 03:41 PM | Comments (0)

Symptoms of Depression Associated with Development of Diabetes in Older Adults

April 24, 2007 (Newswise) — Older adults who have had symptoms of depression—whether those symptoms occurred once, increased or remained steady over a 10-year period—may be more likely to develop diabetes than those without depressive symptoms, according to a report in the April 23 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Previous research suggests that high levels of symptoms of depression, including irritability and trouble sleeping, are associated with increased risk of development of type 2 diabetes, according to background information in the article. However, with few exceptions, most of the studies have defined symptoms of depression based on a single survey filled out by participants. “Given the episodic nature of depression and depressive symptoms, a single self-report of symptoms may not fully characterize the association between depressive symptoms and diabetes,” the authors write.

Mercedes R. Carnethon, Ph.D., of Feinberg School of Medicine, Northwestern University, Chicago, and colleagues followed a group of 4,681 participants age 65 and older (average age 72.7) who did not have diabetes at the beginning of the study in 1989. Each year for 10 years, the participants were evaluated for the presence of 10 symptoms of depression, including those related to mood, irritability, calorie intake, concentration and sleep. Symptoms were scored on a scale of zero to 30, with scores of eight or higher indicating high levels of symptoms. Sociodemographic characteristics, clinical measures including height and weight, and information about medication use that would indicate the development of diabetes were also updated annually.

At the beginning of the study, the average depressive symptom score was 4.5, and one-fifth of participants had a score of eight or higher. During the follow-up period, scores increased by at least five points in nearly half the participants, and 234 individuals developed diabetes. Rates of diabetes were higher among those with a score of eight or higher, compared with those who had scores below eight.

“In this sample of older adults, a single report of high depressive symptoms, an increase in symptoms with time and persistently high symptoms over time are each associated with an excess incidence of diabetes,” the authors write. “Furthermore, increasing symptoms with time are associated with incident diabetes beyond initial high depressive symptoms and the association between increasing scores and incident diabetes was strongest among those with initially low baseline scores.”

These associations were not explained by considering other risk factors for diabetes, including physical activity, smoking and body mass index. “The pathophysiologic mechanism for this association remains unclear,” the authors write.

“Our findings in this population of older adults are of particular public health importance because there are 35 million U.S. adults older than 65 years,” they conclude. Because an estimated 2 million older adults experience depression or a related illness and 15.3 percent of those over 65 have diabetes, “findings from this study of a novel and highly prevalent risk factor for diabetes have important implications for a substantial subset of our population.”

Posted by dlifenews at 11:25 AM | Comments (0)

Lean for Life: Baby Formula That Fights Fat

April 23, 2007 (EurekAlert) - Infant formula and other baby foods that provide permanent protection from obesity and diabetes into adulthood could be on shop shelves soon, reports Lisa Melton in Chemistry & Industry, the magazine of the SCI.

The foods, under development at the Clore Laboratory at the University of Buckingham, will be supplemented with leptin, the hunger hormone. Those who take the foods early in life should remain permanently slim. 'Like those people who are lean by nature even though they overeat ? like we all do – they will tend to be inefficient in terms of using energy,' says Mike Cawthorne, who heads the Metabolic Research group at Clore.

Cawthorne's group has already demonstrated that supplementing infant rats' diets with leptin means that they never get fat or develop diabetes (AM J Physiol Regul Integr Comp Physiol, doi: 10.1152/ajpregu.00676.2006). Even animals fed a high-fat diet remained slim.

Leptin, the fat hormone that turns off hunger in the brain, is produced in the body throughout life. Its discovery was heralded as a major breakthrough, but research in adults proved disappointing because individuals soon seemed to resist its hunger-quenching effect.

But Cawthorne says this time things are different. Providing leptin earlier enough effectively hard-wires the body's energy balance. In fact, whether one is fat or thin may be determined before birth. Feeding the hormone to pregnant rats has been found to have a lifelong impact on their offspring's predisposition to obesity. Animals born of leptin-treated mothers remain lean even when fed a fat-laden diet, while those from untreated dams gained weight and developed diabetes.

The difference boils down to energy expenditure. The offspring of leptin-treated mothers burn up more energy. 'The infants are permanently inefficient in terms of using energy,' says Cawthorne.

Leptin-based products may also find their way into the pet obesity market.

Edinburgh researcher Jonathan Seckl says. 'We need to know whether leptin is acting pre- and post-natally, figure out how it works, and dissect the possible side-effects before this becomes a potential approach for humans. Nonetheless, this is good science,' he says.

Posted by dlifenews at 02:14 PM | Comments (0)

Standard Long-Acting Insulin as Good as Newer Medications

April 19, 2007 ( Eurekalert) - An older type of long-acting insulin is as effective in treating type 2 diabetes as newer and more expensive kinds, according to the results of a recent systematic review. However, the newer medications may cause fewer problems with low blood glucose while patients are sleeping.

People with type 2 diabetes who need insulin take once-a-day insulin for longer-lasting or "basal" control. (The review did not cover shorter-acting insulins used to control the blood glucose spike that comes from eating.)

Doctors consider the older medication, NPH, to be the current gold standard for basal insulin. Newer drugs, insulin analogues such as insulin glargine (trade name Lantus) and insulin detemir (Levemir), have been marketed as an improvement over NPH.

However, the reviewers found that Lantus and Levemir were almost identical to NPH in lowering levels of hemoglobin A1c, a widely used measure of long-term blood glucose control.

The eight studies analyzed had enrolled 2,293 people and were published in major medical journals. The studies lasted between 24 and 52 weeks.

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates research in all aspects of health care. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing trials on a topic.

The reviewers said their study indicated "only a minor clinical benefit" came from using the newer drugs for those with type 2 diabetes when they looked at overnight low blood glucose. They suggested a "cautious approach" when using Lantus or Levemir, at least until longer studies of the effectiveness and safety of the newer medications are completed.

Although NPH is less expensive than the other drugs, the reviewers could not come to any conclusion on cost-effectiveness or the effect of any of the drugs on quality of life. The relative impact on long-term complications such as blindness or kidney failure also was not clear.

"For the patient the good news is that the older medication works very well," said John Buse, M.D., president-elect of the American Diabetes Association. "In most people it will lower blood sugar with little risk of hypoglycemia. The review also shows that Lantus and Levemir had fewer problems with low blood sugar at night, giving greater security for those who experience this while sleeping."

Weight gain when starting insulin treatment is a concern because it can cause some to quit taking the medications if they feel they are getting fat.

"Levemir has been shown to cause less weight gain than NPH in several studies," said Buse, who was not involved with the Cochrane review. Two review studies did find that patients treated with the newer drug gained up to 3.5 pounds less than those on NPH.

