The Traditional Mediterranean Diet Protects Against Diabetes

May 29, 2008 (EurekAlert) - The traditional Mediterranean diet provides substantial protection against type 2 diabetes, according to a study published on bmj.com today.

The Mediterreanean diet is rich in olive oil, grains, fruits, nuts, vegetables, and fish, but low in meat, dairy products and alcohol.

Current evidence suggests that such a diet has a protective role in cardiovascular disease, but little is known about its role on the risk of developing diabetes in healthy populations.

The SUN prospective cohort study involved over 13 000 graduates from the University of Navarra in Spain with no history of diabetes, who were recruited between December 1999 and November 2007, and whose dietary habits and health were subsequently tracked.

Participants initially completed a 136 item food frequency questionnaire designed to measure the entire diet. The questionnaire also included questions on the use of fats and oils, cooking methods and dietary supplements.

Every two years participants were sent follow-up questionnaires on diet, lifestyle, risk factors, and medical conditions. New cases of diabetes were confirmed through medical reports.

During the follow-up period (median 4.4 years) the researchers from the University of Navarra found that participants who stuck closely to the diet had a lower risk of diabetes. A high adherence to the diet was associated with an 83% relative reduction in the risk of developing diabetes.

Interestingly, those participants who stuck strictly to the diet also had the highest prevalence of risk factors for diabetes such as older age, a family history of diabetes, and a higher proportion of ex-smokers. This group of participants was therefore expected to have a higher incidence of diabetes, but this was not the case. If fact, say the authors, they had a lower risk of diabetes, suggesting that the diet might provide substantial protection.

The major protective characteristics of the diet include a high intake of fibre and vegetable fat, a low intake of trans fatty acids, and a moderate intake of alcohol. In addition, a key element of the diet is the abundant use of virgin oil for cooking, frying, spreading on bread, and dressing salads.

The authors conclude by calling for larger cohorts and trials to confirm their findings.

Posted by dlife at 10:49 AM | Comments (3)

Diabetes Doubles Liver Cancer Risk for Patients With Advanced Hepatitis C

May 29, 2008 (EurekAlert) - Patients who have chronic hepatitis C with advanced fibrosis have twice the risk of developing liver cancer if they also have diabetes. These findings are published in the June issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD). The article is also available online at Wiley Interscience (www.interscience.wiley.com).

Recent studies have suggested that diabetes increases one’s risk for hepatocellular carcinoma (HCC), also known as liver cancer, possibly because diabetes often occurs as part of the metabolic syndrome, which increases the risk of non-alcoholic steatohepatitis (NASH), which can lead to liver cancer. Chronic hepatitis C also increases the risk of liver cancer, so patients who have both diabetes and hepatitis C have two pathways through which HCC might develop.

Researchers led by Bart Veldt and Harry Janssen of the Erasmus MC University Medical Center in the Netherlands, aimed to quantify the liver cancer risk of patients who have both diabetes mellitus and advanced hepatitis C. They used data from five large hepatology units in Europe and Canada and included 541 consecutive patients between 1990 and 2003 who had chronic hepatitis C and advanced liver fibrosis or cirrhosis as shown by liver biopsy. For each patient, they gathered demographic, clinical, biochemical and virological data, along with fibrosis assessment and details of hepatitis C treatment.

Eighty-five of the 541 patients included in the study had diabetes. Patients with more severe fibrosis were more likely to be diabetic. “The prevalence of diabetes mellitus was 10.5 percent for patients with Ishak fibrosis score 4, 12.5 percent for Ishak-score 5 and 19.1 percent for Ishak-score 6,” the authors report.

During the median follow-up time of four years, 11 patients (13 percent) with diabetes vs. 27 patients (5.9 percent) without diabetes developed hepatocellular carcinoma. The 5-year occurrence was 11.4 percent and 5.0 percent, respectively. Male gender and older age were significantly associated with elevated HCC risk. “In addition, there was a strong trend towards a higher incidence of HCC among patients with diabetes mellitus,” the authors report. Multivariate Cox regression analysis of patients with Ishak 6 cirrhosis showed that diabetes was independently associated with the development of HCC.

Interestingly, among patients with diabetes, there was a trend towards higher risk of HCC as fasting glucose levels increased. The authors hypothesize that resulting hyperinsulinemia might help explain the increased risk of HCC among diabetic patients.

Whatever the mechanism, the risk is clear. “For patients with chronic hepatitis C and advanced cirrhosis, diabetes mellitus increases the risk of developing HCC,” the authors conclude.

Posted by dlife at 10:48 AM | Comments (0)

Special Supplement on Self-Monitoring of Blood Glucose in Diabetes Technology & Therapeutics

May 29, 2008 (EurekAlert) - Subjects with type 1 or type 2 diabetes who self-monitor their blood glucose levels more frequently and use the results to adjust treatment regimens can achieve improved glucose control, according to a collection of state-of-the-art reports that comprise a Special Supplement to the June 2008 issue (Volume 10, Supplement 1) of Diabetes Technology & Therapeutics, a peer-reviewed journal published by Mary Ann Liebert, Inc. (www.liebertpub.com). The supplement is available free online at http://www.liebertonline.com/dia

"Increased frequency of self-monitoring of blood glucose (SMBG) has been shown to significantly improve glucose control. SMBG not only complements A1C results, it guides the patient for self-management of diabetes at home on a day-to-day basis," writes Editor-in-Chief, Satish K. Garg, MD, Professor of Medicine and Pediatrics at the University of Colorado at Denver and Health Sciences Center, in a supplement overview.

Spanning the clinical, practical, and economic implications of SMBG, the supplement includes papers probing the technology behind state-of-the-art glucose meters and self-monitoring techniques, SMBG in pregnancy, and SMBG in the Asia-Pacific Region.

Shoba Subramanian, MD, and Irl Hirsch, MD, of the University of Washington, Seattle, review the evidence supporting frequent SMBG, recent advances in glucose meters and SMBG data processing and how it can be applied for more effective type 1 diabetes management, as well as the potential barriers to use of frequent SMBG that limit its applicability, in an article entitled, "The Utility and Recent Advances in Self-Monitoring of Blood Glucose in Type 1 Diabetes."

Focusing on type 2 diabetes, Nalinee Poolsup, PhD, from Silpakorn University, Nakhon-Pathom, Thailand, and Naeti Suksomboon, PharmD, PhD and Warisara Jiamsathit, MScPharm, from Mahidol University, Bangkok, Thailand, conclude that SMBG can yield a significant decrease in HbA1C levels in patients with type 2 diabetes when the results of SMBG are used to adjust therapeutic regimens. They describe the benefits of SMBG in "Systematic Review of the Benefits of Self-Monitoring of Blood Glucose on Glycemic Control in Type 2 Diabetes Patients."

In a forward-looking report entitled, "The Future of Self-Monitored Blood Glucose: Mean Blood Glucose Versus Glycosylated Hemoglobin," Roger Mazze, PhD, from the University of Minnesota Medical School, Minneapolis, emphasizes the importance of SMBG in monitoring diurnal glucose patterns, rather than relying solely on HbA1C or mean glucose levels, which can be misleading indicators of therapeutic efficacy.

Posted by dlife at 10:39 AM | Comments (1)

New Vaccine Approach Prevents/Reverses Diabetes in Lab Study at Children's Hospital of Pittsburgh

Results of study are published in Diabetes, a journal of the American Diabetes Association

May 28, 2008 (Eurekalert) - Microspheres carrying targeted nucleic acid molecules fabricated in the laboratory have been shown to prevent and even reverse new-onset cases of type 1 diabetes in animal models. The results of these studies were reported by diabetes researchers at the John G. Rangos Sr. Research Center at Children’s Hospital of Pittsburgh of UPMC and Baxter Healthcare Corporation.

In a research study at Children’s Hospital, the scientists injected the microspheres under the skin near the pancreas of mice with autoimmune diabetes. The microspheres were then captured by white blood cells known as dendritic cells which released the nucleic acid molecules within the dendritic cells. The released molecules reprogrammed these cells, and then migrated to the pancreas. There, they turned off the immune system attack on insulin-producing beta cells. Within weeks, the diabetic mice were producing insulin again with reduced blood glucose levels.

Results of the microsphere study are published in the June issue of Diabetes, the journal of the American Diabetes Association.

In type 1 diabetes, T cells from the immune system travel to the pancreas and destroy beta cells, which produce insulin. The scientists – led by Massimo Trucco, MD, and Nick Giannoukakis, PhD – found that the microspheres reprogram dendritic cells to block the signaling mechanism that sends T cells to destroy beta cells. The microsphere research builds on previous research by Drs. Giannoukakis and Trucco in which they used dendritic cells delivered to the pancreas in another method to turn off the immune system’s attack on insulin-producing beta cells, thereby allowing the cells of the pancreas to recover and begin producing insulin again.

Drs. Trucco and Giannoukakis anticipate that the latest research involving microspheres represents a significant improvement over their previous approach to extract (through a process known as leukapheresis) and reprogram the dendritic cells.

“The microspheres prevented the onset of type 1 diabetes and, most importantly, exhibited a capacity to reverse hyperglycemia, suggesting a potential to reverse type 1 diabetes in new-onset patients,” said Dr. Trucco, chief of the Division of Immunogenetics at Children’s. “This novel microsphere approach represents for the first time a vaccine with the potential to suppress and reverse diabetes. This finding holds true promise for clinical testing in people with type 1 diabetes.”

Currently, Drs. Trucco and Giannoukakis are conducting a clinical trial of their leukapheresis-based dendritic cell approach in humans at Children’s. This Phase 1 clinical trial has been approved by the U.S. Food and Drug Administration (FDA).

“Our ultimate goal is to offer this dendritic cell vaccine or microsphere-based therapy to children at risk for or newly diagnosed with type 1 diabetes. We want to make the procedure as safe and comfortable as possible,” Dr. Giannoukakis said.

The trial began late last year and enrollment is ongoing. The study, which plans to enroll a total of 15 adults over age 18 with type 1 diabetes, is expected to conclude later this year.

