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DATE: December 29, 2006

It has long been suspected that a high sugar diet over a long term period may lead to an increased risk of developing diabetes. But there has been little or no evidence to support this idea, with studies on the role of any aspect of the diet in the development of diabetes difficult to conduct.

Researchers from the Royal Victoria Hospital at Queens University Belfast Ireland have just published the results of a clinical trial looking at the effects of high sugar intake on insulin resistance (said to be a precursor of Type 2 diabetes) and vascular health in 13 healthy non-diabetic men. Sharing their findings in this months Diabetes journal, Dr Steven Hunter and his team of researchers report that those who received 25% of their calorie intake from sucrose (sugar) as part of a balanced, weight maintaining diet for 6 weeks showed no difference in their degree of insulin resistance, compared to a eucaloric (calorie matched) diet providing 10% of energy as sucrose (control).

In this study, the 25% treatment diet provided on average 200g sucrose per day compared with 80g sucrose from the control (10%) diet (around the average for a British adult).

Dr Hunter of the Royal Victoria Hospital said: Sugar has traditionally been linked to the development of diabetes. These findings challenge that thinking, and show that intakes of more than double that currently recommended do not appear to have an adverse effect on markers of diabetes risk.ť

The study saw 13 healthy men receive either a high-sugar diet (providing 25% of their energy) or a diet providing 10% of their energy as sugar for a period of 6 weeks. After the 6 weeks, subjects crossed over to receive the other treatment for a further 6 weeks. Treatments were separated by a four week wash out period, during which the subjects returned to their usual diet.

The diets for each period were closely matched in overall macro nutrient (carbohydrate, fat and protein) composition. The only difference was in substituting sucrose (sugar) for starch. Insulin resistance was measured by the research gold standard, a two-step glucose clamp.

Furthermore, the high sucrose diet showed no significant adverse effects on a number of other metabolic and physiologic parameters, such as elasticity of the arteries (known as vascular compliance) which impacts on risk of heart disease, and glycaemic profiles.

This study showed that an intake of sucrose two and a half times above average consumption levels showed no adverse effects on this important marker of diabetes risk. This study does not therefore support the notion that sugar intake, within a broad range that covers the intake of the majority of British adults has any adverse effect on the risk of diabetes.

Diet can have a large impact on risk of type 2 diabetes; the strongest evidence for a link exists with saturated fat. Dr Hunter advises that the best way of reducing the likelihood of developing diabetes is through lifestyle changes. He adds it is likely that other dietary factors such as excess calories and lifestyle factors such as physical inactivity and weight gain may be more important than carbohydrate type.ť

In people at risk of type 2 diabetes, a diet rich in carbohydrate and low in fat appears to offer protection against insulin resistance. In addition, being of a healthy body weight and maintaining an active lifestyle will help reduce the risk of developing type 2 diabetes.

Insulin resistance is a common but often silent disorder which occurs when the body does not respond appropriately to the effects of insulin (see below). Insulin resistance can lead to, and is a feature of, the more serious condition, type 2 diabetes (non-insulin dependent diabetes). It is also an independent risk factor for atherosclerotic vascular disease. Any affect of a high sucrose diet on insulin resistance is therefore a reliable indicator of its likely influence on the risk of diabetes and atherosclerosis.

Insulin, a hormone produced by the pancreas, is needed for normal glucose, fat and protein metabolism. Insulin controls the amount of glucose in the blood by enabling glucose to enter cells (e.g. muscle and liver cells) which need glucose for fuel. With insulin resistance the body's cells do not respond fully to the effects of insulin and/or the body cannot produce enough insulin to overcome this defect. This ultimately leads to raised blood glucose. Having blood glucose that is too high (hyperglycemia) is dangerous to health, for example, long-term hyperglycemia is associated with an increased risk of kidney and eye problems.

Fat metabolism is also affected by insulin resistance raising the risk of heart disease, the most common cause of death amongst people with diabetes.

On a global scale, insulin resistance and type 2 diabetes are becoming increasingly common. Whilst genetics account for some degree of susceptibility to these disorders, lifestyle factors such as diet and physical activity levels can have a large impact on risk. Insulin resistance is closely involved in type 2 diabetes, and is thought to be a precursor to the disease.

DATE: December 22, 2006

Sensory nerve cells -- not immune cells -- may be the key culprits in type 1 diabetes, mouse studies suggest.

The findings, if confirmed in humans, would turn diabetes research on its head. They suggest that diabetes could be treated or prevented with drugs that work on the nervous system. The study is published in the Dec. 15 issue of /Cell/; it comes from the labs of Hans Michael Dosch, MD, PhD, and Michael Salter, MD, PhD, at The Hospital for Sick Children in Toronto. "We are now working hard to extend our studies to [type 1 diabetes] patients, where many have sensory nerve abnormalities," Dosch says in a news release. "But we don't yet know if these abnormalities start early in life and if they contribute to disease development."

Most researchers believe type 1 diabetes is a problem with the immune system attacking healthy cells.

These new findings suggest that haywire immune responses are tied to defective sensory nerve cells.

These cells, called TRPV1 neurons, respond to insulin by sending out powerful chemical signals, one of which is a pain-related protein called substance P.