Posted by dlifenews at 03:03 PM | Comments (1)

First Ever Study Predicts Outcome for Limb-Threatening Infections in diabetes

April 19, 2007 (EurekAlert) - Researchers from the University of Washington, Rosalind Franklin University of Medicine and Science, Merck Laboratories, and Mount Sinai School of Medicine have released a study suggesting that specific laboratory and clinical tests can predict outcome of antibiotic therapy for infections in persons with diabetes.

"This study is unique in a couple of ways," said Dr. David G. Armstrong, Professor of Surgery at Scholl’s Center for Lower Extremity Ambulatory Research (CLEAR) at Rosalind Franklin University. "It comes from the largest-ever clinical trial of antibiotics for this type of infection, and it used very specific, day-to-day measures that can be done in any hospital, world wide."

Among other findings, the study revealed that a bad outcome rose nearly five-fold for wounds that were either assessed as being deep, or those that were associated with a very high white blood cell count. Dr. Armstrong concluded that "Data from this study will now help us continue to move forward to better care for those patients who are most in need."

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

Disposable Insulin Nanopump From Debiotech and STMicroelectronics Marks Major Breakthrough in Diabetes Treatment

April 19, 2007 (PRNewswire-FirstCall) - Debiotech and STMicroelectronics (NYSE: STM) today announced a strategic cooperation agreement aimed at manufacturing and delivering to the market a unique miniaturized insulin-delivery pump. The Nanopump, which relies on microfluidic MEMS (Micro-Electro-Mechanical System) technology, is a breakthrough concept that allows a tiny pump to be mounted on a disposable skin patch to provide continuous insulin infusion. The Nanopump will enable substantial advancements in the availability, treatment efficiency and the quality of life of diabetes patients. The original technology was awarded the Swiss Technology Award in 2006 and this agreement brings it closer to the market.

Insulin pump therapy, or Continuous Subcutaneous Insulin Infusion (CSII), is an increasingly attractive alternative to individual insulin injections that must be administered several times a day. With CSII, the patient is connected to a programmable pump attached to a storage reservoir, from which insulin is infused into the tissue under the skin. Continuous delivery throughout the day, more closely mimics the natural secretion of insulin from the pancreas.

The highly miniaturized disposable insulin pump combines Debiotech's expertise in insulin delivery with ST's strengths in manufacturing high-volume silicon-based microfluidic devices. Microfluidic technology allows the flow of very small amounts of fluids to be electronically controlled. This pump represents a significant step in the development and adoption of CSII therapy and the leading-edge technology will also find applications in many other biomedical applications.

Today, existing insulin pumps are about the size of a pager. The new ST- enabled Debiotech miniaturized MEMS device is about one quarter the size of these existing pumps and can be worn as a nearly invisible patch on the skin. The small size frees the patient from concerns with holding the pump in place and concealing it under clothing.

The MEMS-based Nanopump also provides better control of the administered insulin doses. Dosing precision is a critical factor in treatment efficacy and contributes to reducing adverse long-term consequences. The Nanopump is able to control delivery at the nanoliter level, very close to the physiological delivery of insulin. The device prevents over-dosing and detects under-delivery, occlusion, air bubbles and other potential malfunctions in the pump to further protect patients. As a disposable device, manufactured using high-volume semiconductor processing technologies, the MEMS-based Nanopump will also be much more affordable, allowing the patient or the health system to avoid the typical up-front investment associated with current pump solutions.

The insulin Nanopump, developed by Debiotech and industrialized by ST, represents the first use of microfluidic MEMS technology in diabetes treatment. Functional samples have already been produced and the two partners expect that a fully industrialized product, in the form of a disposable cartridge, will be available in selected markets in 2008. Debiotech will remain responsible for the commercialization of the product through its licenses with major players in the medical device market.

The industrialization efforts will leverage STMicroelectronics' growing experience in the biomedical market. Other bio-tech programs within ST's Microfluidic Division include the In-Check lab-on-chip platform, currently being applied to the detection of sepsis and Avian flu.

"ST's increasing focus on applying its semiconductor manufacturing processes and growing experience in microfluidic biotech applications affords us the potential to improve lives for millions of people around the world," said Anton Hofmeister, Group Vice President and General Manager of ST's Microfluidic Division. "Working with Debiotech, a leading developer of innovative biomedical applications, we are committed to the industrialization of the insulin Nanopump that aspires to push the boundaries of diabetes treatment."

"This collaboration with ST represents a major step in manufacturing of the Nanopump to make it available to a broad market at a cost compatible with a unique disposable use. ST is a world leader in MEMS manufacturing and we are very excited to be working together to bring a real innovation to diabetic patients, offering a new way to treat one of the most severe diseases of our century," said Frederic Neftel, MD, President & CEO of Debiotech SA.

Posted by dlifenews at 10:53 AM | Comments (6)

ACP and ACP Foundation Launch Tools to Improve Diabetes Care

April 19, 2007 (EurekAlert) - Eat right. Exercise. Monitor blood sugar. Take medication regularly. This is the advice physicians give the more than 20 million Americans affected with diabetes. Yet implementation of these recommendations is often far from ideal, putting patients at greater risk for damage to the heart, kidneys, eyes, and feet.

In an effort to close this gap, the American College of Physicians (ACP) and the American College of Physicians Foundation (ACPF) are unveiling three practical tools for practicing internists who are ACP members, other healthcare professionals on clinical practice teams, and their patients.

These comprehensive educational tools are the culmination of an ambitious three-year Diabetes Initiative funded by an unrestricted educational grant from Novo Nordisk.

"The goals of providing these resources," said Vincenza Snow, MD, FACP, Director, Clinical Programs and Quality of Care at ACP, "are to increase awareness of the gap between current practice and acceptable standards of diabetes care; provide educational interventions to improve diabetes care; increase physician awareness of what constitutes high quality, evidence-based diabetes care; and recognize medical practices that improve their diabetes care."

The following materials are designed to help physicians and their staff to implement team-based care strategies, provide them with practical tools and motivate patients to implement lifestyle changes and self-management techniques.

• Living With Diabetes: An Everyday Guide for You and Your Family is an innovative model for patient education and empowerment. This self-management guide for patients covers diet, exercise, monitoring blood sugar, insulin, and other medications. Available with text in English or Spanish, Living With Diabetes is written in a conversational tone at a fifth-grade reading level and includes photographs of patients with diabetes and their families. It gives practical tips and concrete examples of successful approaches to control diabetes. Patients can get a copy of Living With Diabetes from their internist.

• The ACP Diabetes Care Guide for physicians and practice teams is intended to be used by multi-disciplinary teams providing care to patients with diabetes. It has two components: a printed practice manual (including special tools for better management of practice and patients) and a CD-ROM containing electronic versions of the manual and tools and 81 multiple-choice questions, answers, and critiques. One hundred thousand (100,000) copies of the guide will be distributed free to internal medicine physicians (including generalists and endocrinologists), nurses (including nurse practitioners), physician assistants, and diabetes educators (including nurses and dietitians). Health care professionals can use the guide to earn continuing education credits.