If the leukapheresis-based approach continues to show exceptional safety, the researchers hope to launch a national clinical trial that will assess the effectiveness of the dendritic cells in pediatric patients to prevent diabetes or reverse the disease right after it is clinically confirmed. At a later date, it is anticipated that Baxter Healthcare will collaborate with Drs. Trucco and Giannoukakis in a clinical trial utilizing the unique microsphere-based approach.

Leukapheresis is a process that allows for the collection of dendritic cell precursors from the patients in the study, which takes two to four hours. After the precursors are collected, they are treated in the lab with specific growth factors that turn them into dendritic cells. The growth factors are also combined with short DNA sequences that specifically block the expression of molecules that are found at the surface of dendritic cells known as CD40, CD80 and CD86. Once these reprogrammed dendritic cells are tested in the lab, they are injected back into the patient. They then orchestrate an anti-diabetic effect by suppressing the activity of T-cells which are responsible for the impairment and destruction of the pancreatic insulin-producing cells.

“Using microspheres will be much less invasive for the patient and much more efficient for clinicians. We wouldn’t need to harvest a patient’s dendritic cells, and it would eliminate the need to genetically reprogram the dendritic cells in a sterile, off-site facility. Instead, the patient would receive the microsphere injection with a small needle in a clinic setting in a matter of minutes,” Dr. Giannoukakis said.

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The microsphere molecule delivery technology being used is Baxter Healthcare Corporation’s PROMAXX microsphere technology. Larry Brown, ScD, Vice President, Research and Chief Technology Officer and Kimberly Gillis, PhD, Director of Research at Epic Therapeutics (Norwood, MA), part of Baxter’s Medication Delivery business, worked with Drs. Giannoukakis and Trucco to develop the specific diabetes vaccine microspheres. The genetic reprogramming of dendritic cells is an approach developed by Drs. Giannoukakis and Trucco.

Type 1 diabetes is regarded as an autoimmune disease because a person’s immune system’s T cells attack and destroy the beta cells in the pancreas that produce insulin. Symptoms of type 1 diabetes usually develop over a short period of time and include increased thirst, frequent urination, constant hunger, weight loss, blurred vision and extreme fatigue. People with type 1 diabetes require numerous daily injections of insulin to survive. Type 1 diabetes also is known as insulin-dependent diabetes mellitus or juvenile-onset diabetes. The National Institutes of Health (NIH) reports that more than 1 million children and teenagers (age 19 and younger) have type 1 diabetes. According to the NIH, 5 percent to 10 percent of diagnosed diabetes cases in the United States are type 1 diabetes.

Dr. Trucco, an international leader in the field of immunogenetics, has dedicated his life’s work to finding a cure for diabetes. He also is the Hillman Professor of Pediatric Immunology at Children’s Hospital and a professor of Pediatrics at the University of Pittsburgh School of Medicine. His laboratory team at Children’s John G. Rangos Sr. Research Center has pioneered numerous important studies and also maintains a federally funded national bone marrow HLA typing center. For more information about type 1 diabetes or Dr. Trucco’s research, please visit www.chp.edu.

Posted by dlifenews at 01:24 PM | Comments (2)

Study Shows Pine Bark Naturally Reduces Cardiovascular Risk Factors in Diabetics

May 28, 2008 (EurekAlert) - A new study published in the May 2008 (volume 8, issue 25) edition of the journal of Nutrition Research shows Pycnogenol (pic-noj-en-all), an antioxidant plant extract from the bark of the French maritime pine tree, reduces blood sugar in type II diabetes patients, allows people to lower their antihypertensive medication and improves cardiovascular disease (CVD) risk factors. The study, conducted at the University of Arizona, Tucson, indicates Pycnogenol may serve as a potent adjunct to prescription medications for the 20 million people in the Unites States living with diabetes.

“Most people with type II diabetes have cholesterol problems and half of those people experience hypertension. It has been documented that Pycnogenol mediates a number of beneficial effects on the cardiovascular system for diabetics and healthy individuals,” said Dr. Ronald Watson, a lead researcher of the study. “Previous studies have shown Pycnogenol supplementation to be associated with reducing platelet aggregation, lowering LDL and increasing HDL cholesterol and modifying hypertension, among others. But what really makes the study results compelling is Pycnogenol simultaneously lowered blood glucose, LDL cholesterol and blood pressure in patients. Furthermore, this is the first study suggesting that Pycnogenol might also be beneficial in protecting kidney function in diabetics.”

The 12-week, randomized, double-blind, placebo-controlled trial consisted of 48 men and women, 40 to 75 years of age, with noninsulin-dependent type II diabetes, taking anti-diabetic medication with metformin, sulfonylurea and glitazones. Furthermore, they took antihypertensive medications with ACE inhibitors such as Lisinopril. Despite their medication their fasting blood sugar was above healthy values (142 mg/dL) and their average systolic blood pressure was 139 mmHg subjects were randomly assigned to receive either Pycnogenol (25 mg, 5 times daily) or matched placebo. Participants were instructed to continue taking their prescription medications.

Blood pressure and heart rate were recorded at baseline and at biweekly follow-up visits physicians tried to lower the patient’s individual anti-hypertensive medication with aim to keep it below 130 mmHg. At monthly follow-up visits, all unused prescription medications were collected and counted. Change from baseline at weeks four, eight and 12 were calculated after eight hours of fasting for assessing plasma glucose, LDL cholesterol and endothelin-1. Urinary protein concentration was measured from spot urine samples on a monthly basis.

In the Pycnogenol treated groups, results revealed Pycnogenol achieved blood pressure control in 58.3 percent of patients at the end of the 12 weeks with 50 percent reduction in prescription medications. Plasma endothelin-1, a very potent hormone-like arterial constrictor which is typically elevated in diabetes patients, decreased by 17.8 percent. The constriction of arteries is believed to be the cause of hypertension and the decreased endothelin-1 with Pycnogenol is suggested to be the cause for the healthier blood pressure. The mean average blood glucose decreased from high 142.3 mg/dL to a healthy value 118.6, a decrease by 16.7% after 12 weeks. Low-density lipoprotein cholesterol improved significantly, declining by 11.9%.

“It is amazing to see that adding Pycnogenol to the regimen of prescription medication brought blood glucose to healthy levels, allowed half the patients to reach healthy blood pressure and enabled 58% to even lower their anti-hypertensive medication,” said Watson. “An absolutely new finding is that Pycnogenol appears to improve kidney function in diabetic people, this deserves more attention in future investigations. Pycnogenol should be standard adjunct to pharmaceutical treatment of diabetic patients to help control an array of cardiovascular problems.”

In the past four years alone, numerous studies have been published on Pycnogenol’s health benefits for people living with diabetes. In a study published in the March 2004 Diabetes Care, Pycnogenol was shown to lower blood sugar levels and not affect insulin levels. The October 2006 journal of Angiology revealed Pycnogenol reduces diabetic microangiopathy and in 2006, published research in the July journal of Clinical and Applied Thrombosis/Hemostasis revealed Pycnogenol heals leg ulcers in patients who suffer from diabetic leg ulcerations. Additionally, Pycnogenol has been shown to reduce fasting and postprandial serum glucose levels and glycosylated hemoglobin in patients with type II diabetes. And, earlier studies with more than 1,000 diabetes patients, showed that Pycnogenol has the ability to seal leaky capillaries in the eye. This capability stops the progression of vision loss in patients suffering from diabetic retinopathy, a diabetes-induced eye disease that ultimately leads to blindness.

Posted by dlife at 11:25 AM | Comments (50)

New Insights in Diagnosing Diabetes May Help the Millions Who Are Undiagnosed

May 27, 2008 (Newswise) — In light of the 6.2 million Americans who don’t realize they have diabetes, a panel of experts examined the current criteria for screening and diagnosing the disease and found a significant need for improvement. Their conclusions and recommendations can be found in a new report accepted for publication in the Journal of Clinical Endocrinology & Metabolism (JCEM).

“Approximately 30 percent of people with diabetes in the United States are undiagnosed,” said Christopher Saudek, M.D., of Johns Hopkins School of Medicine in Baltimore, Md., and lead author of the report. “There are serious deficiencies in the current criteria for diagnosing diabetes and these shortcomings are contributing to avoidable morbidity and mortality”.

One reason so many people with diabetes are undiagnosed is because commonly prescribed diagnostic tests require that a patient be fasting, said Saudek. This means that people who have eaten on the day of a doctor visit will not be diagnosed unless they have quite advanced diabetes.

As an alternative to the fasting plasma glucose or oral glucose tolerance tests, the panel suggested incorporating another measurement of glucose, hemoglobin A1c (HbA1c), into criteria for screening and diagnosing diabetes.

Hemoglobin is the oxygen-carrying protein located in red blood cells. HbA1c is a form of hemoglobin that reflects the average blood glucose level over the previous several months, and has been used for a long time to indicate blood sugar levels in patients with diabetes. But it has never been officially accepted as a way for doctors to screen for or diagnose diabetes.

Current recommendations of the American Diabetes Association were made a decade ago and they rejected the use of HbA1c as a diagnostic tool largely because it was considered at the time to be inadequately standardized and insensitive. Given more recent evidence, the panel believes it is time to revisit using HbA1c and include it as necessary criteria in screening and diagnosing diabetes.

The measurement of HbA1c does not require fasting, while current accepted tests require the patient to fast for at least eight hours. Furthermore, HbA1c more accurately reflects longer-term glucose concentration in the blood; other tests can easily be affected by short-term lifestyle changes, such as a few days of dieting or exercise. And finally, HbA1c laboratory methods are now well standardized and reliable.

The panel recommends that screening standards be established that prompt further testing and closer follow-up. Standards could include HbA1c tests, for example HbA1c greater than 6 percent would qualify as being in need of follow-up; HbA1c greater than or equal to 6.5 percent confirmed by a glucose-dependent test should establish the diagnosis of diabetes.

