Study Using New Imaging Technology Detects Subtle Brain Changes in Patients With Type 1 Diabetes
January 31, 2006 (Eurekalert) - Although people with diabetes are twice as likely as the general population to develop depression, the cause of this increased risk is not well understood. Now, a Joslin Diabetes Center-led collaboration has documented for the first time subtle changes in the gray matter of the brain of type 1 diabetes patients compared to control subjects who did not have diabetes. They made these observations using voxel-based morphometry (VBM), a relatively new magnetic resonance imaging (MRI) technology that allows researchers to take very sensitive measurements of small regions in the brain. For the first time, doctors have reason to ask if the increased risk of depression could in fact be due to changes in brain.
"We have known for a long time that diabetes can damage the nerves that control the extremities and those that control internal organs like the heart and the intestine," says the study's principal investigator, Alan M. Jacobson, M.D., head of Behavioral and Mental Health Research at Joslin Diabetes Center. "This research helps document diabetes-related changes to the central nervous system. People tended to assume that the stress of dealing with a severe chronic illness and its complications was the sole source of depression. That still is an important issue, but now we have evidence that something else might be at work."
Equally important, by showing the effectiveness of VBM for observing and evaluating changes in brain structure that appear to be related to diabetes, the study opens up whole new approaches to understanding the central nervous system in diabetes. This technology creates three-dimensional images of magnetic resonance imaging data, which researchers can then use to observe and evaluate structural changes, in this case, in the brain.
"We've used this technology to look at patients with bipolar disorder or with classic neurodegenerative disorders, but this is the first study to use VBM to investigate brain changes in patients with diabetes," says co-investigator Perry Renshaw, M.D., Ph.D., who directs the Brain Imaging Center at McLean Hospital in Belmont, Mass.
For the study, the researchers measured gray matter densities in areas of the brain responsible for memory, language processing and attention. When they compared the images of 82 patients who had type 1 diabetes for 15 to 25 years with minimal complications to those of 36 age-matched control subjects who did not have diabetes, they discovered lower levels of gray matter density in the group with diabetes. Among that group, they also found that these lower levels in density were associated with poorer glycemic control and higher frequency of hypoglycemic events that led to unconsciousness.
"This study definitely does not mean that everyone who gets type 1 diabetes will suffer from clinically significant brain damage," Dr. Jacobson emphasizes. Indeed, he explains that in fact they observed little difference in cognitive function when patients with diabetes were compared to the participants in the control group. What is important, however, is the new tool researchers now have to examine what changes do occur, what drives them, and how they may affect brain functions, including those that lead to depression.
Understanding changes in brain structure becomes particularly critical as more and more people with type 1 diabetes are living longer lives, explains co-investigator Gail Musen, Ph.D., also of Joslin. "We want to be able to understand how the metabolic changes of diabetes affect the risks these patients face so we can find ways to minimize them as they go on to live 50 or more years with this disease."
Dr. Jacobson and his colleagues will continue now to follow the patients in the study to observe if and how the changes progress over time and whether high or low blood glucose influences that progression. Because they can also use MRI to measure the brain's response to stimuli like cognitive or emotional tests, they will also start looking at functional changes.
"Now that we've identified unexpected structural changes in the brains of people with diabetes, we need to understand more about how these relate to changes in brain function," says Dr. Renshaw. "The more we understand the problem, the better solutions we can find."
Posted by dlife at 11:52 AM | Comments (1)
Obese Children Twice as Likely to Have Diabetes
U-M researchers estimate more than 229,000 American children currently have diabetes; of those children, one-third are obese
January 30, 2006 ANN ARBOR, Mich. (UMHS Newsroom) – Childhood obesity can carry with it some heavy health risks that often last well into adulthood – heart disease, high blood pressure and depression, to name a few.
Obese children also are twice as likely to have diabetes than children who are of normal weight, according to a new study from the University of Michigan Health System.
The study, published in the February issue of Diabetes Care, is the most recent national study to estimate the prevalence of children with diabetes. It found that more than 229,000 children – approximately 3.2 cases for every 1,000 American children under the age of 18 – currently have diabetes. And one-third of those children are obese.
The study, was conducted by researchers with the Child Health Evaluation Research (CHEAR) Unit in the Division of General Pediatrics at the U-M C.S. Mott Children’s Hospital. It is based on data from the National Survey of Children’s Health (NSCH), a population-based household telephone survey sponsored by the Maternal and Child Health Bureau, the National Center for Health Statistics, and the Centers for Disease Control and Prevention.
As children’s waistlines have continued to grow so has concern that obesity will lead to even more children developing diabetes before they’ve graduated from high school. And caring for the combination of these children’s diabetes and obesity may place more strain on the health care system, says study lead author Joyce Lee, M.D., with the Division of Pediatric Endocrinology and CHEAR Unit at U-M.
"Among school-aged children, obese children have a greater than twofold chance of having diabetes, compared with children of normal weight,” says Lee.
“The large number of children with diabetes in the U.S., and the potential for increasing numbers of children developing diabetes with the obesity epidemic, has serious implications for how these children will receive appropriate health care now and as they grow into adulthood.”
For their study, Lee and her colleagues used a sub-set of information gathered from NSCH interviews with the parents and guardians of 102,353 children from January 2003 through July 2004.
As part of the interviews, the parents and guardians were asked if their child’s health care professional had ever told them that their child has diabetes.
The children were grouped into three categories based on their body mass index, or BMI: not overweight, overweight and obese. BMI was calculated using the height and weight of the child reported by his parent or guardian.
Children with a BMI above the 85th percentile for their age and sex are classified as overweight, while those with a BMI above the 95th percentile are considered obese. For example, a 10-year-old boy of average height would be defined as obese if he weighed approximately 101 pounds or greater, says Lee.
These data provided researchers with evidence of an association between childhood obesity and diabetes. The study found that children ages 6 to 11 and ages 12 to 17 who were obese were more than twice as likely to have diabetes than children of the same age who were of normal weight.
The study estimates that nationally, 229,240 children have diabetes. Prevalence of diabetes was higher among older children, and the disease was more common among non-Hispanic white children than non-Hispanic black or Hispanic children.
While one form of diabetes, type 2, is usually associated with obesity, data used for this study did not distinguish between the two types.
Still, results point to a greater need for public health strategies to curb childhood obesity and reduce the number of children with diabetes, says Lee.