• The Diabetes Portal (http://diabetes.acponline.org) is a free Web-based resource for physicians and patients that provides tools, resources, and research supporting diabetes care. Patients and clinicians can access information specific to their needs. Clinicians can search for information under the headings of quality improvement, practice issues, and clinical topics. Information and links are updated regularly, providing clinicians and patients with the latest evidence-based guidance. Patient resources include information about eye, foot, heart, and kidney complications caused by diabetes, as well as portions of both the patient and physician guides listed above.

Both Living with Diabetes and the ACP Diabetes Care Guide can be ordered at http://diabetes.acponline.org and are free to ACP members.

"Diabetes is a dangerous disease that is growing annually," said Lynne M. Kirk, MD, FACP, president of ACP. "ACP and ACPF designed these resources - based on best-practices and evidence-based clinical guidance - to engage both physicians and patients to improve diabetes care in the United States."

In addition to the three Diabetes Initiative resources, a free CD-ROM of all diabetes-related presentations given at the previous three internal medicine annual meetings (2005-2007) will be distributed to ACP members. The CD-ROM will have audio and synchronized PowerPoint slides from the presentations and will allow users to share this educational program with other members of their diabetes care team.

Posted by dlifenews at 10:47 AM | Comments (0)

Columbia University Medical Researchers Find Diabetes May Be Linked With Cognitive Impairment

April 16, 2007 (MARKET WIRE) -- It is no secret that diabetes is linked with cardiovascular disease: the American Diabetes Association reports more than 65% of people with diabetes die from heart disease or stroke. Now, according to Columbia University Medical Center researchers, diabetes may be linked with an increased risk of cognitive impairment that may be a transitional step to Alzheimer's disease.

"Among cardiovascular risk factors, type 2 diabetes mellitus has been consistently related to a higher risk of Alzheimer's disease," the authors reported in the April issue of Archives of Neurology.*

The team studied 918 individuals 65 years and older who did not have mild cognitive disorder or dementia at baseline (between 1992 and 1994). At the beginning of the study and again every 18 months through 2003, each participant underwent an interview and assessment, which included physical and neurological examinations and cognitive tests.

During an average of 6.1 years of follow-up, 334 participants developed mild cognitive impairment. The researchers believed diabetes may be related to a higher risk for cognitive impairment by directly influencing the accumulation of plaques in the brain, which is a characteristic of Alzheimer's disease. In addition, cerebrovascular diseases such as stroke are related to both diabetes and Alzheimer's disease.
"Our results provide further support to the potentially important independent role of diabetes in the pathogenesis of Alzheimer's disease," the researchers concluded.

Studies published in peer-reviewed journals have reported that patients with heart disease, diabetes, and dementia (including Alzheimer's disease) may be deficient in vital nutrients: omega-3 (DHA and EPA) fatty acids, folic acid, and vitamins B6 and B12. Addressing these deficiencies may reduce cardiovascular risk.

Doctors are now using Animi-3® to reliably deliver, in a controlled, predictable manner, these nutrients to different patients. Animi-3 is a prescription supplement indicated for improving nutritional status in conditions requiring omega-3 (DHA and EPA), Vitamin B6, B12, or folic acid supplementation.

Ernst J. Schaefer, M.D., professor of medicine at Tufts University School of Medicine, is currently conducting a new double-blind, placebo-controlled study of Animi-3 for cardiovascular risk reduction and dementia. The Animi-3 clinical study is a six-month, double-blind, randomized, placebo-controlled trial in 75 subjects ages 55-80 years with no prior history of dementia.

"We believe subjects receiving the active supplement [Animi-3] will have significantly greater decreases in triglycerides, homocysteine, and small dense LDL, and greater increases in large HDL than those receiving the placebo," said Dr. Schaefer. "We are also studying the effects of this supplement on levels of C-Reactive Protein as well as measures of cognitive function, including memory and executive function."

"PBM Pharmaceuticals acknowledges this new development in diabetes research, which seems to be an additional reason for doctors to consider Animi-3 for diabetic patients," added company President Jack Schramm, inventor of the Animi-3 formula. "We eagerly await the results of the Animi-3 Dementia trial and believe supplementation benefits patients with these nutrient deficiencies."

Posted by dlife at 02:15 PM | Comments (0)

No Sign that Ethnic Groups' Genes Cause Diabetes, international Research Team Says

April 16, 2007 (EurekAlert) - A study by U.S. and Australian researchers is helping dispel the 40-year-old "thrifty genotype theory," which purports that certain minority groups are genetically prone to diabetes.

The study, co-authored by UC Irvine anthropologist Michael Montoya, along with an epidemiologist and population geneticist, analyzed existing genetic studies published across a variety of disciplines. The team found no evidence to support the widely held thrifty genotype theory, which suggests that cycles of feast and famine early in human history created a gene that helps the body use scarce nutrients – a gene that leads to obesity and diabetes in comfortable, sedentary modern lifestyles.

"Our study challenges the presumption that Native American, Mexican American, African American, Australian Aborigine, or other indigenous groups are genetically prone to diabetes because the evidence demonstrates that higher rates of diabetes across population groups can be explained by non-genetic factors alone," said Montoya. The study helps explain why more than 250 genes have been studied as possible causes of type-2 diabetes, but together these genes explain less than 1 percent of diabetes prevalence worldwide.

The findings are published in the spring issue of the journal Perspectives in Biology and Medicine.
"When it comes to diabetes, we're finding that genes are no more important for ethnic minorities than for anyone else," said Stephanie Fullerton, a population geneticist and bioethicist at the University of Washington and co-author of the study.

Also, it was found that in most existing studies of the suspected genes that contribute to diabetes in ethnic minorities, researchers failed to control for the potential impact of social and environmental factors. Controls would have enabled researchers to see that other factors – such as poverty, housing segregation or poor diet – were stronger indicators of diabetes than genes. "Our study shows that by focusing on genes, researchers miss the more significant and alterable environmental causes of diabetes," Montoya said.

Montoya argues that in order to gain a better understanding of the causes of type-2 diabetes, future research efforts will require interdisciplinary teams that assess social, historical and environmental factors as carefully as researchers have studied the genetic factors.

"Poor diet, reduced physical activity, stress, low birth weight and other factors associated with poverty all contribute to the high rate of diabetes in these groups," said Yin Paradies, epidemiologist at Australia's Menzies School of Health Research and co-author of the study.

Montoya's recent work has found that it's virtually impossible for geneticists to define ethnicity and race in strictly scientific terms – historic, political and social factors inevitably influence their definition of genetic groups. He is on faculty in the departments of anthropology and Chicano/Latino Studies in the School of Social Sciences. He is also on the faculty of UCI's Program in Medical Education for the Latino Community (PRIME-LC), the first medical education program in the country designed to meet the growing demand for physicians and public health leaders who are specifically trained to address the distinct and specific needs of medically underserved Latinos.