Other members of the panel include William Herman of the University of Michigan in Ann Arbor, Mich.; David Sacks of Harvard Medical School in Boston, Mass.; Richard Bergenstal of the International Diabetes Center in Minneapolis, Minn.; David Edelman of Duke University in Durham, N.C.; and Mayer Davidson of Charles R. Drew University in Los Angeles, Calif.

The article “A New Look at Screening and Diagnosing Diabetes Mellitus,” will appear in the July issue of JCEM, a publication of The Endocrine Society.

Posted by dlifenews at 12:51 PM | Comments (1)

Cocoa Could be a Healthy Treat for Diabetic Patients

Flavanols in cocoa improve artery function, help relieve stress on heart

May 26, 2008 (Eurekalert) - For people with diabetes, sipping a mug of steaming, flavorful cocoa may seem a guilty pleasure. But new research suggests that indulging a craving for cocoa can actually help blood vessels to function better and might soon be considered part of a healthy diet for the prevention of cardiovascular disease.

Flavanols, natural plant compounds also found in tea, red wine, and certain fruits and vegetables, are responsible for cocoa’s healthful benefits. In fact, according to new research published in the June 3 issue of the Journal of the American College of Cardiology (JACC), after diabetic patients drank specially formulated high-flavanol cocoa for one month, blood vessel function went from severely impaired to normal.

The improvement was as large as has been observed with exercise and many common diabetic medications, the researchers noted. These findings suggest that it may be time to think not just outside the box, but inside the cup, for innovative ways to ward off cardiovascular disease—the number one cause of death in diabetic patients.

“Medical treatments alone often do not prevent complications of diabetes that are associated with atherosclerosis and cardiovascular disease,” said Malte Kelm, M.D., a professor and chairman of cardiology, pulmonology and vascular medicine at the University Hospital Aachen and the Technical University Aachen, in Aachen, Germany. “Physicians should be increasingly looking to lifestyle changes and new approaches to help in addressing the cardiovascular risks associated with diabetes.”

For the study, Dr. Kelm and his colleagues first tested the feasibility of using high-flavanol cocoa to improve cardiovascular health by observing, on three separate days, the effects of cocoa with varying amounts of flavanols on blood vessel function in 10 patients with stable type 2 diabetes.

The second, larger part of the study tested the effectiveness of long-term, routine consumption of high-flavanol cocoa in comparison with low-flavanol cocoa in 41 patients with stable type 2 diabetes. Patients were randomly assigned to drink cocoa with either 321 mg of flavanols per serving or only 25 mg of flavanols per serving three times daily for 30 days. The two types of cocoa tasted and looked the same, despite differences in flavanol content. In addition, neither patients nor investigators were aware of which type of cocoa each patient had been assigned to drink.

Blood vessel function was tested on the first day before the patients consumed any cocoa and again two hours after drinking the beverage. The test was repeated before and after cocoa consumption on day 8 and day 30.

To gauge the effect of high-flavanol cocoa on blood vessel function, the researchers used a test called “flow-mediated dilation” (FMD), which evaluates the ability of the arteries to expand (dilate) in response to an increase in the demand for blood, oxygen and nutrients. The FMD test involves measuring the diameter of the brachial artery in the upper arm using ultrasound, then inflating a blood pressure cuff on the forearm for several minutes. The squeezing of the blood pressure cuff temporarily starves the forearm muscles of blood and oxygen, causing the body to increase blood flow to those muscles. In healthy people, the inner lining of the arteries, or endothelium, senses the increased blood flow and sends a chemical signal telling the arteries to expand. In Dr. Kelm’s laboratory, a normal FMD response among healthy people the same age as those participating in the study is a 5.2 percent expansion in arterial diameter, on average.

The researchers found that patients with type 2 diabetes had a severely impaired FMD response at the beginning of the study. Before patients consumed any cocoa, the brachial artery expanded by only 3.3 percent, on average. Two hours after drinking high-flavanol cocoa, the FMD response was 4.8 percent.

Over time, those findings improved, however. After patients drank high-flavanol cocoa three times daily for eight days, the average FMD response improved to 4.1 percent at baseline and to 5.7 percent two hours after cocoa ingestion. By day 30, the FMD response had improved to 4.3 percent at baseline and 5.8 percent after cocoa ingestion. All of the improvements were highly statistically significant.

Among patients who consumed low-flavanol cocoa, there were no significant differences in baseline FMD response over time, or in FMD response after cocoa ingestion on days 8 and 30.

FMD measurements can provide valuable information about a person’s cardiovascular health. Previous studies have shown that people with an impaired FMD response have an increased risk of heart attack, need for bypass surgery or catheter procedure to open clogged coronary arteries, and even death from heart disease.

Dr. Kelm speculated that cocoa flavanols improve FMD response by increasing the production of nitric oxide, the chemical signal that tells arteries to relax and widen in response to increased blood flow. Relaxation of the arteries takes stress off of the heart and blood vessels.

The high-flavanol cocoa used in this study—which provided many times more flavanols than the typical U.S. dietary intake of 20 to 100 mg daily—is not sold in the supermarket. Dr. Kelm cautioned that the take-home message of the study is not that people with diabetes should guzzle cocoa, but rather, that dietary flavanols hold promise as a way to prevent heart disease.

“Patients with type 2 diabetes can certainly find ways to fit chocolate into a healthy lifestyle, but this study is not about chocolate, and it’s not about urging those with diabetes to eat more chocolate. This research focuses on what’s at the true heart of the discussion on “healthy chocolate”—it’s about cocoa flavanols, the naturally occurring compounds in cocoa,” he said. “While more research is needed, our results demonstrate that dietary flavanols might have an important impact as part of a healthy diet in the prevention of cardiovascular complications in diabetic patients.”

Umberto Campia, M.D., who co-wrote an editorial about the new study in the same issue of JACC, noted that diabetics are an ideal population in which to study the effects of flavanols on arterial function, because high blood sugar damages the endothelium and because these patients have a high risk of cardiovascular disease.

Any therapy that helps the lining of the arteries to function better is potentially important, said Dr. Campia, a research associate with MedStar Research Institute in Washington, D.C.. “The endothelium is one of the largest organs in the body,” he said. “It maintains the health of the arteries and prevents blockages that can cause heart attacks, strokes and limb loss.”

“This study is important and thought-provoking,” he noted. “We now have sizeable evidence that cocoa flavanols have a positive effect on the health of the arteries. This is the foundation we need for doing a much larger prospective study that looks at the effect of cocoa flavanols not just on endothelial function, but also on the risk of heart attack, stroke, and other serious forms of cardiovascular disease.”

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This study was supported by an unrestricted grant from Mars Inc., McLean, VA. The company also provided the instant cocoa beverage powders used in the study but had no role in the design, conduct, or analysis of the study. One of the authors, Hagen Schroeter, Ph.D., is employed by Symbioscience, a newly established scientific division of Mars, Inc.

The American College of Cardiology is leading the way to optimal cardiovascular care and disease prevention. The College is a 34,000-member nonprofit medical society and bestows the credential Fellow of the American College of Cardiology upon physicians who meet its stringent qualifications. The College is a leader in the formulation of health policy, standards and guidelines, and is a staunch supporter of cardiovascular research. The ACC provides professional education and operates national registries for the measurement and improvement of quality care. More information about the association is available online at www.acc.org.

The American College of Cardiology (ACC) provides these news reports of clinical studies published in the Journal of the American College of Cardiology as a service to physicians, the media, the public and other interested parties. However, statements or opinions expressed in these reports reflect the view of the author(s) and do not represent official policy of the ACC unless stated so.

Posted by dlifenews at 01:02 PM | Comments (25)

Pittsburgh Scientists Find Protein May Be Key to New Therapies For Elevated Triglycerides

High triglycerides common in people who are obese and/or diabetic, at risk for heart disease

May 23, 2008 (Eurekalert) - Diabetes researchers at the John G. Rangos Sr. Research Center at Children’s Hospital of Pittsburgh of UPMC have identified a potential target for the development of new therapies to treat hypertriglyceridemia, a lipid disorder commonly seen in people who are obese and diabetic. Results of their study are published in the June issue of the Journal of Clinical Investigation.

Scientists in the Division of Immunogenetics at Children’s Hospital studied the role of a protein known as Forkhead Box O1 (FoxO1) that mediates the metabolism of glucose and cholesterol. In the laboratory, the researchers were able to curb the secretion of triglycerides in animals that were obese and diabetic by inhibiting the production of FoxO1 in the liver. Elevated triglyceride levels have been identified as a risk factor for heart disease.

“Our latest findings suggest that we may eventually be able to develop drug therapies that inhibit FoxO1, which would thereby inhibit the production of proteins that lead to elevated triglyceride levels in people who are obese and/or who suffer from type 2 diabetes,” said Henry Dong, PhD, a diabetes researcher in the Division of Immunogenetics at Children’s and senior author of the study. “Hypertriglyceridemia is a known risk factor for developing heart disease, the leading cause of death in the United States.”

The research team was led by Dr. Dong, who has been studying the role of FoxO1 for the last seven years. Adama Kamagate, PhD, is the lead author in the study. Dr. Dong is an assistant professor of Pediatrics at the University of Pittsburgh School of Medicine.

Their research suggests that FoxO1 is vital to the regulation of a protein known as microsomal triglyceride transfer protein (MTP). MTP facilitates the production of very low-density lipoproteins (VLDL), which are produced in extreme excess in people with hypertriglyceridemia. The study found that FoxO1 mediates insulin action on the production of MTP in the liver. Augmented production of MTP, caused by the inability of insulin to regulate the activity of FoxO1, led to the overproduction of VLDL and hypertriglyceridemia in mice. Mice that were made to be deficient in FoxO1 in the liver experienced reduced MTP and VLDL production.

Having determined FoxO1’s role in the liver, Children’s researchers now are studying its function in other tissues and organs to determine what an impact such therapies might have on children and adults who are obese and/or have type 2 diabetes, which put a person at risk for heart disease.

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Heart disease is the leading cause of death in the United States and is a major cause of disability, according to the Centers for Disease Control and Prevention. Almost 700,000 people die of heart disease in the United States each year, which is about 29 percent of all U.S. deaths.