“These data create cause for concern, especially with a nationwide shortage of specialists who care for children with diabetes,” notes Lee. “From a clinical, public health and health resources perspective, we need to address childhood obesity head-on to help reduce the future burden of diabetes in the U.S.”
In addition to Lee, Melissa L. McPheeters, Ph.D., MPH; and James G. Gurney, Ph.D., with the CHEAR team in the U-M Division of General Pediatrics; and William H. Herman, M.D., MPH, with the Department of Internal Medicine at the U-M Medical School and the Department of Epidemiology at the U-M School of Public Health, co-authored the study.
The study was funded by a National Institutes of Health Pediatric Health Services Research Grant.
Posted by dlife at 11:55 AM | Comments (0)
FDA Approves First Ever Inhaled Insulin Combination Product for Treatment of Diabetes
Pfizer's Exubera Approved for Type 1 and Type 2 Diabetes
January 27, 2006 - (FDA) There is a new, potential alternative for many of the more than 5 million Americans who take insulin injections, with the Food and Drug Administration's approval today of the first ever inhaled insulin. Exubera, an inhaled powder form of recombinant human insulin (rDNA) for the treatment of adult patients with type 1 and type 2 diabetes, is the first new insulin delivery option introduced since the discovery of insulin in the 1920s.
"Until today, patients with diabetes who need insulin to manage their disease had only one way to treat their condition," said Dr. Steven Galson, Director, Center for Drug Evaluation and Research, FDA. "It is our hope that the availability of inhaled insulin will offer patients more options to better control their blood sugars."
Diabetes is a disease that affects the amount of insulin and sugar in your body. Exubera is a human form of insulin and as such, lowers blood sugar concentrations by allowing the blood sugar to be taken up by cells as a source of fuel. Exubera is a powdered form of insulin that is able to be inhaled into the lungs through the patient's mouth using a specially designed inhaler.
There are two major types of diabetes — type 1 and type 2. People with type 1 diabetes produce virtually no insulin. In type 2, the most common form of the disease, the body does not produce enough insulin or effectively use insulin. If people with diabetes do not properly control their blood sugar levels, serious complications including heart disease, kidney failure, blindness, and nerve damage may develop.
The safety and efficacy of Exubera have been studied in approximately 2500 adult patients with type 1 and type 2 diabetes. In clinical studies, Exubera reached peak insulin concentration more quickly than some insulins, called regular insulin, administered by an injection. Peak insulin levels were achieved at 49 minutes (range 30 to 90 minutes) with Exubera inhaled insulin compared to 105 minutes (range 60 to 240 minutes) with regular insulin, respectively. In type 1 diabetes, inhaled insulin may be added to longer acting insulins as a replacement for short-acting insulin taken with meals. In type 2 diabetes, inhaled insulin may be used alone, along with oral (non-insulin) pills that control blood sugar, or with longer acting insulins.
Exubera prescriptions will be accompanied by a Medication Guide containing FDA-approved information written especially for patients. Pharmacists are required to distribute Medication Guides with products FDA has determined are important to health, and patient adherence to directions for use is crucial to the product's effectiveness. Patients are advised to read the entire Medication Guide and talk to their healthcare provider if they have further questions.
Like any insulin product, low blood sugar is a side effect of Exubera and patients should carefully monitor their blood sugars regularly. Other side effects associated with Exubera therapy seen in clinical trials included cough, shortness of breath, sore throat, and dry mouth.
Exubera is not to be used if you smoke or if you recently quit smoking (within the last 6 months). Exubera is not recommended in patients with asthma, bronchitis, or emphysema. Baseline tests for lung function are recommended before beginning treatment and are recommended to be repeated every 6 to 12 months thereafter.
While Exubera has been extensively studied for safety, the sponsor has committed to performing long-term studies to confirm the continued safety of Exubera after it is marketed and to examine more thoroughly the issue of the efficacy and safety of Exubera in patients with underlying lung disease.
Exubera is manufactured by Pfizer Inc., NY, NY.
Posted by dlife at 12:00 PM | Comments (0)
Weight Loss Improves Bladder Control in Women with Prediabetes
Diabetes Prevention Study Reveals Another Benefit of Lifestyle Changes
Janury 27, 2006 (NIH News) - Losing a modest amount of weight through dietary changes and increased physical activity reduces the occurrence of urinary incontinence (UI) in women with prediabetes, a condition in which blood glucose levels are higher than normal but not yet diabetic. This finding comes from a new study, published in the February issue of Diabetes Care, of women who participated in the Diabetes Prevention Program (DPP), a landmark clinical study funded by the National Institutes of Health (NIH).
Launched in 1995, the DPP’s main results were announced in 2001 and reported in 2002 (http://www.nih.gov/news/pr/feb2002/hhs-06.htm): losing 5 to 7 percent of weight through diet and a consistent increase in physical activity (e.g., walking 5 days a week 30 minutes a day) reduced the onset of type 2 diabetes by 58 percent. Treatment with metformin lowered the chances of developing diabetes by 31 percent.
“To combat the dual epidemics of obesity and type 2 diabetes, Americans need to know about the proven benefits of losing some weight through calorie reduction and increased physical activity,” said NIH Director Elias A. Zerhouni, M.D.
The DPP randomly assigned 3,234 overweight people with higher-than-normal blood glucose levels to one of three approaches to prevent type 2 diabetes: dietary changes and increased physical activity aimed at a 7-percent weight loss; treatment with the oral diabetes drug metformin; or placebo. The last two groups were also given standard medical advice about diet and weight loss. In the study, 660 women were randomly assigned to intensive lifestyle changes, 636 to metformin treatment, and 661 to placebo. Their average age was 50 years old, with an average body mass index of 35 (e.g., a 5’ 4” woman weighing 204 pounds).
Women who implemented intensive lifestyle changes and lost 5 to 7 percent of their weight had fewer episodes of weekly incontinence compared to those in the metformin or placebo groups (38 percent vs. 48 percent vs. 46 percent, respectively.)
“Our findings reinforce the DPP’s good news about the benefits of modest weight loss. A 200-pound woman who loses 10 to 15 pounds not only lowers the risk of developing type 2 diabetes but also improves bladder control,” said lead author Jeanette S. Brown, M.D., of the University of California, San Francisco. “If you’re a woman at risk for type 2 diabetes, preventing or delaying diabetes and improving bladder control are powerful reasons to make these lifestyle changes.”