Posted by dlife at 02:04 PM | Comments (0)

Blame the Brain for High Blood Pressure

April 15, 2007 (EurekAlert) - The controversial idea that one cause of high blood pressure lies within the brain, and not the heart or blood vessels, has been put forward by scientists at the University of Bristol, UK, and is published this week in the journal Hypertension.

Dr. Hidefumi Waki, working in a research group led by Professor Julian Paton, has found a novel role for the protein, JAM-1 (junctional adhesion molecule-1), which is located in the walls of blood vessels in the brain.

JAM-1 traps white blood cells called leukocytes which, once trapped, can cause inflammation and may obstruct blood flow, resulting in poor oxygen supply to the brain. This has led to the idea that high blood pressure – hypertension – is an inflammatory vascular disease of the brain.

One in three people in the UK are likely to develop hypertension, and with 600 million people affected world wide, it is of pandemic proportions. The alarming statistic that nearly 60 per cent of patients remain hypertensive, even though they are taking drugs to alleviate the condition, emphasises the urgency of looking for new mechanisms by which the body controls blood pressure, and finding new therapeutic targets to drive fresh drug development.

Professor Paton said: “We are looking at the possibility of treating those patients that fail to respond to conventional therapy for hypertension with drugs that reduce blood vessel inflammation and increase blood flow within the brain. The future challenge will be to understand the type of inflammation within the vessels in the brain, so that we know what drug to use, and how to target them. JAM-1 could provide us with new clues as to how to deal with this disease. ”

Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation, commented: “This exciting study is important because it suggests there are unexpected causes of high blood pressure related to blood supply to the brain. It therefore opens up the possibility of new ways to treat this common, but often poorly managed, condition.”

As there is still poor understanding about what changes occur in people when hypertension develops, the finding of JAM-1 is of great interest and opens up multiple new avenues for further research and potential treatment.

Posted by dlife at 01:39 PM | Comments (0)

Happy Feet: 10 Tips for Maintaining Healthy Feet

April 13, 2007 (Newswise) — The human foot is a marvel of biomechanical engineering that most of us take for granted until the system fails or breaks down. The average person will walk the equivalent of twice around the world in a lifetime, which is a long time on your feet.

Podiatrists who are part of the UCLA Medical Group offer the following tips for helping maintain healthy feet and avoiding complications. The physicians are board-certified, provide comprehensive diagnosis and treatment of all foot and ankle conditions, and also have expertise in the management of diabetic foot problems and sports injuries.

10 Tips to Maintain Healthy Feet

1. Inspect your feet regularly and pay attention to changes in color, texture or appearance.

2. Maintain good foot hygiene, including washing and drying between the toes.

3. Hydrate the skin. Southern California weather and open shoes can cause rapid loss of moisture from the skin and may result in cracking or the formation of fissures. It is helpful to replace the moisture content by using lotions or creams on a regular basis.

4. Buy proper-size shoes. You may not wear the same size in shoes made by different manufacturers. Purchase new shoes late in the day, when feet tend to be at their largest. Always buy the shoes that feel the best.

5. Don’t ignore foot pain. Symptoms that increase or do not resolve within a reasonable period of time need to be evaluated by your podiatric physician.

6. Cut toenails straight across. Never cut into the corners — this could cause an ingrown toenail. Gently file away sharp corners or rough edges with an emery board.

7. Exercise. Walking is a great way to keep weight under control and is an excellent conditioner for the feet. Be sure to wear appropriate athletic shoes when exercising.

8. Alternate your shoes each day. Since the feet have sweat glands, your shoes will absorb moisture from your feet, so it is important to allow your shoes to dry out completely.

9. Avoid walking barefoot to help protect your feet from injury and infection.

10. Put sunblock on your feet while wearing sandals during the day to avoid sunburn.

Posted by dlife at 10:34 AM | Comments (1)

Study suggests use of stem cell transplantation is beneficial treatment of type 1 diabetes

April 11, 2007 (EurekAlert) A therapy that includes stem cell transplantation induced extended insulin independence in patients with type 1 diabetes mellitus, according to a preliminary study in the April 11 issue of JAMA.

Type 1 diabetes mellitus (DM) results from a cell-mediated autoimmune attack against pancreatic beta cells. At the time of clinical diagnosis, approximately 60 percent to 80 percent of the beta-cell mass has been destroyed, according to background information in the article. Beta-cell preservation has been shown to be an important target in the management of type 1 DM and in the prevention of its related complications.

Julio C. Voltarelli, M.D., Ph.D., of the University of São Paulo, Ribeirão Preto, Brazil, in collaboration with Richard Burt, M.D., of the Northwestern University Feinberg School of Medicine, Chicago, and colleagues conducted a study to examine the effect of high-dose immunosuppression followed by autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) to preserve beta-cell function in 15 newly diagnosed patients with type 1 DM. AHST, which uses a patient's own blood stem cells, involves the removal and treatment of the stem cells, and their return to the patient by intravenous injection.

During a 7 to 36-month follow-up, 14 patients became insulin-free (one for 35 months, four for at least 21 months, seven for at least six months; and two with late response were insulin-free for one and five months, respectively). Among those, one patient resumed insulin use one year after AHST. The only severe adverse effects were pneumonia in one patient and endocrine dysfunction in two others.

"This is, to our knowledge, the first report of high-dose immunosuppression followed by autologous nonmyeloablative hematopoietic stem cell transplantation for human type 1 DM. Very encouraging results were obtained in a small number of patients with early-onset disease. Ninety-three percent of patients achieved different periods of insulin independence and treatment-related toxicity was low, with no mortality. Further follow-up is necessary to confirm the duration of insulin independence and the mechanisms of action of the procedure. In addition, randomized controlled trials and further biological studies are necessary to confirm the role of this treatment in changing the natural history of type 1 DM and to evaluate the contribution of hematopoietic stem cells to this change," the authors conclude.

Related: Nancy Peolsi interview

Posted by dlifenews at 08:45 AM | Comments (3)

Report Reveals Estimated High Prevalence and Heavy Cost of Type 2 Diabetes Complications

April 10, 2007 (EurekAlert) – A first-of-its-kind report looking at the prevalence and cost of type 2 diabetes complications shows that an estimated three out of five people (57.9 percent) with type 2 diabetes have at least one of the other serious health problems commonly associated with the disease, and that these health problems are taking a heavy financial toll on the United States. In 2006, the nation spent an estimated $22.9 billion on direct medical costs related to diabetes complications.*

The new report, titled State of Diabetes Complications in America, also shows that estimated annual healthcare costs for a person with type 2 diabetes complications are about three times higher than that of the average American without diagnosed diabetes. These complications, which can include heart disease, stroke, eye damage, chronic kidney disease and foot problems that can lead to amputations, cost a person with type 2 diabetes almost $10,000 each year.* People with diabetes complications pay nearly $1,600 out of their own pockets for costs that are not reimbursed by insurance, such as co-payments and deductibles.* This amount is significant, considering that according to the National Health Interview Survey, an estimated 40 percent of adults with diabetes reported a family income of less than $35,000 per year in 2005.