For more information about diabetes research at Children’s, visit www.chp.edu.

Posted by dlifenews at 09:53 AM | Comments (0)

Celiac Disease Affects Twice as Many Women

May 22, 2008 (Newswise) — Many people haven’t ever heard of celiac disease, but for the millions of people unable to eat bread, cookies, pizza crust and pasta, it’s a reality they have to live with every day. Celiac disease is an autoimmune digestive disorder that wreaks havoc on the body’s intestines when foods containing gluten are consumed. It affects roughly twice as many women as men. In the United States, it affects two million people or about one in 133 people.

It may seem like an easy condition to manage, but gluten is a protein found in many grains and is in a multitude of foods that include wheat, rye, barley or oats. When foods with gluten are digested, an immune reaction is triggered that damages the surface of the small intestine, resulting in the body’s inability to absorb needed vitamins and nutrients from food.

The other problem is that celiac disease is difficult to diagnose. “In the United States, many cases remain undiagnosed because symptoms vary from person to person and because physicians have not been adequately trained in what to look for,” reports Alessio Fasano, M.D., professor of pediatrics, medicine and physiology at the University of Maryland School of Medicine in Baltimore and director of its Center for Celiac Research, in the center’s newsletter.

Celiac disease can develop at any time in a person’s life. It is more common in Caucasian people and those of European descent. If a family member has the disease, the risk for other members increases, as well. Celiac disease is associated with other autoimmune conditions, including lupus, Type 1 diabetes, rheumatoid arthritis, colitis and thyroid disease.

Although there are no prototypical symptoms of celiac disease, many people with the condition complain of diarrhea, bloating and abdominal pain. One complication of the disease is malabsorption which can present with: weight loss, foul-smelling stools, gas, bloating, weakness and poor growth (in children).

Diagnosing celiac disease is extremely important because strict dietary restriction can prevent serious complications. “A diagnosis means that patients can be advised to eat a gluten-free diet in order to stop the progression of celiac disease. If the chronic symptoms continue, patients are at risk of long-term complications such as anemia, infertility, osteoporosis or even cancer,” Fasano said.

A simple blood test can screen for the disease. Sometimes to confirm the diagnosis, it’s necessary to examine a sample of intestinal tissue to look for damage. Although there is currently no cure for celiac disease, it can be effectively managed by excluding gluten from the diet.

It isn’t an easy task because gluten is found in so many foods, but food labeling has come a long way in the last five years. In 2006, the FDA mandated labels on any products containing wheat, milk, soy, peanuts, shellfish and eggs.

According to the Rochester, Minn., based Mayo Clinic, the FDA is supposed to issue a standard definition of “gluten-free” in August 2008 to facilitate shopping for people with celiac disease. These efforts will help those suffering from the condition and their family members effectively manage important dietary restrictions.

May is National Celiac Disease Awareness Month. The national observance is sponsored by the American Celiac Disease Alliance, which on the World Wide Web at http://www.americanceliac.org. Information on the disease is also available from the Celiac Sprue Association: http://www.csaceliacs.org.

Posted by dlifenews at 05:07 PM | Comments (6)

New Efforts to Help Improve Medical Products for Patient Safety and Quality of Medical Care

May 22, 2008 (HHS.Gov) -- HHS Secretary Mike Leavitt today announced efforts underway at the U.S. Food and Drug Administration (FDA) and the Centers for Medicare & Medicaid Services (CMS) that will complement each other to improve patient safety and the quality of medical care.

“This initiative will tremendously increase the FDA’s capacity to monitor the use of medical products on the market,” Secretary Leavitt said. “We are moving from reactive dependence on voluntary reporting of safety concerns -- to proactive surveillance of medical products on the market. In addition, Medicare data on prescription drug use will be available to help government agencies and academic researchers improve the safety, quality and efficiency of health care services.”

In a white paper released by the FDA today, the agency describes plans for the Sentinel Initiative, which will include the development of a new electronic system that will enable FDA to query a broad array of information to identify possible post-market adverse events. That Sentinel System will be created through public-private partnerships and will capitalize on existing large electronic claims and medical records data sources maintained by private and government entities that agree to participate in this nationwide effort.

A CMS final regulation published today will make it possible for federal agencies, states, and academic researchers to use claims data from the Medicare prescription drug program (Part D) -- subject to protections for beneficiary privacy and commercially sensitive data -- for public health and safety research, quality initiatives, care coordination and other research and analysis.

The Sentinel System is an important example of how electronic health records and other electronic health information, such as the Medicare data, can help move the nation toward a system that delivers safer and better quality health care. President Bush has set the goal of most Americans having access to an interoperable electronic health record by 2014.

FDA’s Proposed Sentinel System Will Strengthen Safety Monitoring of Drugs and Other Medical Products

The new FDA white paper, titled “The Sentinel Initiative -- A National Strategy for Monitoring Medical Product Safety,” describes the proposed Sentinel System and calls for a public-private collaboration to develop and implement it. The report is available at: http://www.fda.gov/oc/initiatives/advance/reports/report0508.html. The system would enable FDA to analyze significantly more information than it can today by tapping into vast databases of health information to detect early signs of emerging safety problems.

“With the Sentinel System we will no longer have to wait years to see how a drug or medical device is affecting millions of people,” said FDA Commissioner Andrew C. von Eschenbach, M.D. “The era of ‘wait and see’ is going to become the era of ‘tell me right now.’ By harnessing the world’s most powerful information technologies, and by partnering with CMS, the VA and DoD, and an array of private health care organizations, we will have the ability to monitor a product’s performance in millions of patients in real time. The Sentinel System will give us an unprecedented ability to detect problems as they first begin to surface.”

Creating an active surveillance system such as the Sentinel System was one of the recommendations made by the Institute of Medicine in a 2006 report on ways to improve the safe use of drugs. The recently passed Food and Drug Administration Amendments Act of 2007 (FDAAA) includes provisions that call for the development of such a system. As planned, the Sentinel System will fulfill some requirements of FDAAA while also meeting additional FDA needs.

Access to CMS Data Will Facilitate Public Health and Safety Research and Quality Initiatives

“We look forward to working with the FDA on the Sentinel Initiative,” said CMS Acting Administrator Kerry Weems. “There’s a clear nexus between the data collected through Medicare’s prescription drug program and the FDA’s role in protecting the public from adverse events. The public health and safety benefits from this cooperative venture with the FDA will be substantial.”

Weems noted that CMS’s most recent survey of beneficiaries indicates that people with Medicare use more than twice as many medications in a year as do other Americans. Medicare beneficiaries use an average of 28 prescriptions in a year, while those who consider themselves in poor health have about 45 prescriptions in a year (source: Medicare current beneficiary survey, 2004). In contrast, other Americans use about 13 prescriptions a year, according to a 2007 study by the Agency for Healthcare Research and Quality (http://www.ahrq.gov/news/nn/nn051607.htm). Medicare beneficiaries’ high usage of medications, coupled with numerous chronic health conditions, puts this population segment at higher risk of adverse drug events than other Americans and makes them the group most likely to see benefits from the FDA’s new Sentinel Initiative.

The Medicare Prescription Drug Benefit data, linked to Medicare inpatient and outpatient claims data, will allow the creation of a highly robust HHS database as the prototype for the Sentinel System. Publication of the Medicare Part D Claims Data Rule enables the FDA to use Part D claims data as the FDA explores drug safety questions related to particular products. Medicare’s Part D prescription drug program, implemented in January 2006, has generated claims data on medications used by the more than 25 million beneficiaries with prescription drug coverage under the benefit. Linking these data on prescription drug use to other Medicare claims information, including diagnoses, medical treatments, hospitalizations, and physician services, will provide the FDA, other agencies, and researchers with a powerful new tool to investigate potential drug safety problems and questions about health outcomes. With approximately 1 billion claims per year, the Medicare Part D database is unprecedented in size and scope and will be a valuable resource for patient safety analyses that will benefit not only Medicare beneficiaries but the entire nation.

Publication of the final rule today will enable CMS to use Medicare Part D claims data for research, program oversight and evaluation, care coordination, quality improvement, and performance measurement initiatives. In compliance with beneficiary privacy protections, as required by the Federal Privacy Act and HIPAA regulations, and while protecting commercially sensitive data, Medicare drug claims will be linked to other Medicare information on patient care, such as hospitalizations and physician visits, and made available to other federal agencies, state Medicaid programs, researchers, and beneficiaries for their personal health records.

CMS will be developing guidelines and workshops to inform researchers on how they can request these data.

The CMS final rule and a related fact sheet may be viewed at www.cms.hhs.gov/PrescriptionDrugCovGenIn/08_PartDData.asp

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High Blood Pressure Patients Advised to Use Home Monitors

May 22, 2008 (American Heart Association) — People with hypertension should routinely monitor their blood pressure at home to help manage the disease, according to a new joint scientific statement from the American Heart Association, American Society of Hypertension and the Preventive Cardiovascular Nurses’ Association.

The statement is published online in Hypertension: Journal of the American Heart Association, the Journal of the American Society of Hypertension and the Journal of Clinical Hypertension and printed in the June issue of Journal of Cardiovascular Nursing.

“High blood pressure is notoriously difficult to treat to goal – many patients fail to reach target levels despite treatment, and studies show home monitoring can help,” said Thomas G. Pickering, M.D., D.Phil., chair of the statement writing group. “Blood pressure measurement and tracking could be improved with home monitoring by the patients themselves, in much the way people with diabetes monitor their blood sugar levels with home glucose monitors.”

He said there is strong evidence that the traditional way of measuring blood pressure in adults can be misleading. Studies indicate that between 10 percent and 20 percent of people diagnosed with high blood pressure in the doctor’s office actually have the ‘white coat effect,’ meaning that their pressures are normal under other conditions, but rise in the medical setting.

“It is also believed that some people with normal blood pressures in their doctors’ offices have pressures that spike to potentially dangerous levels in other situations,” said Pickering, director of the Center for Behavioral Cardiovascular Health at Columbia Presbyterian Medical Center in New York, N.Y.