Weight loss was particularly effective in reducing episodes of stress incontinence — leakage of small amounts of urine during physical movement, such as coughing, sneezing, and exercising. Stress incontinence results, in large part, from a weakening of the pelvic floor muscles that support the bladder. Though researchers do not fully understand all the factors contributing to stress incontinence, it is linked to obesity, diabetes, and other conditions, such as pregnancy, which increase pressure on the pelvic floor. In the DPP participants, weight loss did not alleviate urge incontinence — leakage of urine at unexpected times. Urge incontinence is more closely linked to overactive nerves that control the bladder, sometimes triggering inappropriate contractions.
More than 13 million people in the United States, mostly middle-aged and older women, experience loss of bladder control. Overweight women and those with type 2 diabetes have a 50- to 70-percent increased risk of incontinence. In the National Health and Nutrition Examination Survey 2001-2002 sample, one out of three women with diabetes or prediabetic glucose levels reported weekly or more frequent episodes of UI.
Some studies have reported that increased physical activity worsens incontinence, but DPP participants randomly assigned to lifestyle changes, who typically chose walking as their physical activity, did not have increased problems with incontinence.
“Urinary incontinence is a costly, socially isolating condition that impairs quality of life and takes a psychological toll on many women. For women at risk for type 2 diabetes, losing a modest amount of weight is likely to alleviate incontinence, especially stress incontinence,” said Leroy Nyberg, M.D., Ph.D., of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), which funded the study.
Nearly 21 million people in the United States — 7 percent of the population — have diabetes, the most common cause of blindness, kidney failure, and amputations in adults and a major cause of heart disease and stroke. Type 2 diabetes accounts for up to 95 percent of all diabetes cases. The prevalence of type 2 diabetes has risen dramatically in the last 30 years, due mostly to the upsurge in obesity. In addition, about 40 percent of U.S. adults ages 40 to 74 — 41 million people — have prediabetes, which raises the risk of developing type 2 diabetes and cardiovascular disease.
The NIDDK funds a great deal of research to improve the treatment and prevention of diabetes and urologic disorders. These efforts include the Urinary Incontinence Treatment Network (http://www.uitn.net/) and the Specialized Center of Research on Lower Urinary Tract Dysfunction in women, a multidisciplinary translational research center at the University of California, San Francisco (http://www.ucsf.edu/scor). Recently, NIDDK’s Central Repository (https://www.niddkrepository.org), which houses data collected in large clinical trials funded by the Institute, made data from the DPP available to researchers free of charge.
The NIDDK also sponsors "Let's Talk about Bladder Control for Women," a campaign to inform women about treatments for incontinence, from pelvic floor exercises to surgery. For more information, call 1-800-891-5388 or see http://www.niddk.nih.gov. The National Diabetes Education Program (http://www.ndep.nih.gov/), jointly sponsored by the NIH, the Centers for Disease Control and Prevention, and 200 partner organizations, is disseminating the DPP’s good news through its education campaign, "Small Steps. Big Rewards. Prevent type 2 diabetes." (http://www.ndep.nih.gov/campaigns/SmallSteps/SmallSteps_index.htm)
The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.
Posted by dlife at 11:57 AM | Comments (0)
Diabetes Complications Rooted in Faulty Cell Repair
UF researchers restore vitality to cells in lab experiments.
January 24, 2006 (EurekAlert) - University of Florida researchers say primitive cells that act like molecular maintenance men - traveling throughout the body to repair damaged blood vessels - become too rigid to move in patients with diabetes, fueling the disease's vascular complications. But they have found a way to restore the cells' flexibility, at least in the laboratory, according to findings published in the January issue of the journal Diabetes.
Having diabetes markedly raises the risk of developing a host of other ailments, from heart disease to stroke, blindness and kidney failure. Many arise after blood vessels suffer damage, spurring the accumulation of fatty deposits in the arteries or the wild, blinding growth of capillaries in the eye.
"We're interested in what happens in the body at the molecular level to cause these life-threatening problems," said Mark S. Segal, Ph.D., an assistant professor of nephrology, hypertension and transplantation at UF's College of Medicine. "Our work is focused on understanding why diabetic patients are at increased risk for these other diseases."
The problem is rooted in the body's response to vascular injury. The bone marrow churns out cells crucial to repairing the damaged lining of blood vessels. But sometimes they fail to report for duty.
"Part of the defect we think is occurring in diabetic patients is these cells do not carry out appropriate repair, and therefore these patients are at higher risk for cardiovascular disease and other complications," Segal said.
The inability of the cells to repair the peripheral vasculature, the large vessels of the body, is similar to their inability to repair the small vessels within the eye, he added.
"In the vasculature it leads to atherosclerosis, and within the eye it leads to diabetic retinopathy," he said. "So the link is we have one defect in these cells that can lead to both of these problems."
UF researchers isolated these repair cells from blood samples drawn from patients with diabetes and chronic kidney disease and studied them in the laboratory. The cells were unable to move about normally. But when nitric oxide gas was added, Segal said, the cells lost their rigidity, becoming suppler, and their ability to move dramatically improved.
In the body, nitric oxide occurs naturally. It helps the repair cells move out of the bone marrow where they are made, and it opens blood vessels and improves the uptake of oxygen. Patients with diabetes, however, commonly have low levels of nitric oxide.
"We went on to show that actually what's happening is nitric oxide is affecting the skeleton, or scaffold of the cell, and by adding nitric oxide we're able to rearrange the scaffold," Segal said. "When we rearrange the scaffold, the cells are able to migrate. The benefit of this is that when cells have improved movement they are able to repair the endothelium (the lining of the blood vessels) better and perhaps prevent atherosclerosis."
UF scientists suspect that in the cells taken from diabetic patients, nitric oxide interacts with a protein that steers the protein to the cell surface instead of inserting it into the cell as it would in healthy people. That causes the cell to stiffen.
The finding raises the possibility that nitric oxide could someday be used to keep the cells mobile, enabling them to travel to distant sites when needed, Segal said.
"The importance of this is related to other work that has shown that many drugs being used on the market today actually affect nitric oxide levels within these cells," Segal said. "So someday there may be two ways to help people whose cells may not function as well as they should. One is through certain medications - there may be a way we could actually give medications that would affect the nitric oxide levels within these cells and enhance their migratory ability. The other is through certain instances where we might actually collect these cells, treat them with nitric oxide outside the body and give them back to patients, to help improve the cells' migration ability."