Results from the report were released today at the American Association of Clinical Endocrinologists' (AACE) 16th Annual Meeting and Clinical Congress, by AACE in partnership with the members of a diabetes complications consortium: the Amputee Coalition of America, Mended Hearts, the National Federation of the Blind and the National Kidney Foundation, and supported by GlaxoSmithKline.

The State of Diabetes Complications in America is an analysis of national health and economic data specific to type 2 diabetes complications, and was developed as a follow-up to a 2005 AACE study showing that two out of three Americans with type 2 diabetes analyzed in a study had elevated blood sugar levels, which can lead to diabetes complications.

Many people with type 2 diabetes develop more than one health complication associated with the disease. The new report shows that an estimated one out of three people (33.3 percent) with the disease has one other serious health problem; one out of ten people (10.3 percent) with the disease has two other serious health problems; one out of 15 people (6.7 percent) with the disease has three other serious health problems; one out of 13 people (7.6 percent) has four or more other serious health problems.

"The report makes it clear that we have a major national issue when it comes to diabetes management, and that urgent action is needed," said Daniel Einhorn, MD, FACE, and Secretary of the Board of Directors of AACE. "People with type 2 diabetes need to achieve and maintain good blood glucose levels over time to improve their chances of reducing the risk of these serious complications."

The State of Diabetes Complications in America report synthesizes data from two large national studies to examine the issue of diabetes-related complications in the United States. Data on the prevalence of diabetes-related complications were derived from the National Health and Nutrition Examination Survey (NHANES) and combined with economic data from the Medical Expenditure Panel Survey (MEPS).

The report estimates that in people with diabetes, there are specific health problems that are more prevalent than in people with normal blood sugar levels. The prevalence of macrovascular problems, or those related to the heart and large blood vessels, in people with diabetes vs. people with normal blood sugar levels is as follows:

• Congestive heart failure occurs in 7.9 percent of people with diagnosed diabetes vs. 1.1 percent of people without diabetes

• Heart attack occurs in 9.8 percent of people with diabetes vs. 1.8 percent without diabetes

• Coronary heart disease occurs in 9.1 percent of people with diabetes vs. 2.1 percent without diabetes

• Stroke occurs in 6.6 percent of people with diabetes vs. 1.8 percent without diabetes

In terms of microvascular complications, which relate to small blood vessels, the prevalence is as follows:

• Chronic kidney disease (1) occurs in 27.8 percent of people with diabetes vs. 6.1 percent without diabetes

• Foot problems such as foot/toe amputation, foot lesions and numbness in the feet occur in 22.8 percent of people with diabetes vs. 10 percent without diabetes

• Eye damage (2) occurs in 18.9 percent of people with diabetes (figures for eye damage in people without diabetes are not available in NHANES)

While type 2 diabetes is closely tied to the development of these complications, it is possible that some people may have developed these health problems independent of their diabetes, due to family history or other underlying medical conditions.

"Beyond the impact on quality of life, health complications from type 2 diabetes also contribute to substantial national and individual healthcare costs," said Willard G. Manning, PhD, Professor, Harris School of Public Policy Studies at the University of Chicago. "My hope is that the report will call attention to the issue of diabetes-related complications and bring about change in the way we manage type 2 diabetes to help reduce both the physical and financial burdens."

Regarding annual healthcare costs for people with type 2 diabetes, heart attack is the most costly complication, at $14,150 per person, followed by chronic kidney disease (3) ($9,002); congestive heart failure ($7,932); stroke ($7,806); coronary heart disease ($6,062); foot problems (4) ($4,687); and eye damage (5) ($1,785).*

"As great as these financial burdens are, this is a conservative estimate, as it only includes direct medical costs," adds Manning. "Costs attributed to lost employment or productivity, premature death and disability have not been included, and if we factor in those costs, the overall burden would be far greater."

Posted by dlife at 11:46 AM | Comments (1)

Summer's Coming and People with Diabetes Need More than Sunglasses to Protect Their Eyes

April 9, 2007 (Joslin) -- The crack of the bat on Opening Day at Fenway Park is a sure sign that summer is on its way. From the Green Monster seats to the dunes of Cape Cod, summer means bright sun, ultraviolet rays and of course, sunglasses. But did you know that people with diabetes need more than sunglasses to protect their eyes?
Diabetes puts people at risk for cataracts, glaucoma and diabetic retinopathy, a leading cause of vision loss. But in the majority of cases, vision can be preserved if the disease is caught early and treated.
The experts at Joslin Diabetes Center's Beetham Eye Institute offer these quick reminders to keep your eyes in great shape not only in the summer but also all through the year:

• Diabetic eye disease can be painless until it reaches very advanced stages, and the earlier you can catch it, the more likely you can preserve your sight.
• You can have perfect vision and still have diabetic eye disease.
• An annual dilated eye exam can identify eye complications early on.
• If your doctor finds early signs of diabetic eye disease, a number of treatments may be recommended, including laser eye surgery, contact lenses, glasses and medications.
• Keeping your A1C (average monthly blood glucose levels) on target, controlling blood pressure and quitting smoking also can help preserve vision and prevent vision loss.

Joslin Diabetes Center has been on the cutting edge of diabetes-related eye disease prevention and care since its inception and has set standards across the world for the treatment and care of people with diabetes. With more than 360,000 people in Massachusetts diagnosed with diabetes, and thousands more having the disease and not knowing it, there is great risk of vision loss due to diabetic retinopathy. Comprehensive eye exams on an annual basis, proper management and care of your health, and of course, your favorite pair of sunglasses are all key to seeing your eyes in a new light. For an appointment at Joslin's Beetham Eye Institute, call (617) 732-2552. For more information on Joslin, visit http://www.joslin.org/.

Posted by dlifenews at 11:06 AM | Comments (0)

Joslin Diabetes Center-led Study Indicates Insulin Receptors Play a Critical Role in Promoting Islet Growth to Overcome Insulin Resistance

April 2, 2007 (Joslin) - A new Joslin-led study has identified the insulin receptor as an important protein that promotes islet cell growth in mice whose bodies are unable to use insulin properly, or are insulin resistant, a precursor to type 2 diabetes. Since the body's natural response to insulin resistance is to increase insulin secretion from the pancreas and grow more islet cells, also known as beta cells, harnessing this growth response could lead to new treatments for type 2 diabetes. The study appears in the early online edition of this week's Proceedings of the National Academy of Sciences.

"The failure to grow more functional beta cells (also called compensatory islet cell growth response) leads to overt diabetes," said Rohit N. Kulkarni, M.D., Ph.D., Investigator at Joslin Diabetes Center and Assistant Professor of Medicine at Harvard Medical School, who led the study. "If we can identify the key signaling proteins critical for the islet cell growth response, we can develop potential therapeutic targets to enhance the growth of beta cells."