According to the statement, home monitoring is particularly useful in the elderly, in whom both blood pressure variability and the white coat effect are increased, as well as in patients with diabetes, patients with kidney disease and in pregnant women.

Pickering noted that because everyone’s blood pressure is highly variable during the day, taking one reading at a doctor’s office every few months doesn’t give a complete picture of a person’s condition. Home monitors can take multiple measurements during each session, and can be used at different times of day. Many monitors also store and average blood pressure readings over time, providing crucial data for patients to take to their physicians so they can work as a team to diagnose and treat the condition. Many types of home monitors are relatively inexpensive at less than $100.

“Home blood pressure monitoring also gives patients the physiologic feedback they need to see regarding blood pressure,” says Nancy Houston Miller, R.N., co-author and former president of the Preventive Cardiovascular Nurses Association. “Rather than three to four office blood pressure checks per year, if they measure blood pressure at home in addition to following up with their healthcare provider, patients are likely to achieve goals more quickly and be confident that medicines are working for them.” She also states that nurses and nurse practitioners have a significant role to play in interpreting data from blood pressure devices and educating patients about needed lifestyle interventions and medications.

“We’re encouraged by this joint statement on the value of home blood pressure monitoring and confident it will be helpful in reducing the incidence of heart attack, stroke and kidney disease,” said Suzanne Oparil, M.D., president of the American Society of Hypertension.

Hypertension increases the risk of heart attack and stroke and controlling it is essential to reducing that risk. The statement writing group said home blood pressure monitoring is evidence-based healthcare that can improve the quality and lower the cost of caring for the 73 million people with hypertension.

Although earlier American Heart Association guidelines have included home monitors, this is the first statement to have detailed recommendations on their use.

• Patients should purchase oscillometric monitors with cuffs that fit on the upper arm. They should use a proper fitting cuff, and ask a healthcare provider the proper way to use the monitors.

• Wrist monitors are NOT recommended.

• Patients should take two or three readings at a time, one minute apart, while resting in a seated position. The arm should be supported, with the upper arm at heart level, and feet on the floor (back supported, legs uncrossed). It’s important to take the readings at the same time each day, such as morning and evening, or as a healthcare professional recommends.

• Use of a home monitor can confirm suspected or newly diagnosed hypertension and rule out diagnosis for patients whose readings at the doctor’s office don’t reflect their actual pressures over time.

• Home monitoring can be used to evaluate the response to any type of antihypertensive treatment, and to motivate patients to take their medications regularly.

• The target goal for treatment with a home monitor is less than 135/85 millimeters of mercury (mmHg), or less than 130/80 in high-risk patients.

“I hope this leads to a new era in patient-doctor partnerships,” Pickering said. “I think this is a very healthy trend and with a condition like high blood pressure, it really does depend on the patients remembering to change their lifestyles or remembering to take their pills.”

Only a few of the home blood pressure devices on the market have been subjected to proper validation tests such as the Association for the Advancement of Medical Instrumentation (AAMI) and British Hypertension Society (BHS) protocols. Several devices have failed the tests. An up-to-date list of validated monitors is available on the BHS Web site, http://www.bhsoc.org/default.stm.

Co-authors include Gbenga Ogedegbe, M.D., M.P.H.; Lawrence R. Krakoff, M.D.; Nancy T. Artinian, Ph.D., R.N.; and David Goff, M.D., Ph.D.

The American Heart Association/American Stroke Association receives funding primarily from individuals. In addition, foundations and corporations – including pharmaceutical, device manufacturers and other companies – make donations and fund specific American Heart Association/American Stroke Association programs and events. Revenues from pharmaceutical and device corporations are disclosed at www.americanheart.org.

Posted by dlifenews at 11:35 AM | Comments (0)

Anti-rejection Drug May Increase Risk of Diabetes After Kidney Transplant

May 22, 2008 (Eurekalert) - Washington, DC (Thursday, May 22, 2008) — For patients undergoing kidney transplantation, treatment with the anti-rejection drug sirolimus may lead to an increased risk of diabetes, reports a study in the July Journal of the American Society of Nephrology (JASN).

"We demonstrated a robust association between sirolimus and diabetes after transplantation in a large group of kidney transplant recipients in the United States," comments Dr. John S. Gill of University of British Columbia, Vancouver. "The risk of diabetes was independent of other factors that are known to increase the risk of diabetes."

The researchers analyzed US Renal Data System data on approximately 20,000 Medicare beneficiaries undergoing kidney transplantation between 1995 and 2003. None of the patients had diabetes before their kidney transplant. Treatment with sirolimus was analyzed as a possible contributor to the risk of diabetes developing after transplantation, along with other known and potential risk factors.

"Sirolimus is a newer type of anti-rejection drug that has not been associated with diabetes in transplant recipients," Dr. Gill explains. "However, a number of animal studies and small clinical studies have suggested that sirolimus may increase the risk of diabetes."

The results suggested a higher rate of post-transplant diabetes among patients treated with sirolimus, compared to other anti-rejection drugs. Depending on which additional drugs they received, diabetes risk was 36 to 66 percent higher for patients receiving sirolimus.

Separate analysis of patients who stayed on the same anti-rejection drugs throughout the first year after transplantation showed similar results. The increase in risk was unrelated to any of the other drugs used in combination with sirolimus, or to other risk factors such as age, race/ethnicity, or obesity.

Diabetes is a serious and increasingly common complication occurring after kidney transplantation. "Patients who develop diabetes after transplantation have roughly the same risk of transplant failure as patients who develop acute transplant rejection," says Dr. Gill. Several factors are known to increase the risk of post-transplant diabetes, including some other anti-rejection drugs. The new report is the first large clinical study to suggest that sirolimus may be a risk factor as well.

"Further studies should be done to further clarify the risk of diabetes in sirolimus-treated patients," Dr. Gill adds. He also notes some important limitations of the study, including the fact that it was based on a review of previous data and limited to Medicare patients.

###

The study entitled, “Sirolimus is Associated with New-Onset Diabetes in Kidney Transplant Recipients,” is available online at http://jasn.asnjournals.org/ and will appear in print in the July issue of JASN.

The American Society of Nephrology (ASN) is a not-for-profit organization of 11,000 physicians and scientists dedicated to the study of nephrology and committed to providing a forum for the promulgation of information regarding the latest research and clinical findings on kidney diseases. ASN publishes JASN, the Clinical Journal of the American Society of Nephrology (CJASN), and the Nephrology Self-Assessment Program (NephSAP). In January 2009, ASN will launch a newsmagazine.

Posted by dlifenews at 10:26 AM | Comments (0)

Major 'Missed' Biochemical Pathway Emerges as Important in Virtually All Cells

May 22, 2007 (Eurekalert) - DURHAM, N.C. -- A new study by Duke University researchers provides more evidence that the nitric oxide (NO) system in the life of a cell plays a key role in disease, and the findings point to ways to improve treatment of illnesses such as heart disease and cancer.

The nitric oxide system in cells is “a major biological signaling pathway that has been missed with regard to the way it controls proteins,” and it is linked to cancer and other diseases when the system goes awry, said Jonathan Stamler, M.D., a professor of medicine and biochemistry at Duke University Medical Center who worked on the study.

In the body, nitric oxide plays a role in the transport of oxygen to tissues and physiological activities such as the transmission of nerve impulses, and the beating of the heart. When things go awry with the nitric oxide system, bad things can happen in bodies, according to recent studies. For instance, there may be too little nitric oxide in atherosclerosis and there may be too much in Parkinson’s disease; there may not be enough nitric oxide in sickle cell disease and there may be too much in some types of diabetes, Stamler said.

The new findings, which Stamler said change understanding of how the nitric oxide system is controlled, appear in the May 23 issue of the journal Science.

“What we see now for the first time in the Science paper is that there are enzymes that are removing NO from proteins to control protein activity,” Stamler said. “This action has a broad-based effect, frankly, and probably happens in virtually all cells and across all protein classes. Nitric oxide is implicated in many disease processes. Sepsis, asthma, cystic fibrosis, Parkinson’s disease, heart failure, malignant hyperthermia -- all of these diseases are linked to aberrant nitric-oxide-based signaling.”

An important factor that previously wasn’t appreciated, he said, is that the target of nitric oxide in disease is different in every case. The finding of how nitric oxide binding to proteins is regulated opens the field for new refinement in biochemical research, said Stamler, who has been studying nitric oxide in cells for 15 years.

“Now we will need to study whether the aberrant cell signals are a matter of too much NO being produced and added to proteins or not enough being removed from proteins,” he said. “It is not simply a matter of too much or too little NO being in cells, but rather how much is being added or taken away from specific proteins, which is quite a different thing.”

First author on the paper, Moran Benhar, Ph.D., and co-author Douglas Hess, Ph.D., are both in the Duke Department of Medicine. Co-author Michael Forrester is a graduate student in the Duke Department of Biochemistry.

The research explains that the enzymes thioredoxin 1 and thioredoxin 2 remove nitric oxide from the amino acid cysteine within mammalian cells, thereby regulating several different actions in cells. One result of this removal is the activation of molecules that begin apoptosis, which is the normal programmed death of a cell. This process has potential importance for many diseases, including inflammatory diseases, heart failure and cancer. Because thioredoxins are established targets of drug therapy for arthritis, the research suggests potential therapeutic applications of the process.

The nitric oxide system is analogous to the much more studied phosphorylation system, in which phosphates are added and removed from proteins, the paper said. Changes in phosphorylation are among the most common causes of disease, and proteins that regulate phosphorylation are major drug targets, Stamler said.

“Aberrant dephosphosphorylation causes disease. Expect the same for denitrosylation,” Stamler said.

Similar research at Duke that was published in the journal Nature on March 16 supports Stamler’s findings. Christopher Counter, an associate professor in the Duke Department of Pharmacology and Cancer Biology, and colleagues found that eNOS (endothelial nitric oxide synthase), an enzyme that enhances the creation of nitric oxide, promoted tumor development and tumor maintenance in mice.