In the future, for example, patients with diabetes and atherosclerosis who require angioplasty might receive injections of their own repair cells. The cells would be removed, incubated with nitric oxide to improve their function and then returned. They would theoretically help blood vessels heal more quickly, and perhaps keep new fatty deposits from forming, Segal speculated.
The research grew out of previous work at UF in collaboration with UF biochemist Daniel Purich, Ph.D., and pharmacologist Maria Grant, M.D. UF materials scientist Roger Tran-Son-Tay, Ph.D., among others, also participated in the current study.
"The work of Segal and colleagues is groundbreaking and provides important insights into the underlying mechanism of blood vessel damage in diabetes, which is the hallmark lesion for complications affecting the kidneys, eyes and nerves in patients with diabetes," said Anupam Agarwal, M.D., director of the Nephrology Research and Training Center at the University of Alabama at Birmingham.
Posted by dlife at 12:02 PM | Comments (0)
Metabolic Syndrome Identified As Risk Factor for Kidney-Pancreas Transplant Patients
WINSTON-SALEM, N.C., January 23, 2006 (Wake Forest University Baptist Medical Center ) – A three-year multi-center study of kidney-pancreas transplant recipients has identified a new risk factor for impaired kidney function, which may help physicians refine their treatment strategies.
Researchers from Wake Forest University Baptist Medical Center and colleagues reported their findings today at the 6th Annual American Society of Transplant Surgeons State of the Art Winter Symposium in Scottsdale, Ariz.
The researchers found that metabolic syndrome, a cluster of symptoms that increase the risk of heart disease, is also a risk factor for deterioration of kidney function in simultaneous kidney-pancreas transplant recipients. The risk is especially high when the pancreas transplant fails. The study involved 298 patients at 25 transplant centers.
“The findings suggest that we need to do whatever we can to keep the transplanted pancreas functioning because it may protect against development of long-term kidney transplant dysfunction,” said Jeffrey Rogers, M.D., a Wake Forest transplant surgeon. “The findings also underscore the importance of controlling weight, blood pressure, blood sugar and cholesterol – the variables that define metabolic syndrome.”
In kidney and pancreas transplantation, advances in immunosuppressive drug therapy have significantly reduced the risk of acute rejection. Transplant surgeons are now increasingly focused on developing strategies to prevent or slow a gradual deterioration in kidney function that can lead to the need for a second transplant.
Previous research had shown that metabolic syndrome is a risk factor for chronic deterioration of kidney function in kidney transplant recipients. However, the effect of metabolic syndrome on the outcome of simultaneous kidney-pancreas transplantation and the significance of having a functioning pancreas transplant in these patients has not been previously described.
About 700 kidney-pancreas transplants are performed each year in the United States. The procedure is performed in patients who have either type 1 or type 2 diabetes and kidney failure. The pancreas produces insulin, a hormone that helps regulate levels of blood sugar. People with diabetes do not produce enough insulin or cannot use insulin effectively. The primary function of the kidneys is to filter waste products and extra water from the body by producing urine.
Metabolic syndrome is diagnosed when someone has at least three of these following: body mass index greater than 30 or waist size larger than 40 inches for men or 35 inches for women, high levels of triglycerides, low levels of “good” cholesterol, high blood pressure or high levels of blood sugar.
The study followed 298 patients for three years after simultaneous kidney-pancreas transplantation. The researchers found that the prevalence of metabolic syndrome decreased from 59 percent prior to transplant to 19 percent one year after transplant. This would be expected because the transplant would eliminate diabetes – one of the components of metabolic syndrome.
Patients who had metabolic syndrome one year after transplant were 10 times more likely to have reduced kidney function three years after transplant than patients who did not have metabolic syndrome. The researchers analyzed how function of the transplanted pancreas affected the relationship between metabolic syndrome and kidney function and found that patients with metabolic syndrome who developed early pancreas transplant failure had the highest risk of developing long-term kidney dysfunction.
Rogers said that further study was needed to better understand the role a functioning pancreas transplant plays in preserving kidney transplant function in patients with metabolic syndrome so that long-term survival of both organs can continue to be improved.
Co-researchers were Robert Stratta, M.D., from Wake Forest, Agnes Lo, Pharm.D., from the University of Tennessee – Memphis, and Rita R. Alloway, Pharm.D., from the University of Cincinnati.
Posted by dlife at 12:15 PM | Comments (0)
deCODE Discovers Major Genetic Risk Factors for Type 2 Diabetes
Most Significant Inherited Component of T2d Yet Found; Discovery May Enable Development of Diagnostics and Drugs of Major Benefit to Public Health
REYKJAVIK, Iceland, Jan. 15, 2006 (PRNewswire-FirstCall) -- In a scientific paper published today a team of scientists from deCODE genetics and colleagues report the discovery of a variant in a gene on chromosome 10 that represents the most significant genetic risk factor for type 2 diabetes (T2D) found to date. More than one third of individuals in the populations studied carry one copy of the at-risk variant and are at an approximately 45% increased risk of the disease compared to controls; 7% carry two copies and are at a 141% greater risk. The original finding was made in Iceland and was subsequently confirmed in studies in Denmark and the United States. The paper is published today in the online edition of Nature Genetics at
http://www.nature.com/ng, and will appear in the journal's February print edition.
"This is a milestone in human genetics. A common gene variant conferring elevated risk of T2D has been earnestly sought by the genetics community for many years. We have found such a variant, which we estimate accounts for about 20% of T2D cases. This discovery sheds new light on the biological causes of the disease. Importantly, virtually all of this risk can be captured by looking at a single-letter change in DNA -- ideal for the development of a genetic test for assessing individual risk and developing more personalized and effective prevention strategies. This is also an exciting starting point for the discovery of new drugs, and we are actively pursuing the development of both diagnostic and therapeutic products to better prevent and treat T2D," said Kari Stefansson, CEO of deCODE and senior author on the study.