There are two proteins that mediate the effects of growth factors in beta cells, the insulin-producing cells in the pancreas: insulin receptor, a protein that mediates the action of insulin, and IGF-1 receptor, another protein that closely resembles the insulin receptor and mediates the action of insulin-like-growth factor (IGF-I), a hormone and growth factor. These two receptors have been a major focus of research studies by Dr. Kulkarni and others at Joslin Diabetes Center who want to better understand beta cell growth and functioning so that these essential cells can be increased in people with diabetes.

In type 2 diabetes, the body doesn't produce enough insulin and/or is unable to use insulin properly (insulin resistance). This form of diabetes usually occurs in people who are over 40, overweight, and have a family history of diabetes, although today it is increasingly occurring in younger people, including adolescents. For reasons that are still unknown, islet cells malfunction in people with type 2 diabetes and their bodies are unable to compensate. By investigating the cellular mechanisms that affect islet cell growth and development, Joslin researchers hope to improve the process to better treat type 2 diabetes, the most common form of diabetes.

This study investigated whether insulin receptors in the beta cell play a key role in promoting their growth as a response to overcome insulin resistance. A state of transient insulin resistance occurs naturally during pregnancy and puberty, but without causing diabetes in most people because the beta cells are able to grow and secrete more insulin to easily overcome the insulin resistance. It is when the beta cells fail to grow and secrete more insulin in these states that overt diabetes develops.

Two mouse models were used in the study. In the first model, an insulin-resistant mouse was crossed with a mouse lacking insulin receptors in the beta cell. The resulting offspring had insulin resistance with no receptors in the beta cell. In spite of their insulin resistance, the mice didn't show an appropriate growth response in the islets because the beta cells lacked insulin receptors. "This provided genetic evidence that insulin receptors are important for the islet cell growth response to insulin resistance," said Dr. Kulkarni.

In the second part of the study, researchers examined the role of the two related receptors--insulin and IGF-1. They used two mouse models--beta-cell-specific insulin receptor knockouts (beta-IRKO), which lack insulin receptors in beta cells, and IGF-1 receptor knockout (beta-IGF1RKO), which lack IGF-1 receptors in beta cells. Both these mouse models were then compared to a control group of mice normally expressing both insulin and IGF-1 receptors in their beta cells. All three groups were placed on a high-fat diet to induce insulin resistance.

The researchers assessed the beta cell growth response in the pancreas: the beta-IRKO mice failed to show the growth of islet cells while the control and beta-IGF1RKO mice did exhibit this growth response. "The results clearly showed that it is the insulin receptor -- not the IGF-1 receptor -- that is critical for the islet cell growth response to insulin resistance," said Dr. Kulkarni.

Joslin researchers are working on a follow up study that aims to identify the proteins that control the signaling pathway. "We are excited about the possibilities to make further progress in this area," Kulkarni said.

Posted by dlife at 03:15 PM | Comments (0)

Glucose Triggers Brain Cell Death in Rats After Hypoglycemic Coma

April 4, 2007 (EurekAlert) - Brain damage that was thought to be caused by hypoglycemic coma actually occurs when glucose is administered to treat the coma, according to a study in rodents led by researchers at the San Francisco VA Medical Center.

The results are surprising, say the authors, and may be of clinical significance for the treatment of diabetics in hypoglycemic coma, though they caution that the results cannot be immediately extrapolated to humans.

Insulin is an essential hormone that moves glucose from the bloodstream to individual cells, where it is broken down and used for energy. Diabetics do not produce enough of their own insulin and must take it several times a day.
A severe insulin overdose can reduce levels of glucose in the blood to extremely low levels –– a condition known as hypoglycemia –– and cause hypoglycemic coma, resulting in destruction of neurons in the hippocampus and cerebral cortex, which are essential to memory and cognition.

"This study tells us for the first time that, in rats, the brain damage occurs not during the coma, but after it, when we give them glucose and their blood glucose levels return to normal," says principal investigator Raymond A. Swanson, MD, chief of the neurology and rehabilitation service at SFVAMC.

Furthermore, says Swanson, he and his fellow researchers have identified the cause of the damage: the sudden return of glucose to the brain activates the enzyme NADPH oxidase, which in turn initiates a process of oxidative stress that is fatal to neurons.

Oxidative stress occurs when cells are poisoned by highly reactive forms of oxygen. Previously, it had been assumed that oxidative stress in neurons was initiated primarily by mitochondria, which process oxygen for energy within cells.

The paper appears in the April 2007 issue of the Journal of Clinical Investigation.

In their study, the researchers subjected rodents to a model of severe hypoglycemic coma. "The rats could remain hypoglycemic without evidence of significant oxidative stress for at least 60 minutes," says Swanson, who is also professor and vice-chair of neurology at the University of California, San Francisco. "It was only when we gave them glucose to reverse the hypoglycemia that the oxidative stress occurred. This was a real surprise."
The researchers then discovered that oxidative stress and neuron death were prevented when the rats were given an inhibitor of NADPH oxidase, indicating a key role for this enzyme.

"It is well-established that mitochondria can be a source of oxidative stress," says Swanson. "But in this setting, oxidative stress comes from an entirely different source." He adds that the normal role of NADPH oxidase in the brain is "completely unknown."

The authors also found that the degree of oxidative stress was directly dependent upon the amount of glucose given. "We think that this stems from a known link between glucose and NADPH oxidase," Swanson says. "Glucose is a precursor for NADPH, which in turn is used by NADPH oxidase in generating oxidative stress."

Swanson explains that the results have implications for both basic and clinical science. For basic science, he says, "this calls for a reconsideration of our concepts about the causes of oxidative stress in other settings –– especially in ischemic stroke, where the blood supply to the brain is diminished and there’s a big burst of oxidative stress when the blood returns. That burst has always been blamed on oxygen, but it may be that glucose is the culprit. And it may depend on how much glucose is put in."

In terms of clinical science, Swanson observes that "as clinicians, our first reaction when we see a patient in hypoglycemic coma is to give lots of glucose, fast. But our rodent model makes it clear that overshooting glucose levels is very bad for rat brains. The way we treat patients for hypoglycemia may have to be reevaluated."

Swanson adds two strong cautions, however: "First, the work was done in rodents, and it is not legitimate to immediately extrapolate these findings to humans. Second, there are many ways to go wrong in humans by not treating hypoglycemia aggressively enough. The results of this one paper do not mean that clinicians should take an overly cautious approach to hypoglycemic coma."

In his own current research, Swanson is investigating the possible roles of glucose and NADPH oxidase as agents of oxidative stress in a rodent model of ischemic stroke. "So far, the results are very promising," he says.

Posted by dlife at 01:20 PM | Comments (1)

Penn study points to new direction for pancreas cell regeneration

April 4, 2007 (EurekAlert) – Replacing faulty or missing cells with new insulin-making cells has been the object of diabetes research for the last decade. Past studies in tissue culture have suggested that one type of pancreas cell could be coaxed to transform into insulin-producing islet cells.