“The Chris Counter work is especially exciting because he shows that a nitric oxide synthase is linked to cancer, and he specifically identifies the protein that is the target of the nitric oxide, the protein that gets turned on through S-nitrosylation,” Stamler said. Blocking S-nitrosylation of this protein prevented cancer.

The steady stream of new papers on nitric oxide seems to underscore Stamler’s long-held belief that nitric oxide affects cells in bigger ways than many had appreciated. “When we began our studies two decades ago, we hypothesized that nitric oxide was part of a significant, broad-based system,” Stamler said. “Our hypothesis never changed.”

Posted by dlifenews at 10:17 AM | Comments (0)

Combined Kidney-Pancreas Transplant Improves Survival in Type 1 Diabetes

May 21, 2008 (Newswise) - For patients with type 1 diabetes and end-stage renal disease (ESRD), simultaneous kidney-pancreas transplantation increases the chances of long-term survival compared to kidney transplantation alone, reports a study in the August 2008 issue of Journal of the American Society of Nephrology (JASN).

"Based on these results, we feel that all type 1 diabetics with kidney failure should be considered for simultaneous pancreas-kidney transplantation," comments Dr. Christian Morath of the University of Heidelberg, Germany.

Dr. Morath and colleagues analyzed the long-term outcomes of more than 11,000 patients with type 1 diabetes and ESRD who received a kidney transplant between 1984 and 2000. About 3,500 patients underwent simultaneous transplantation of the pancreas and kidney from a deceased donor. The remaining patients received a kidney only, from either a living or deceased donor.

Patient survival and survival of the transplanted kidney were evaluated after up to 18 years of follow-up. The goal was to see how adding pancreas transplantation to kidney transplantation affected the long-term outcomes.

Both patient and kidney survival were better for patients undergoing pancreas-kidney transplant or living-donor kidney transplant, compared to deceased-donor kidney transplant. At first, kidney survival rates were best for patients who received living-donor kidney transplants. However, by the end of the follow-up period, kidney survival rates were essentially the same for the pancreas-kidney and living-donor kidney groups.

When adjusted for other factors, patients receiving simultaneous pancreas-kidney transplants had better long-term survival. Beyond 10 years, the risk of death was 45 percent lower in the pancreas-kidney group than in the living-donor kidney group. The gain in survival with pancreas-kidney transplantation largely reflected a lower risk of death from cardiovascular disease: 37 percent, compared with 46 to 49 percent in patients receiving kidney transplants only.

For all groups, survival rates were better for patients transplanted after 1990. This finding reflected advances in transplantation surgery and anti-rejection therapy.

ESRD is a major complication of type 1 diabetes, previously called "juvenile" or "insulin-dependent" diabetes. Over the past two decades, combined pancreas-kidney transplantation has emerged as a treatment alternative for type 1 diabetics with ESRD. If successful, the pancreas transplant "cures" the diabetes—patients usually no longer need to take insulin (although they must take medications to prevent rejection of the transplanted organs).

"Our study shows that a functioning pancreas has a benefit for the simultaneously transplanted kidney," says Dr. Morath. "At the same time, this procedure prolongs the survival of the patient, compared to a patient who received only a kidney transplant."

The improvement in survival appears to result from a lower rate of cardiovascular deaths in patients undergoing pancreas-kidney transplantation. "The reduced cardiovascular mortality is most likely due to the normoglycemia [normal blood sugar levels] in patients who received a combined transplant," adds Dr. Morath. "The results show an interaction of different and independent organs—kidney, pancreas, and heart—with respect to survival of the patient."

Given the long-term improvement in survival, combined pancreas-kidney transplantation should be considered in every patient with type 1 diabetes and ESRD. Dr. Morath and colleagues believe. "In addition, research should focus on methods which are able to normalize blood glucose [sugar] levels in type 1 diabetic patients, such as islet cell transplantation."

The study entitled, "Metabolic Control Improves Long-Term Renal Allograft and Patient Survival in Type 1 Diabetes," will be available online at http://jasn.asnjournals.org/ beginning on Wednesday, May 21, 2008, and in print in the August issue of JASN.

The American Society of Nephrology (ASN) is a not-for-profit organization of 11,000 physicians and scientists dedicated to the study of nephrology and committed to providing a forum for the promulgation of information regarding the latest research and clinical findings on kidney diseases. ASN publishes JASN, the Clinical Journal of the American Society of Nephrology (CJASN), and the Nephrology Self-Assessment Program (NephSAP). In January 2009, ASN will launch a newsmagazine.

Posted by dlifenews at 03:16 PM | Comments (0)

Anti-inflammatory Medication May Treat Type 2 Diabetes

May 21, 2008 (Newswise) — Researchers at the Joslin Diabetes Center who reported earlier this year that an inexpensive, non-steroidal anti-inflammatory drug called salsalate might prevent type 2 diabetes are now reporting that the drug may also be beneficial in the treatment of the disease.

The paper, which appears in the May 2008 issue of the journal Clinical and Translational Science (CTS), reports on three proof-of-concept studies that demonstrate that salsalate, which has been used for decades to treat arthritis, may benefit patients with type 2 diabetes by lowering blood sugar and reducing inflammation.

“These are the first studies showing that potentially safe and tolerable doses of salsalate lower blood sugars and have other favorable effects in patients with type 2 diabetes,” notes Allison B. Goldfine, M.D., Director of Clinical Research at Joslin and Associate Professor at Harvard Medical School, and senior author of the report.

Goldfine was also the lead researcher for an earlier study, published in the February issue of Diabetes Care, which demonstrated that salsalate may prevent type 2 diabetes by lowering blood glucose and reducing inflammation.

Together, these four proof-of-concept studies have led to three large, ongoing multi-center clinical trials that seek to confirm the benefit of targeting inflammation using salsalate to lower glucose in patients with type 2 diabetes or who are at risk for diabetes, or to reduce atherosclerosis in patients with coronary artery disease.

The clinical studies are a direct extension of the findings of study co-author and collaborator Steven Shoelson, M.D., Ph.D., Helen and Morton Adler Chair, Head of the Section of Cellular and Molecular Physiology at Joslin, and Professor at Harvard Medical School. Dr. Shoelson studies the molecular pathogenesis of type 2 diabetes and the role of obesity in promoting diabetes and other metabolic conditions, including atherosclerosis.

It had originally been noted nearly 150 years ago that salicylates could lower blood glucose levels, but this had either been forgotten or ignored. Dr. Shoelson’s laboratory used this as clue to probe potential reasons why obesity promotes disease. They found that the inflammatory pathway regulated by NF-kB is activated in animals with obesity and diabetes. They went on to demonstrate that this pathway could be inhibited using salicylates, thus showing that the effects of obesity are mediated through inflammation. This was not an accepted concept at the time, and is still debated in field.

Studies in animals showed that high doses of salicylates, including aspirin, could be effective, but since these could not be used safely in patients due to the risk of stomach upset and bleeding the researchers considered alternative drugs. Together, Drs. Goldfine and Shoelson opted to study salsalate, which is a salicylate similar to aspirin but that does not cause stomach upset or bleeding.

Shoelson notes that the studies now being reported in CTS provide a ‘smoking gun’ – new evidence that incriminates inflammation as a major pathogenic mediator in type 2 diabetes – as well as a potentially safe new way to treat the disease.

“It is rare to see basic discoveries move from bench to bedside so quickly. This was fueled by at least two things, first the ready availability of a safe drug, and second the environment at the Joslin Diabetes Center which is ideally suited to rapid advancements in clinical discovery,” he said.

Goldfine further opines, “much of the pharmacokinetic and long-term safety data for salsalate is already established, so clinical studies could move forward rapidly.”

“Our findings are potentially very exciting because we show that a medication that treats inflammation may also treat diabetes and related medical conditions,” said Goldfine. “If we can show in the larger clinical trials now underway that it is safe and effective, it means salsalate may be a new way to treat diabetes.”

In the paper out today, two of the studies involved small numbers of patients with type 2 diabetes. One tested salsalate on seven subjects at a dose of 4.5 grams per day, while the other used 3 grams per day on nine subjects. Patients in both groups showed benefits such as reductions in blood sugar between 10 and 20 percent, but improvements were greatest in the group taking the higher dose. Glucose utilization also improved in both groups, although those taking the higher dose showed a 50 percent improvement, compared to 15 percent for those on the lower dose. The studies ran for two weeks each.

Impressive reductions were also seen in circulating levels of triglycerides and free fatty acids, particularly at the higher dose. This is important because patients with diabetes often have elevated lipid levels that potentially contribute to complications of type 2 diabetes.

The third study, a double blind, placebo-controlled trial that ran for four weeks, involved eight patients on the drug and nine on placebo. Study participants on the drug showed improvements similar to those reported in the patients in the other two studies analyzed.

In an accompanying commentary, Barry J. Goldstein, M.D., of the Division of Endocrinology, Diabetes and Metabolic Diseases, Jefferson Medical College, wrote: “The testing of a commonly used class of drugs, with a well-known safety profile, offers an exciting translational approach that promises to help in the management of glycemia in type 2 diabetes.”

He noted: “A world-wide epidemic of type 2 diabetes is underway that shows no signs of remitting in the next several years. In order to address the basic therapeutic needs of these millions of patients, additional treatment options will need to be made available, especially to have some hope of getting the majority of patients to accepted glucose treatment goals.”

The studies were funded by grants from the National Institutes of Health; fellowships from the William Randolph Hearst Foundation and American Diabetes Association; and the Helen and Morton Adler Chair at Joslin Diabetes Center.

Other researchers participating included Robert Silver, Elizabeth Tatro and Jongsoon Lee at Joslin; Waleed Aldahi of Mubarik Alkabeer University Hospital, Kuwait; and Dongsheng Cai of the University of Wisconsin.