The variant is located in a gene encoding a protein called transcription factor 7-like 2 (TCF7L2). deCODE isolated the gene by following up on the results of a population-based, genome-wide linkage scan in Iceland that identified a promising region on chromosome 10. The deCODE team genotyped 228 microsatellite markers -- polymorphic signposts along the genome -- in this region in a total of more than 2000 patients and controls. Analysis of the frequency of different alleles, or versions, of these markers pinpointed a version of one marker within the gene encoding TCF7L2 that is approximately 1.5 times more common in patients than in controls. This corresponds to a 50% increase in risk of T2D per copy carried (there are two copies of each chromosome in every cell).
This finding was replicated in Danish and U.S. cohorts, where the at-risk version of the marker was found to confer an increased risk of 41% and 85%, respectively, per copy carried. For all of the cohorts combined, the at-risk allele confers an increase in risk of approximately 45% for those carrying one copy, and a 141% increase in risk for individuals carrying two copies. Utilizing data from the HapMap project, a SNP was found that correlates nearly perfectly with the at-risk microsatellite.
Diabetes: A major public health problem
Diabetes affects nearly 200 million people worldwide and an estimated 21 million in the United States -- 7% of the population. The vast majority of diabetes patients have type 2 diabetes, a condition where the body does not produce enough insulin and/or the cells in the body do not properly use insulin. In the United States, the direct medical cost associated with diabetes is nearly $100 billion per year. The incidence of type 2 diabetes is increasing rapidly in the industrialized world, in part due to the increase in obesity, one of the major risk factors for developing the disease.
About deCODE
deCODE genetics is a biopharmaceutical company applying its discoveries in human genetics to the development of drugs for common diseases. deCODE is a global leader in gene discovery -- our population approach and resources have enabled us to isolate key genes contributing to major public health challenges from cardiovascular disease to cancer, genes that are providing us with drug targets rooted in the basic biology of disease. deCODE is also leveraging its expertise in human genetics and integrated drug discovery and development capabilities to offer innovative products and services in DNA-based diagnostics, bioinformatics, genotyping, structural biology, drug discovery and clinical development. deCODE is delivering on the promise of the new genetics.(SM) Visit us on the web at http://www.decode.com.
Any statements contained in this presentation that relate to future plans, events or performance are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to a number of risks and uncertainties that could cause actual results to differ materially from those described in the forward- looking statements. These risks and uncertainties include, among others, those relating to technology and product development, integration of acquired businesses, market acceptance, government regulation and regulatory approval processes, intellectual property rights and litigation, dependence on collaborative relationships, ability to obtain financing, competitive products, industry trends and other risks identified in deCODE's filings with the Securities and Exchange Commission. deCODE undertakes no obligation to update or alter these forward-looking statements as a result of new information, future events or otherwise.
Posted by dlife at 12:21 PM | Comments (0)
Brain Plays Key Role in Diabetes Therapy
January 10, 2006 (Eurekalert) -The brain plays a major role in the ability of insulin therapy to lower blood sugar in animals with diabetes, according to a new study in the January 11, 2006, Cell Metabolism. "Our findings suggest that, in individuals with diabetes, the ability of insulin to lower blood sugar involves the brain," said senior author of the study, Michael Schwartz of the University of Washington at Seattle. "This effect is not trivial; the brain makes a substantial contribution to insulin response."
The findings in rats suggest that therapies that boost the brain response to insulin in patients with diabetes might improve blood sugar control while lowering the required dose of the hormone, the researchers said. That advance, in turn, might help to reduce side effects of insulin treatment, such as weight gain, they added.
Insulin normally allows body tissues, such as the muscles, to take up the blood sugar glucose, the body's prime energy source. In those with diabetes due to a lack of normal insulin or insulin resistance, blood sugar rises, a condition that can lead to tissue damage.
Scientists once thought that insulin's effects were limited to peripheral body tissues that respond to the hormone by importing glucose. However, more recent studies have revealed that insulin receptors in the brain also play an important role in normal blood sugar control.
To extend those findings to the disease state in the current study, the researchers examined the brain's effect on insulin sensitivity in rats with diabetes due to a lack of so-called pancreatic beta cells, which normally secrete insulin. The rats' condition mimics type I, or juvenile, diabetes, a form of the disease that begins in childhood most often due to autoimmune destruction of cells in the pancreas, which leave the organ unable to produce insulin.
The researchers infused the brains of the diabetic rats with a chemical that limits the function of an enzyme involved in the normal insulin response before injecting the animals with the hormone. Without the normal brain response to insulin, the hormone therapy's efficacy for reducing blood sugar fell by about 35%, Schwartz said. Furthermore, they found that gene therapy interventions designed to increase the brain's insulin response heightened the animals' response to therapy about 2-fold.
Posted by dlife at 01:46 PM | Comments (0)
Insulin Secreted by Embryonic Stem Cells Is Derived From External Sources, Concludes a Study in Cloning and Stem Cells
NEW ROCHELLE, N.Y, January 10, 2006,.(Business Wire) - Cultured embryonic stem cells induced to form insulin-producing Islet-like cell clusters--intended to replace the insulin production lost in diabetes--do not produce detectable amounts of new insulin, according to a report in the December 2005 (Volume 7, Number 4) issue of Cloning and Stem Cells, a peer-reviewed journal published by Mary Ann Liebert, Inc. The paper is available free online at www.liebertpub.com/clo.
Adding to the body of diabetes research aimed at developing a method to generate and transplant embryonic stem cells (ESCs) into patients with diabetes to replace pancreatic Islet cell function and insulin production, authors HJ Paek, Ph.D., and colleagues from Brown University (Providence, RI) reported on the results of studies that identified the origin of insulin secreted by Islet-like cell clusters (ILCCs) that were derived from ESCs. The researchers added human and bovine insulin to the mouse stem cells growing in culture to stimulate their differentiation into Islet-like cells. They then demonstrated that the insulin being secreted by the ILCCs was, in fact, not of mouse origin and not being made by the ILCCs, but was instead largely bovine or human insulin that the cells had taken up from the culture medium.
Depending on the culture technique used in these studies, the authors found that some of the mouse ILCCs did demonstrate the capacity to produce low levels of mouse insulin, offering hope that these techniques could be further developed and improved to increase insulin yield and make Islet cell transplantation a realistic treatment strategy in the future.
"These results provide clarification of a very important issue," says Ian Wilmut, Ph.D., Editor-In-Chief of Cloning and Stem Cells and Chair of Reproductive Science, University of Edinburgh. Islet-like cell clusters derived by the present procedures do not produce significant quantities of insulin. This result clarifies the challenge that remains."