Now, researchers at the University of Pennsylvania School of Medicine have demonstrated that these pancreatic acinar cells do not become insulin-producing cells in an animal model. However, they did show that injured pancreatic cells readily regenerate back into healthy acinar cells, which has implications for treating cancer and inflammation of the pancreas. This study appears in the April issue of the Journal of Clinical Investigation. The research also holds promise for new techniques for pancreas cell manipulation.

The pancreas is made up of two compartments with different functions: the islet compartment of insulin-producing beta cells and the much larger exocrine compartment composed of duct cells and acinar cells that make and deliver enzymes to the intestine for digestion. Diabetes is caused by the failure of the beta cells to make insulin, whereas pancreatic cancer usually originates from the exocrine compartment. Under certain conditions in tissue culture, acinar cells can synthesize insulin as well as amylase, a digestion enzyme.

"These findings have the potential to change the emphasis in diabetic research as far as regenerating the pancreas is concerned," says lead author Doris Stoffers, MD, PhD, Assistant Professor of Medicine.

Evidence from Stoffers' group and other groups is pointing to the beta cell itself as the most promising source for generating new beta cells. The focus of research is now shifting toward the direct stimulation of islet cell growth in live animals. In contrast, once acinar cells are removed from the organism and placed into culture, they may have greater potential to change into other cell types, including beta cells. As a result, Stoffers' animal model and technical approach is currently being used by other groups in the United States, Europe, and China to determine conditions under which acinar cells can take on the features of duct cells and beta cells.

The Penn team engineered mice with a special marker that permanently and selectively labels only pancreatic acinar cells. The mice were then subjected to pancreatic injury by chemicals or surgery. The pancreas was allowed to heal or regenerate itself, and the specific acinar cell marker was followed microscopically in thin slices of pancreatic tissue. "It is very clear that the acinar and islet compartments remain separate during regeneration in a live animal," says Stoffers.

"Although our work shows that acinar cells do not contribute to the insulin-producing compartment of the pancreas in an animal model, it is possible that other strategies might be successful in generating the islet cells," says Stoffers. Ongoing research is examining whether acinar cells from the mice used in this study can be induced to make insulin in tissue culture. "The hope is that these acinar cells would continue to make insulin after being transplanted back into the mouse," says Stoffers.

Posted by dlife at 10:30 AM | Comments (0)

Better Diabetes Awareness Doesn’t Equal Better Habits for Some African-Americans

April 3, 2007 (Newswise) — African-Americans who have family members with diabetes are more aware of the disease’s risk factors — but that awareness may not lead to a healthier lifestyle.

The type 2 diabetes epidemic disproportionately affects African-Americans, so researchers wanted to see whether having a family member with the disease had any influence on a person’s awareness or behavior. Their findings appear in the May issue of the American Journal of Public Health.

The study evaluated 1,122 African-American adults, living in Raleigh and Greensboro, N.C. None of the participants were diagnosed with diabetes; however, 36 percent reported that an immediate family member had the disease.
Participants where shown a seven-item list and asked whether any of the factors increase a person’s risk of developing diabetes. All seven items on the list are risk factors for diabetes — minority race or ethnicity, overweight, family history of diabetes, sedentary lifestyle, older age, high-calorie diet and diabetes during pregnancy.

Among the participants with a family history of diabetes, nearly 60 percent had a better- than-average awareness of the diabetes risk factors. About 47 percent of the participants with no family history demonstrated such awareness.

Yet, this awareness didn’t necessarily translate into healthy behavior.

“We hypothesized that persons with a family history would be more aware of risk factors for diabetes, however, we were surprised that they were not more likely to engage in more of the healthy behaviors compared to persons without a family a history,” said study co-author Tiffany Gary, Ph.D., of the Johns Hopkins Bloomberg School of Public Health.

More than 75 percent of the participants were aware that being overweight increases the risk of diabetes. But, of the 65 percent who were overweight, only 32 percent were trying to lose weight.

“Some reasons for this difference could be that people may not be aware of national standards used to define overweight and obesity,” Gary said. “Furthermore, it has been shown in several studies that there may be a greater acceptance of a heavier body size among African-Americans.”

So, what more can be done to raise awareness that being overweight can lead to dangerous health consequences?

“One approach would be to improve awareness of health risks associated with being overweight or obese and accurate perceptions of defining overweight and obesity,” Gary said. “This could be accomplished by national campaigns, community activism and policy approaches.”

Kate Lorig, R.N., a professor at Stanford University’s Patient Education Research Center said people who are overweight are “definitely aware that being overweight is unhealthy, but may not be able to name a specific risk.”

“Education is part of the answer,” Lorig said. “But what we really have to do is make it environmentally and educationally appealing to change behaviors, not just for diabetes, but for most chronic health conditions.”

The authors did find two areas of significant behavior difference. African-Americans with a family history of diabetes were more likely (26.9 percent vs. 20.4 percent) to eat five or more servings of fruits and vegetables daily and to have had a diabetes screening test (74.6 percent vs. 61.2 percent).

Posted by dlife at 04:02 PM | Comments (0)

FDA Approves JANUMET™ for Type 2 Diabetes

WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck & Co., Inc. announced today that the U.S. Food and Drug Administration (FDA) approved JANUMET™, the first and only tablet combining a dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin (also known as JANUVIA™), and metformin for the treatment of type 2 diabetes.

JANUMET has been approved, as an adjunct to diet and exercise, to improve blood sugar (glucose) control in adult patients with type 2 diabetes who are not adequately controlled on metformin or sitagliptin alone, or in patients already being treated with the combination of sitagliptin and metformin. JANUMET should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

The FDA approved JANUMET based upon clinical data including sitagliptin plus metformin as separate tablets. A clinical bioequivalence study has demonstrated the equivalence between JANUMET and sitagliptin plus metformin as separate tablets.

"JANUMET is the latest advance in Merck's longstanding commitment to developing effective medicines for type 2 diabetes," said Adam Schechter, president, United States Human Health, Merck & Co., Inc. "With JANUMET and JANUVIA, Merck now has a growing family of products that provides physicians with important treatment options for patients with type 2 diabetes."

JANUMET delivers proven efficacy

A 24-week, randomized, double-blind, placebo-controlled study with 701 patients with mildly to moderately elevated A1C levels (mean baseline 8.0 percent) inadequately controlled on metformin, showed that patients taking JANUMET2 (n=453) experienced significant additional mean placebo-subtracted reductions in A1C of 0.7 percent beyond that achieved by patients who continued on metformin alone (n=224) (p<0.001). In the study, more than twice as many patients on JANUMET (213 of 453 patients, or 47 percent) reached the American Diabetes Association's A1C goal of <7 percent compared with patients on metformin alone (41 of 224 patients, or 18 percent) (p<0.001).