Salsalate Clinical Trials
Dr. Goldfine is the principal investigator of a study that targets inflammation using salsalate in patients with coronary artery disease and metabolic syndrome. The study, called Targeting INflammation using SALsalate or Lifestyle intervention in the Metabolic Syndrome and Cardiovascular Disease (TINSAL-CVD), is funded by The National Heart, Lung and Blood Institute and is currently enrolling patients. It will look at the effects of lifestyle intervention (diet, exercise and omega-3 fatty acid supplement) or salsalate compared to placebo to reduce progression or promote regression of hard and soft coronary artery calcification as assessed by multi-detector CT angiography (MDCTA), a relatively new method to image the coronary arteries. Patients are randomized to lifestyle, salsalate or placebo with images of the coronary arteries at baseline and after 30 months of intervention. Dr. Shoelson is co-PI on the salsalate arm of the trial, while study collaborators Dr. Ernest Schaefer of The Jean Mayer USDA Human Nutrition Center on Aging at Tufts University and Dr. Francine Welty of Beth Israel Deaconess Medical Center (BIDMC) are running the lifestyle intervention arm; Dr. Melvin Clouse of BIDMC is leading the imaging core.

A second study called Targeting Inflammation using SALsalate in Type 2 Diabetes (TINSAL-T2D) headed by Drs. Goldfine and Shoelson is using salsalate in patients with type 2 diabetes to target inflammation and thus lower blood glucose. This study is ongoing and is funded by the National Institute of Diabetes and Digestive and Kidney Diseases.

Another study led by Dr. Goldfine and Dr. Peter Reaven of the Carl T. Hayden VA Medical Center in Phoenix targets inflammation using salsalate in patients with impaired glucose tolerance in order to improve insulin sensitivity. This study, called TINSAL-IGT, is ongoing and is funded by the VA.

Posted by dlifenews at 08:29 AM | Comments (2)

New Research Improves Early Detection and Survival for Pancreatic Cancer

May 20, 2008 (Eurekalert) – New research will be presented today at Digestive Disease Week® 2008 (DDW®) to showcase innovative methods to better understand the risk factors for and improve earlier detection of pancreatic cancer. Specifically, researchers will demonstrate that the development of, new biomarkers, novel treatment targets, innovative approaches to screening and surveillance and improved understanding of risk factors can lead to diagnosis of pancreatic cancer at earlier more treatable stages. DDW is the largest international gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

“Pancreatic cancer is the fourth-leading cause of cancer death in the U.S., taking 34,000 lives every year,“ said Mark P. Callery, MD, MACS, associate professor of surgery, Harvard Medical School, chief, division of general surgery Beth Israel Deaconess Medical Center. “It’s vitally important that we make pancreatic cancer a research priority. Signs and symptoms of the disease may not present themselves until advanced stages, when surgical removal of the cancer is no longer possible. This year at DDW, advances in pancreatic cancer research are front and center, providing hope for those who suffer or may suffer from this disease.”

The five-year survival rate for pancreatic cancer is only four percent, but if detected at Stage 1, the survival rate can be as high as 33 percent.

Endosonographic Evaluation Improves Survival in Patients with Pancreatic Cancer (Abstract #762)

Due to a lack of early detection and treatment options, pancreatic cancer is deadly. In fact, a vast majority of patients with pancreatic cancer die because the disease has spread so far that it can no longer be removed. However, a small percentage of pancreatic cancers are caught early enough for a curative surgery to allow removal of the tumor, which may result in improved survival.

Researchers are fervently searching for new, improved technologies that could either detect pancreatic cancer earlier or treat it once it’s detected. Endoscopic ultrasound (EUS) is an expensive treatment, but shows great promise in helping to improve patient outcomes after a diagnosis with pancreatic cancer. Researchers for this study sought to learn about the association between EUS performance and pancreatic cancer survival. To achieve this, investigators reviewed the SEER-Medicare database of patients receiving treatment between January 1994 and December 2002. In all, the records of 4,236 patients with pancreatic cancer were assessed, and broken into two groups – those who received EUS (only 12 percent of the sample) and those who did not (88 percent).

Researchers found that after they controlled for age, race, gender and comorbidities, those who did receive EUS at the time of diagnosis had a longer average survival time (nine months) than those who did not receive EUS (five months).

“Good initial investigation by EUS makes a significant difference for patients with pancreatic cancer,” said Ananya Das, MD, associate chair of medicine, Mayo Clinic, Scottsdale, Arizona. “Though the treatment is expensive and not available everywhere, it has shown to be a marker for better care and treatment planning.”

Dose Dependent Effects of Alcohol and Tobacco on Age of Presentation in Pancreatic Cancer (PC): A Multi-Center, International Study (Abstract # W1401)

Smoking tobacco and drinking alcohol have an effect on the age at which a patients present with pancreatic cancer. This multi-center, international study shows that among patients with pancreatic cancer, heavy smokers and drinkers show the youngest onset. While the average age for the onset of pancreatic cancer is in the 70 to 80 year age range, smokers and drinkers show onset as early as in their 50s, and the more tobacco and alcohol consumed, the earlier the onset.

A previous study using insurance data showed that tobacco and alcohol use affected the age of onset of pancreatic cancer but the effect of the amount and length of time of its use was unknown.

This study, using The Pancreatic Cancer Collaborative Registry, a multi-center international patient registry, captured data for the first time on the dose amounts of tobacco and alcohol used by pancreatic cancer patients along with data on the type of alcohol consumed. The registry was queried for patient age at diagnosis, gender, race, diabetic status, family history of pancreatic cancer, and tobacco and alcohol use.

“We found that the more smoking and drinking done by the patient, the younger the onset of the cancer, and that of the two, drinking has a worse effect,” said Michelle A. Anderson, MD, assistant professor of medicine at the University of Michigan. Heavy drinkers (more than three drinks a day) presented with pancreatic cancer 10 years younger than those who did not drink, while heavy smokers* presented seven years younger than those who did not smoke.

Among the different types of alcohol studied (beer, wine and hard liquor), beer was the strongest in lowering the age of presentation. The median age of onset for those who drank only beer was 62.2 years compared with 68.2 years for those consuming other types of alcohol. “This study strengthens the validity of the data showing that these toxins may be important in the pathogenesis of pancreatic cancer,” said Dr. Anderson.

Researchers did not find a synergistic relationship between the use of tobacco and alcohol, meaning that the age of onset was not profoundly worse if the patient used both, although the size of the study may have affected this finding.

Other limitations of the study include the fact that patients were being asked to recall their past use of tobacco and alcohol and a potential for selection bias. Also, because all of the centers using the registry are academic medical centers, the type of patient may be different than the type of patient who would go elsewhere for care.

A heavy smoker is a person with a pack value > 40. Pack values were determined by multiplying the number of years a person has smoked by the pack per day they smoke (e.g. a person who smokes a pack per day for 20 years has a pack value of 20 while a person who smokes half a pack per day for 20 years has a pack value of 10).

Surveillance and Natural History of High Risk Patients who Inherit Pancreatic Cancer (Abstract #644)

In patients who are at very high risk of inheriting pancreatic cancer, surveillance can be effective if performed by a team of experienced specialists. The findings are important because at least 10 percent of pancreatic cancer is inherited and it is a lethal disease that is often not detected until it is too late, since the pancreas is not easily sampled, looked at or felt.

“For these reasons, detecting abnormalities at the pre-cancerous stage has great potential to save lives,” said Teresa A. Brentnall, MD, associate professor of medicine at the division of gastroenterology at the University of Washington, Seattle.

Investigators studied 100 patients for 10 years in a specialized program. The patients were selected from two groups: patients with two or more family members with pancreatic cancer, at least one of whom was a first-degree relative; and patients with a known gene for a lifetime risk of pancreatic cancer of 15 percent or more.

Patients were examined using endoscopic ultrasound (EUS), a combined procedure using endoscopy and ultrasound to obtain information and images about the digestive tract, as well as surrounding organs and tissue. EUS can show whether the pancreas appears to be unhealthy, but it doesn’t show exactly what the problem may be or how severe it may be.

Patients whose EUS detected problems were given a choice: either do nothing and let the cancer form – a risky option, since cells can go from normal to cancerous in one year – or remove the pancreas, which causes diabetes. “The stakes are very high. The pancreatic cancer survival rate is only about five years. There is also the risk that the patient could suffer complications from diabetes which could be fatal,” said Dr. Brentnall.

Of the 100 patients, 52 had an abnormal EUS on initial exam; three of them abstained from alcohol and their status returned to normal. Also, 10 of the 48 who initially had a normal EUS developed new abnormal EUS changes under surveillance. Two patients who went on to have cancer developed new masses at one and four years after surveillance; the masses developed within one year of an abnormal EUS with no masses. Finally, none of the patients with advanced pancreatic pre-cancer who had surgery developed pancreatic cancer during an average follow-up of seven years.

The majority of patients in the study did not opt for surgery and instead were monitored as part of a rigorous surveillance program in which their progress was closely tracked. Physicians worked closely with patients to determine their prognosis and make tailored recommendations. “EUS can assist in the detection of pancreatic neoplasia when performed in a specialized center and can lead to the detection of curable pancreatic pre-cancer,” said Dr. Brentnall.

She added that the program can only exist successfully with a staff that is specifically designated as part of a surveillance team, and that the endoscopic training – and practice – is rigorous, so many hospitals in different areas of the country would not be likely to have such a program. Another difficulty is that experts tend to disagree on what EUS reveals; images tend to be more suggestive and less definitive, which also complicates detection and therefore treatment.

Pancreatic Cancer Screening in a High-Risk Population: Preliminary Data of a Multi-Center Trial Employing Carbohydrate Antigen (CA) 19-9 and Endoscopic Ultrasound (Abstract #M1431)

A new screening method using CA19-9, a tumor marker that is most often used to monitor disease progress as well as predict survival rates, with endoscopic ultrasound is more likely to detect pancreatic cancer in its early stages when it is most treatable. The finding is significant because a nationally-accepted screening tool for pancreatic cancer does not exist. Currently, most cases are detected when patients present with symptoms at advanced stages of the disease.