Cloning and Stem Cells is an authoritative peer-reviewed journal published quarterly in print and online that focuses on understanding developmental plasticity and defining the molecular mechanisms that regulate differentiation or dedifferentiation of nuclei and cells. Tables of contents and a free sample issue may be viewed online at www.liebertpub.com/clo.
Mary Ann Liebert, Inc., is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Human Gene Therapy, Stem Cells and Development, and Tissue Engineering. Its biotechnology trade magazine, Genetic Engineering News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 60 journals, books, and newsmagazines is available at www.liebertpub.com.
Posted by dlife at 01:41 PM | Comments (0)
Obesity in Middle Age Raises Heart Disease, Diabetes Risk in Older Age
January 10, 2006 (Eurekalert) - Obesity in middle age – even without established cardiovascular disease risk factors such as high blood pressure or high cholesterol levels – greatly increases risk of hospitalization for and death from heart disease and diabetes in older age, according to a study in the Jan. 11 issue of the Journal of the American Medical Association.
Lijing Yan, assistant professor of preventive medicine, and colleagues at Northwestern University Feinberg School of Medicine assessed the relationship of body mass index (BMI) earlier in life with hospitalization for and death from cardiovascular disease and diabetes in older age (65 years and older). BMI is a measure of body fat based on height and weight.
Study participants were classified according to low, moderate, intermediate and high risk, based on blood pressure, treatment for hypertension, total cholesterol level, cigarette smoking and weight.
Of the 17,640 participants who had survived to age 65 and older, those who were overweight, and particularly those who were obese earlier in life, had significantly higher risks of hospitalizations for and death from heart disease and diabetes in older age compared with persons of normal weight with similar other cardiovascular risk factors at the beginning of the study.
Elevated risk was present for individuals both with and without other major cardiovascular risk factors, such as smoking in young adulthood and middle age.
In general, there was a consistent relationship in both men and women for hospitalization for and death from coronary heart disease, cardiovascular disease and diabetes in older age.
Study participants were men and women aged 31 through 64 years from the Chicago Heart Association Detection Project in Industry who were free of coronary heart disease, diabetes or major heart rhythm abnormalities at the beginning of the study in 1967.
The exceptionally long follow-up of the CHA study offered the researchers a rare opportunity to assess the long-term relationship between midlife BMI and health outcomes in older age, for which data are limited.
Results of the study showed that having a normal BMI in young adulthood and middle age confers significant health benefits at all levels of traditional risk factors.
"These outcomes are important to investigate in an era of population aging marked by an unprecedented large number of older adults resulting from aging of the baby boomers and from dramatic improvements in life expectancy for the entire population," said Yan.
"The study findings also strongly support the need for population-wide, multifaceted, primary prevention at young age of all risk factors, including overweight and obesity, as a key element for the national effort to continue the progress already achieved toward ending the epidemic of coronary heart disease and cardiovascular disease," the researchers said.
Posted by dlife at 12:28 PM | Comments (0)
National Institutes of Health Research on Obesity and Type 2 Diabetes
January 10, 2006 (Eurekalert) - Obesity in middle age – even without established cardiovascular disease risk factors such as high blood pressure or high cholesterol levels – greatly increases risk of hospitalization for and death from heart disease and diabetes in older age, according to a study in the Jan. 11 issue of the Journal of the American Medical Association.
Lijing Yan, assistant professor of preventive medicine, and colleagues at Northwestern University Feinberg School of Medicine assessed the relationship of body mass index (BMI) earlier in life with hospitalization for and death from cardiovascular disease and diabetes in older age (65 years and older). BMI is a measure of body fat based on height and weight.
Study participants were classified according to low, moderate, intermediate and high risk, based on blood pressure, treatment for hypertension, total cholesterol level, cigarette smoking and weight.
Of the 17,640 participants who had survived to age 65 and older, those who were overweight, and particularly those who were obese earlier in life, had significantly higher risks of hospitalizations for and death from heart disease and diabetes in older age compared with persons of normal weight with similar other cardiovascular risk factors at the beginning of the study.
Elevated risk was present for individuals both with and without other major cardiovascular risk factors, such as smoking in young adulthood and middle age.
In general, there was a consistent relationship in both men and women for hospitalization for and death from coronary heart disease, cardiovascular disease and diabetes in older age.
Study participants were men and women aged 31 through 64 years from the Chicago Heart Association Detection Project in Industry who were free of coronary heart disease, diabetes or major heart rhythm abnormalities at the beginning of the study in 1967.
The exceptionally long follow-up of the CHA study offered the researchers a rare opportunity to assess the long-term relationship between midlife BMI and health outcomes in older age, for which data are limited.
Results of the study showed that having a normal BMI in young adulthood and middle age confers significant health benefits at all levels of traditional risk factors.
"These outcomes are important to investigate in an era of population aging marked by an unprecedented large number of older adults resulting from aging of the baby boomers and from dramatic improvements in life expectancy for the entire population," said Yan.
"The study findings also strongly support the need for population-wide, multifaceted, primary prevention at young age of all risk factors, including overweight and obesity, as a key element for the national effort to continue the progress already achieved toward ending the epidemic of coronary heart disease and cardiovascular disease," the researchers said.
Posted by dlife at 12:25 PM | Comments (0)
Three-week Diet/Exercise Study Shows 50 Percent Reversal in Metabolic Syndrome, Type 2 diabetes
January 09, 2006 (Eurekalert) - Obese and overweight individuals suffering metabolic syndrome and Type 2 diabetes showed significant health improvements after only three weeks of diet and moderate exercise even though the participants remained overweight.
"The study shows, contrary to common belief, that Type 2 diabetes and metabolic syndrome can be reversed solely through lifestyle changes," according to lead researcher Christian Roberts of University of California, Los Angeles.
"This regimen reversed a clinical diagnosis of Type 2 diabetes or metabolic syndrome in about half the participants who had either of those conditions. However, the regimen may not have reversed damage such as plaque development in the arteries," Roberts said. "However, if Type 2 diabetes and metabolic syndrome continue to be controlled, further damage would likely be minimized and it's plausible that continuing to follow the program long-term may result in reversal of atherosclerosis."
"The results are all the more interesting because the changes occurred in the absence of major weight loss, challenging the commonly held belief that individuals must normalize their weight before achieving health benefits," Roberts said. Participants did lose two to three pounds per week, but they were still obese after the 3-week study.