JANUMET combines two agents with proven ability to deliver significant improvements in glycemic control: metformin, a commonly used effective glucose-lowering agent, and sitagliptin, a DPP-4 inhibitor that provides significant A1C lowering as monotherapy and as add-on therapy to metformin or thiazolidinediones (TZDs) based on clinical trials. JANUMET, like metformin, is dosed twice daily with meals. Consistent with the labeling for metformin alone, the labeling for JANUMET contains a boxed warning for lactic acidosis, a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with JANUMET.

"Physicians use several different medications in combination to address the multiple defects associated with type 2 diabetes, however, less than half of patients achieve and maintain their goal A1C levels," said Nir Barzilai, M.D., professor of Medicine and Molecular Genetics, director of the Institute for Aging Research, Albert Einstein College of Medicine. "JANUMET is an important new treatment option for many patients who need more than one therapy to control their type 2 diabetes because it addresses all three key defects of type 2 diabetes for improved glycemic control."

Patients treated with JANUMET experienced weight loss comparable to metformin alone, with no increased risk of hypoglycemia, edema, or GI disturbances beyond metformin alone

As clinicians select agents to add to the treatment regimens of patients with uncontrolled type 2 diabetes, it is important to consider issues such as weight gain, hypoglycemia, edema, and gastrointestinal disturbances.

In a 24-week study, mean body weight decreased 1.5 lb (n=399) in patients taking JANUMET, similar to patients taking metformin alone (1.3 lb decrease; n=169). There was no increased risk of hypoglycemia in patients treated with JANUMET (1.3 percent vs. metformin alone, 2.1 percent) and no increased risk of edema in patients treated with JANUMET (0.9 percent vs. metformin alone, 1.3 percent). In addition, there was no significant increase in the risk of overall gastrointestinal adverse reactions in patients treated with JANUMET (11.6 percent vs. metformin alone, 9.7 percent). Specific gastrointestinal adverse reactions included diarrhea (JANUMET, 2.4 percent vs. metformin alone, 2.5 percent), abdominal pain (JANUMET, 2.2 percent vs. metformin alone, 3.8 percent), nausea (JANUMET, 1.3 percent vs. metformin alone, 0.8 percent), and vomiting (JANUMET, 1.1 percent vs. metformin alone, 0.8 percent). The most common adverse experience in sitagliptin monotherapy reported regardless of investigator assessment of causality in ≥5 percent of patients and more commonly than in patients given placebo was nasopharyngitis.

Clinicians should be mindful that hypoglycemia could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents (such as sulfonylureas and insulin) or ethanol. Elderly, debilitated, or malnourished patients and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects.

By incorporating the novel mechanism of DPP-4 inhibition, JANUMET uniquely addresses the three key defects of type 2 diabetes

With the two active components, sitagliptin and metformin, JANUMET has a comprehensive mechanism of action that targets all three key defects of type 2 diabetes for improved glycemic control: diminished insulin release, uncontrolled production of glucose, and insulin resistance.

The sitagliptin component in JANUMET address two of the three key defects that cause poor glucose control: diminished insulin release due to beta-cell dysfunction and uncontrolled production of glucose by the liver due to alpha-cell and beta-cell dysfunction. By inhibiting the DPP-4 enzyme, sitagliptin significantly increases the levels of active incretin hormones, increasing the synthesis and release of insulin from the pancreatic beta cells and decreasing the release of glucagon from the pancreatic alpha cells.

JANUMET also contains metformin, which addresses the other key defect: insulin resistance. Metformin improves insulin sensitivity by increasing uptake and utilization of glucose by the muscles and tissues of the body. Metformin also decreases hepatic glucose production in a manner that is complementary to sitagliptin.

JANUMET provides powerful A1C lowering through combined reductions of both post-prandial glucose and fasting plasma glucose

JANUMET has been demonstrated to provide 24-hour glucose response - at mealtimes, between meals and overnight. In a 24-week, placebo-controlled study of patients with inadequate glycemic control on metformin alone, JANUMET significantly reduced post prandial, or post-meal, glucose (PPG) levels beyond metformin alone by a mean of 51 mg/dL in patients with a mean baseline 2-hour PPG of 275 mg/dL (n=387, p<0.001) and fasting plasma glucose levels (FPG) beyond metformin alone by a mean of 25 mg/dL in patients with a mean baseline FPG of 170 mg/dL (n=454, p<0.001).

Indications and contraindications for JANUMET

JANUMET is indicated, as an adjunct to diet and exercise, to improve glycemic control in adult patients with type 2 diabetes who are not adequately controlled on metformin or sitagliptin alone or in patients already being treated with the combination of sitagliptin and metformin. Consistent with the labeling for metformin alone, JANUMET is contraindicated in patients with renal disease, renal dysfunction, or abnormal creatinine clearance; and acute or chronic metabolic acidosis, including diabetic ketoacidosis. JANUMET should not be used in patients with type 1 diabetes.

Flexible dosing of JANUMET

JANUMET should be given twice daily with meals, with gradual dose escalation as needed to reduce the gastrointestinal (GI) side effects due to metformin. In this formulation, the dose of sitagliptin remains constant (100 mg daily) and is combined with the two most widely prescribed doses of metformin (1000 mg daily or 2000 mg daily). The recommended starting dose of JANUMET for patients not on prior metformin therapy and for those not adequately controlled on sitagliptin is 50 mg sitagliptin and 500 mg metformin twice-daily with meals. For patients already receiving metformin therapy, the starting dose should be based on the patient’s current metformin regimen. The total daily dose should not exceed 100 mg sitagliptin and 2000 mg metformin.

Metformin and sitagliptin are known to be substantially excreted by the kidney. The risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus, patients with serum creatinine levels above the upper limit of normal for their age should not receive JANUMET. In the elderly, JANUMET should be carefully titrated to establish the minimum dose for adequate glycemic effect, because aging can be associated with reduced renal function. Any dose adjustment should be based on a careful assessment of renal function. Before initiation of therapy with JANUMET and at least annually thereafter, renal function should be assessed and verified as normal.

Pricing and availability of JANUMET

The price of twice-daily JANUMET will be $4.86 per day. JANUMET will be broadly available in pharmacies in the near future.

Selected cautionary information for JANUMET

JANUMET should be avoided in patients with evidence of hepatic disease. Before initiation of therapy with JANUMET and at least annually thereafter, renal function should be assessed and verified as normal. Patients should be warned against excessive alcohol intake while receiving JANUMET. Patients may require discontinuation of JANUMET and temporary use of insulin during periods of stress and decreased intake of fluids and food such as may occur with fever, trauma, infection or surgery. Patients previously controlled on JANUMET who develop laboratory abnormalities or clinical illness should be evaluated promptly for evidence of ketoacidosis or lactic acidosis. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). When lactic acidosis occurs, it is fatal in approximately 50 percent of cases.

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