“Pancreatic cancer is more detectable through this process than traditional screening protocols,” said Richard Zubarik, MD, associate professor of medicine and chief of endoscopy at Fletcher Allen Health Care, Burlington, Vermont. “Our research finds that the CA 19-9 screening method can detect pancreatic cancer at an earlier stage in high-risk populations.” These include people with a first degree relative with pancreatic cancer, people who smoke, people with diabetes, and people aged 50 or older. Dr. Zubarik added that more than 90 percent of the people who develop pancreatic cancer are over the age of 50.

For the study, investigators performed an endoscopic ultrasound if the CA 19-9 level was =37 (reference range 0 – 37 U/ml). Fine needle aspiration was performed during this process if a lesion was identified. Patients with pancreatic cancer detected through this protocol were compared to patients who were not screened through this method.

Medicare reimbursement rates were used to determine cost data, and investigators concluded that the new screening method is expected to reduce medical costs. The cost to detect pancreatic cancer was just over $14,000, and the cost to detect pancreatic neoplastic tumors (abnormal cell growth) using this method is approximately $11,000.

The new screening method does have limitations. With very small tumors, its sensitivity declines. Still, Stage 1 cancers are significantly more likely to be detected through this protocol than through more traditional methods. “Right now, this appears to be the best test we have. We hope this will help us develop even better screening tools in the future,” Dr. Zubarik said.

Development of Monoclonal Antibodies to Aid in the Diagnosis of Pancreatic Cancer (Abstract #1838)

Investigators have developed antibodies that recognize pancreatic cancer. The antibodies were developed through a technique of injecting normal pancreas cells into mice.

Early detection and treatment of pancreatic cancer is critical; the best available treatment for pancreatic cancer is surgery, which is only effective at early stages of the disease. But less than 15 percent of patients are diagnosed with pancreatic cancer at an early stage.

Investigators developed the Oregon Pancreas Tumor Registry, which serves two functions: first, it is intended to keep patients at high risk for pancreatic cancer under surveillance, with the goal of early diagnosis. Also, it acts as a biospecimen repository in which patients and families may provide blood, pancreatic ductal fluid and tissue samples. Doctors may then use the samples for pancreatic cancer research, according to Brett C. Sheppard, MD,Professor and Vice-Chairman of Surgery at the Digestive Health Center at the Oregon Health Sciences University (OHSU).

For this study, OHSU researchers in the Oregon Stem Cell Center and in the Department of General Surgery generated and characterized antibodies. These antibodies were developed following the injection of normal pancreas cells into mice. They next took the spleen cells of the mice and fused them with a myeloma cell line, which yields cells that can be grown for long periods of time in the laboratory. These cells secreted antibodies which researchers were then able to screen for reaction with normal pancreatic and pancreatic cancer tissues.

“The antibodies described in this abstract, recognize normal pancreas cells, specifically a population of ductal cells, but recognize many more cells in pancreatic cancer tissue. In addition to recognizing pancreatic cancer, these antibodies recognize gastrointestinal cancers. The next step is to use these antibodies in a sensitive screening assay to determine their full potential in diagnosis of this devastating disease.“

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Glycemic Stability May Be Important Key to Recovery from Critical Illness

May 20, 2008 (Eurekalert)—Widely varying blood glucose levels may pose as great a threat, or possibly a greater threat, to critically ill patients as high, but steady, glycemic levels, according to researchers in Saudi Arabia, who will present their findings at the American Thoracic Society’s 2008 International Conference in Toronto on Tuesday, May 20.

“We found that patients with wide fluctuation were significantly more likely to die in the intensive care unit and the hospital than those who experience low glycemic variability,” said Hasan M. Al-Dorzi, M.D., who led the research at King AdbulAziz Medical City, in Riyadh. “This finding may lead to further research that changes our focus from only treating high blood glucose to also minimizing changes in glycemic levels.”

Other studies have shown that glycemic variability increases diabetic complications. This study is one of the first to evaluate glycemic variability and the outcomes of critically ill patients.

To conduct the study, the researchers evaluated a nested cohort of 523 patients who were prospectively randomized to either intensive or conventional insulin therapy. After evaluating the daily blood glucose range of all the patients and determining a median, the patients were divided into two groups: those with high variability of blood glucose levels and those with low variability.

Patients in the high variability group were 12 percent more likely to die. They were also more likely to develop a nosocomial infection while in the hospital.

The study identified three predictors of glycemic variability: age, previous diabetes history and whether the patient’s diabetes was controlled with insulin.

Dr. Al-Dorzi suggested that future research could result in improved care for these patients by establishing a standard definition of high variability and developing ways for minimizing blood glucose changes. The latter, he explained, might require an “automated, continuous blood glucose measurement system with computerized insulin protocols.”

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Study: Doctors Not Always Sure When to Treat BP in People with Diabetes

Even when pressure is high, uncertainty stems from ambiguous standards, competing demands and overlapping health problems, U-M/VA study finds

May 19, 2008 (UMHS Newsroom) – For people with diabetes, high blood pressure poses a special threat, multiplying their risk of heart attacks, strokes and kidney problems.

But a new study finds that even when people with diabetes show up in their doctor’s office with a high blood pressure reading, there’s only a 50-50 chance that each of them will get some sort of attention for it. That might mean a change to their medications, or a plan to follow up a few weeks later to see if the reading is still high.

What happens the other 50 percent of the time? Something that others have termed “clinical inertia” takes over, say the University of Michigan Health System and VA Ann Arbor Healthcare System researchers who conducted the study, which is appearing in the May 20 issue of the Annals of Internal Medicine.

The fear is that this lack of response to high blood pressure readings at clinic visits could mean that patients’ pressures will keep getting worse.

The study takes a look at possible causes of clinical inertia and finds little evidence supporting the idea that providers are just “ignoring” blood pressure problems.

What really seems to have an impact on treatment decisions is plain old uncertainty about whether the blood pressure is really elevated, or providers being occupied with other medical issues. Providers might need to spend the visit addressing more pressing problems, some of which, like pain, may be contributing to elevated blood pressures. Or, they might take another reading and conclude there’s no need for action. Or, patients may report that their pressure readings at home have been fine.

More systematic guidelines for monitoring blood pressure in people with diabetes, and better guidance for when to change treatment when pressures get too high, are needed, say the researchers. They’re led by Eve Kerr, M.D., MPH, and Timothy Hofer, M.D., M.S., of the Center for Clinical Management Research at the VA Ann Arbor Healthcare System and U-M Medical School’s Division of General Medicine.

In the meantime, says Kerr, “While there are many guidelines about treating hypertension, there is an amazing lack of clarity and guidance about how many blood pressures should be taken at a clinic visit, whether those blood pressures should be averaged or whether just the lowest should be used, and how to incorporate home blood pressure readings in decisions to intensify medications. As long as this confusion exists, we may not make progress in treating hypertension.”

The study was performed among 1,169 people with diabetes who were seen in VA primary care clinics over a one-year period, at nine different sites in three states.

All the patients had a blood pressure reading over 140/90 mm Hg at the start of their clinic visits. The national goal for people with diabetes is less than 130/80 mm Hg. (For people without diabetes or kidney problems, the goal is less than 140/90, which is considered the cutoff for Stage I hypertension.)

Of these patients, 573, or 49 percent, received a change in their blood pressure treatment at the same clinic visit – either a new prescription for a medication, a change in the dosage of an existing medication or medications, or a documented plan to follow up within four weeks. While this rate is higher than has been reported in other settings, there still appears to be room for improvement.

As part of the study, the researchers asked both patients and providers to complete brief questionnaires before the end of the day of the clinic visit. Most of the 92 providers who saw the patients were physicians, but they also included nurse practitioners and physician assistants. This prospective design allowed the researchers to look at all the different variables associated with providers’ tendency to adjust blood pressure treatment in reaction to the high initial reading.

Their analysis revealed findings that have implications for how patients, and clinicians, measure and react to blood pressure in clinics. For instance, there was wide variation among clinics in the likelihood that providers would order a treatment change in patients with a reading over 140/90 mm Hg.

Uncertainty about what the patient’s blood pressure was one of the largest factors. Providers variably repeated the blood pressure check once the patient was in the exam room, and not surprisingly were much less likely to change treatment if the new reading was lower than 140/90 mm Hg. Only 13 percent of such patients had a treatment change, compared with 61 percent of those with a high second reading, or who didn’t get one.

“Providers clearly ‘trust’ their own reading more than they do the reading taken at the clinic intake point,” suggests Hofer. “But there is no evidence that supports that approach. In fact, the literature suggests that provider measurements are less reliable and subject to large biases relative to independent measures by nurses using electronic blood pressure cuffs.”

Additionally providers responded to their patient’s own report about what kind of readings he or she was getting using a home blood pressure monitor. Only 18 percent of patients who told their providers their home measurements had been below 140/90 mm Hg received a treatment change, compared with 52 percent who said their pressures at home had been high, or who didn’t report at-home monitoring.

While at-home monitoring can be important, Kerr says, the fact of the matter is that there is no standard for how often to monitor and how to record home pressure readings over time. Further, patients might preferentially report only the “normal” blood pressures and ignore the out-of-range values.

Patients should talk to their doctors about how often to monitor and record their blood pressure and look at averages over time, she says. If their average is above the target, it might be time to change treatment.

Finally, another major factor interfering with a patient’s chances of getting a treatment adjustment turned out to be somewhat predictable: attention to other issues. If a patient’s chief reason for coming to the clinic was unrelated to their diabetes or their blood pressure – for instance, if they were seeking treatment for pain – they were much less likely to receive attention for their blood pressure. The same was true for clinic visits where a patient’s medications weren’t discussed.

The team is continuing its study to see how long it takes for patients to get a treatment change. They hope their work will help guide further hypertension guidelines, and standardization of clinic practices. And that, they hope, will help millions of diabetes patients protect their long-term health.

In addition to Kerr and Hofer, the researchers include Brian Zikmund-Fisher, Ph.D., Mandi Klamerus, MPH, Usha Subramanian, M.D., M.S., and Mary M. Hogan, Ph.D., RN. Funding for the study came from the VA, and from the Michigan Diabetes Research and Training Center.

Reference: Annals of Internal Medicine, May 20, 2008, Vol. 148, No. 10.

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