The study, "Effect of a diet and exercise intervention on oxidative stress, inflammation, MMP-9, and monocyte chemotactic activity in men with metabolic syndrome factors," is in the online edition of the Journal of Applied Physiology published by the American Physiological Society. Researchers were Christian K. Roberts, Dean Won, Sandeep Pruthi, Silvia Kurtovic, and R. James Barnard, all of UCLA; Ram K. Sindhu of Charles R. Drew University, Los Angeles; and Nosratola D. Vaziri of University of California, Irvine.
The study involved 31 men who ate a high-fiber, low-fat diet with no limit to the number of calories they could consume. The participants also did 45-60 minutes of aerobic exercise per day on a treadmill.
Fifteen of the men had metabolic syndrome, a condition that is characterized by excessive abdominal fat, insulin resistance, and blood fat disorders such as high levels of triglycerides (fat in the blood) or low levels of HDL (high density lipoprotein, or "good" cholesterol). Thirteen of the participants had Type 2 diabetes. There was also some overlap between the two groups and some participants who had neither metabolic syndrome nor Type 2 diabetes, but were overweight or obese.
"The diet, combined with moderate exercise, improved many factors that contribute to heart disease and that are indirect measures of plaque progression in the arteries, including insulin resistance, high cholesterol, and markers of developing atherosclerosis," Roberts said. "The approach used in this experiment of combining exercise with a diet of unlimited calories is unusual."
Low-calorie foods
The participants in the current study, who ranged in age from 46 to 76 years old, took part in a 21-day residential program at the Pritikin Longevity Center, formerly in Santa Monica, combining the Pritikin diet and exercise program. The daily diet was low fat (12-15% of calories), moderate protein (15-20% of calories), and high in unrefined carbohydrates (65-70% of calories) and fiber (more than 40 grams).
Natural foods -- whole grains (five or more servings daily), vegetables (four or more servings), and fruits (three or more servings) -- were the main source of daily carbohydrates. The sources of protein were plants (such as soy, beans, and nuts), nonfat dairy (up to two servings daily), and fish and poultry (3.5-ounce portion once a week and in soups and casseroles twice a week). The remainder of the calories came from fat with a polyunsaturated-to-saturated fatty acid ratio of 2.4 to 1.
"Aside from meat and dairy, the study participants could eat as much as they wanted," Roberts said. "Because the food was not as high calorie as a typical American diet, the participants ate less before feeling full. This is a departure from most diets, which usually leave the dieter feeling hungry," he said.
The men also exercised daily on a treadmill, including level and graded walking, for 45-60 minutes. The exercise program was tailored to ensure each individual reached 70-85% of maximum heart rate.
Next steps
Trials outside the laboratory environment are needed to test the regimen in the general population. "The findings are likely generalizable, although the magnitude of change is proportional to the degree of abnormality when the person begins the regimen," Roberts added.
Scientists also need to determine whether long-term lifestyle change can prevent or reverse end-organ damage noted in those with metabolic syndrome or Type 2 diabetes, Roberts said. These changes may be difficult to make but the payoff for individuals and society could be enormous.
Further studies are also needed in those who are at risk for metabolic syndrome or Type 2 diabetes. Individuals should still be tested to see if Type 2 diabetes and metabolic syndrome can be prevented in the first place. Individuals may be considered healthy before developing metabolic syndrome but looking healthy does not necessarily mean being.
Posted by dlife at 01:49 PM | Comments (0)
The old saying “three out of five ain’t bad” might be true in sports. But when it comes to your heart, three out of five can definitely be bad. More doctors now agree that there are five basic factors that can lead to heart disease and diabetes – and that
January 3, 2006 (Newswise) — The old saying “three out of five ain’t bad” might be true in sports. But when it comes to your heart, three out of five can definitely be bad, says a University of Michigan expert.
More and more doctors agree that there are five basic factors that can lead to heart disease and diabetes – and that anyone with at least three of these characteristics is at especially high risk. Many Americans, even those who think they’re perfectly healthy, have at least three, says Melvyn Rubenfire, M.D., director of Preventive Cardiology at the U-M Cardiovascular Center.
Now, he and other heart experts are encouraging people to find out if they have those three to five “risk factors,” as they’re called, and to take action to reduce them. The good news is, many people can cut their risk and eliminate one or more risk factors with steps like better eating habits, more exercise and stopping smoking.
If more Americans knew their risks and did something about it now, he says, they might be able to avoid heart attacks, strokes, surgery, and lots of medications later.
The medical name for this collection of risks is metabolic syndrome, also sometimes called syndrome X. Recently, the American Heart Association published its first guideline for diagnosing and treating it. Although there’s some debate over exactly what test results a person should have to be diagnosed with metabolic syndrome, Rubenfire explains that there are five key risk factors to look at:
• Blood pressure that’s at or above 135/95, or that’s being lowered by drugs
• Weight, especially if it’s concentrated around the middle rather than the hips, causing a waist measurement over 40 inches (men) or 35 inches (women)
• Blood sugars over 100 on a test conducted in the morning before breakfast
• Triglycerides, a kind of fat in the blood, especially if it measures over 150
• “Good” cholesterol levels that are lower than 40 in a man or 50 in a woman
“None of these values is considered a major risk factor by itself,” Rubenfire explains. “They’re all actually normal values, but when put together, three or more of them constitute a very high risk.”
In fact, he says, these different factors seem to multiply one another, interacting in a way that makes a person more likely to have heart disease or develop diabetes in the future. People with metabolic syndrome are two to four times as likely to have a heart attack or stroke, and five times more likely to have diabetes over the long term.
Metabolic syndrome isn’t a disease, he explains, but rather a collection of warning signs that the body isn’t dealing well with the built-up effects of diet, lifestyle and inherited traits.
Blood pressure, for example, is actually a measurement of whether the walls of blood vessels have started to stiffen. Blood sugar in the morning, after a night of fasting, is a measure of how well the body is processing the carbohydrates that come in through food. If it’s high, it signals a condition called “insulin resistance” that means the body is losing its ability to absorb sugars from the blood.
Meanwhile, the triglyceride and “good” (HDL) cholesterol measurements show how well the body is coping with the amount of fat that comes in from food, and how likely it is that the fat is building up on the walls of blood vessels. And being overweight, especially around the middle of the body, puts a strain on the heart and blood vessels -- while also signaling that the body is getting more calories than it can burn and is storing them away as body fat.
People who have already been diagnosed with diabetes, or had a heart-related problem such as chest pain, can also have metabolic syndrome, and the risk of further problems that comes with it.
In his daily practice, Rubenfire treats many patients who have suffered heart attacks or chest pains and need drugs, surgery and rehabilitation to reduce their risk of further problems. About 60 percent of heart attack and stroke patients had metabolic syndrome, he says -- but most didn’t know it.
That’s why he and his colleagues have started a program for people who have three or more metabolic syndrome risk factors. Called MetFit, it guides participants through three months of exercise, diet counseling, medical testing, stress-reduction, and education.
But even without a special program, Rubenfire says, people who have metabolic syndrome can take action on their own, or with their doctor’s help. First things first, get tested, especially if you’re overweight or there’s a history of diabetes or heart disease in your family. Then, start making changes that are specific to your risk factors.
“The individual risk factors need to be treated no matter what, and they respond very, very well to lifestyle change,” he says. “Very often, it’s a lifestyle of physical inactivity, eating the wrong foods and too much of them, and genetic factors that contribute to this syndrome. The important thing is to change your lifestyle, so you can make a big impact on your risk factors and markedly reduce your risk of diabetes and heart disease.”
The specific steps to take are the same ones doctors have been telling heart and diabetes patients to do for years:
Exercise: Whether it’s walking, jogging, sports, aerobic dance or swimming, just moving more than you already do can make a big difference. If you’re not active now, find activities that you like and find time to do them. Exercise can help you burn calories, whittle away your body fat, and reduce your blood pressure, “bad” cholesterol and blood sugar.
Eat smarter: Choose foods that have “good” fats, reduce or eliminate foods that have cholesterol and sugar, and increase the amounts of fruits and vegetables and whole grains you eat. What you eat, and how much, can make a big difference in all of the metabolic syndrome risk factors.
Stop smoking: Smoking stiffens your blood vessel walls, causing your blood pressure to go up. It also aggravates the inflammation in your blood vessels that can combine with high cholesterol to create clots and plaque that can lead to chest pain, heart attacks and stroke.
Deal with stress: Stress can aggravate your blood pressure and get in the way of health. Identify the sources of stress in your life and take steps to reduce them or address them in a new way.
While you’re doing all of this for yourself, pay attention to the health of your children or grandchildren, too. Since many of the metabolic syndrome factors have links to our genes, they might have inherited risks from you and other members of your family.
One in 20 American kids has several metabolic syndrome risks factors already, Rubenfire says, but neither they nor their parents realize it. And with more and more kids, teens and young adults now weighing too much, eating too much and exercising too little, we’re setting our country up for an epidemic of metabolic syndrome and the heart disease and diabetes that will come from it. Rubenfire predicts that half of all Americans might have three of the five metabolic syndrome risk factors within a decade if the current trends aren’t reversed.
That change will have to start with individuals who decide to get tested, and doctors who make sure to test, he says. The sooner a person realizes that they’re at risk of heart disease and diabetes because of the “three out of five” risk factors, the sooner he or she can do something about it. “It’s a preventable problem,” he concludes. “We can prevent diabetes, we can prevent heart disease, and it doesn’t require medication. It requires only a change in your willingness to exercise and diet.”
About metabolic syndrome:
• Metabolic syndrome isn’t a disease, but rather a condition where a person has at least three of five “risk factors” that increase their chance of developing heart disease and diabetes.
• As many as one in five Americans may have three of the five metabolic syndrome risk factors, and most don’t know it. People who are overweight, especially those who carry that extra weight in their midsections, are most likely to have metabolic syndrome.
• The risk factors involve blood pressure, weight, blood sugar, blood triglycerides, and blood levels of HDL or “good” cholesterol. While there is some debate over the exact levels or measurements where risk begins, the general idea is that high-normal, and higher-than-normal, levels, are a concern – except in HDL cholesterol where higher is better.
For information on metabolic syndrome, the MetFit Program, and other heart-related treatment at the U-M Cardiovascular Center, call 888-287-1082.
Posted by dlife at 01:56 PM | Comments (0)
FDA Notified Healthcare Professionals About Post-Marketing Reports of New Onset and Worsening Diabetic Macular Edema for Patients Receiving Rosiglitazone
January 01, 2006 (FDA) - GlaxoSmithKline and FDA notified healthcare professionals about post-marketing reports of new onset and worsening diabetic macular edema for patients receiving rosiglitazone. In the majority of these cases, the patients also reported concurrent peripheral edema. In some cases, the macular edema resolved or improved following discontinuation of therapy and in one case, macular edema resolved after dose reduction.
As part of the ongoing efforts of GlaxoSmithKline (GSK) to provide updated information to health care providers, we would like to inform you of important new safety information regarding products containing rosiglitazone (i.e., Avandia®, Avandamet®, and coming soon in some markets, Avandaryl™). These products are anti diabetic therapies used in treating type 2 diabetes mellitus. To date, cumulative worldwide exposure is in excess of 5.3 million patients for Avandia and 769,000 patients for Avandamet.
GlaxoSmithKline has received very rare post-marketing reports of new onset and worsening diabetic macular edema for patients receiving rosiglitazone (Avandia or Avandamet). In the majority of these cases, the patients also reported concurrent peripheral edema. In some cases, the macular edema resolved or improved following discontinuation of therapy and in one case, macular oedema resolved after dose reduction.
Macular edema typically occurs in association with diabetic retinopathy, although it is more likely to occur as retinopathy progresses. Risk factors for macular edema include duration of diabetes, presence of retinopathy, hypertension, and poor glycemic control. Symptoms suggestive of macular edema include blurred or distorted vision, decreased color sensitivity, and decreased dark adaptation.
GSK is sending this letter in order to highlight this important new safety information and the precaution proposed by the company to be included in all rosiglitazone (i.e., Avandia, Avandamet and coming soon in some markets, Avandaryl™) product information for prescribers and patient information leaflets.
GlaxoSmithKline is committed to providing Health Care Providers and patients with the most up-to-date and accurate information regarding our products. Should you have any questions or require additional information, please contact your local GSK information line.
Posted by dlife at 01:54 PM | Comments (0)