Dosch and Salter's team finds that in diabetic mice, TRPV1 neurons send only a weak signal. When the researchers killed off the mice's TRPV1 cells, the animals' diabetes disappeared. And when they injected the animals' pancreases with substance P, most became diabetes-free. The researchers suggest that defective sensory nerves help start -- and maintain -- diabetes in diabetes-prone humans. "Our observations open new avenues for therapeutic strategies," Dosch, Salter, and colleagues conclude. They also say TRPV1 defects may play a role in other autoimmune diseases.Lupus and rheumatoid arthritis are examples of other autoimmune diseases. An editorial by University of California researchers Helene Bour-Jordan, PhD, and Jeffrey A. Bluestone, PhD, accompanies the Dosch and Salter team's report. Bour-Jordan and Bluestone say the new findings support a growing suspicion among researchers that autoimmune diseases arise from interplays between the nervous system and the immune system. However, they question whether the specific nerve defect seen by the Canadian team is the cause of diabetes, or simply something that happens to people as diabetes progresses.

DATE: December 15, 2006

A Canadian-led research team has uncovered the trigger for Type 1 diabetes, a "breakthrough" that allowed them to cure the disease in mice and could ease the suffering of millions worldwide. "This discovery, a breakthrough that has long been the elusive goal of diabetes research, has led to new treatment strategies for diabetes, achieving reversal of the disease without severe, toxic immunosuppression," the scientists said in a statement.

The findings by researchers at Toronto's Hospital for Sick Children, the University of Calgary and the Jackson Laboratory in Maine were published in the December 15 issue of the journal Cell. Type 1 diabetes is an autoimmune disorder that affects millions of people worldwide, about 10 percent of all diabetes cases. It arises when certain cells responsible for insulin production become inflamed and are ultimately destroyed, making it impossible for the body to produce insulin. Insulin deficiency is fatal and current insulin replacement therapies cannot prevent many side effects such as heart attacks, blindness, strokes, loss of limbs and kidney function. Most studies on Type 1 diabetes had focused on the immune system, but the Canadian-led team found a link between the disease and the nervous system.

The group discovered that abnormal nerve endings in insulin-producing pancreas islet cells sparked a chain of events that caused Type 1 diabetes in mice. When they removed the sensory neurons, it prevented inflammation of the cells and the mice did not develop the disorder. An injection also cleared islet cell inflammation in afflicted mice within a day and normalized the elevated insulin resistance normally associated with the disease. "We have created a better understanding of both Type 1 and Type 2 diabetes, with new therapeutic targets and approaches derived for both diseases," said study collaborator Pere Santamaria of the University of Calgary. "We are now working hard to extend our studies to patients, where many have sensory nerve abnormalities, but we don't yet know if these abnormalities start early in life and if they contribute to disease development." The treatment is now being tested for Type 2 or obesity-related diabetes, in which insulin resistance is even more severe, with "strong evidence" so far it will work, the researchers said.

DATE: December 08, 2006

Half of the estimated 21 million adult Americans with diabetes now rate themselves as having only "fair" or "poor" health, and people between 18 and 44 years of age are increasingly affected, a new report from the U.S. Centers for Disease Control and Prevention finds. In fact, people with diabetes are three times more likely than others to say their health is flagging, the CDC report found.

The news is troubling because "fair or poor health among persons with diabetes is also associated with the presence of diabetes-related complications such as lower extremity amputation, blindness, kidney failure, and cardiovascular disease," noted the editors of the CDC journal /Morbidity and Mortal//ity Weekly Report/, which published the findings last Friday. In the study, CDC researchers looked over 2005 data from the federal Behavioral Risk Factor Surveillance System, an ongoing survey of adult Americans' health and health risk factors. Among the poll's questions: "Would you say that, in general, your health is excellent, very good, good, fair, or poor?" According to the survey, almost half (49.3 percent) of those with diabetes said they were only in "fair" or "poor" health -- a number three times higher than that of people without diabetes. The rate of fair/poor health among people 45 and older with diabetes has remained stable over the past 10 years, hovering around 50 percent. But the CDC noted that health complaints are rising among younger Americans. Among people with diabetes aged 18 to 44, reports of fair/poor health rose from about 36 percent in 1996 to 43.4 percent by 2005, the researchers found.

Race and availability of insurance were also key to health. Hispanic Americans, especially, are 60 percent more likely than whites to note poor health linked to diabetes, and a lack of health insurance boosted the likelihood of poorer health by 70 percent, the study found. Diabetes care is becoming an increasing burden on the U.S. health care system, according to two other government reports released Wednesday. Between 1996 and 2003, the number of adult diabetes patients soared from 9.9 million to 13.7 million, and their individual annual spending on prescription drugs jumped almost 86 percent, from $476 to $883. According to the reports, from the Agency for Healthcare Research and Quality, overall care for patients with diabetes -- including treatment in and out of hospital and for other illnesses such as congestive heart failure -- averaged more than $10,000 annually.

The new diabetes statistics come on the heels of good and bad news from the federal government's annual Health, United States report for 2006, issued earlier in November. That report found that diabetes continues to be a growing threat, especially among older adults. Eleven percent of adults aged 40 to 59, and 23 percent of those 60 and older, have diabetes. The report also focuses on the problem of chronic pain. According to the report, 25 percent of adults say they've experienced pain that lasts at least one day, and 10 percent say they've lived with pain that persists a year or more. "We are living longer, and we have more chronic conditions," said lead author Amy Bernstein, chief of the analytic studies branch at the U.S. Centers for Disease Control and Prevention's National Center for Health Statistics. "Diabetes rates are increasing, obesity rates are increasing. And, as people live longer, they get more chronic conditions, including pain." According to the report, 21 percent of adults aged 65 and older said they had experienced pain in the past month that lasted for more than 24 hours. And almost three-fifths of adults 65 and older said their pain had lasted a year or more.

DATE: December 01, 2006

Researchers reported this week that a substance found in red wine recently shown to help laboratory mice live longer also protects animals from obesity and diabetes.

The new research helps confirm and extend the possible benefits of the substance, resveratrol, and offers new insight into how it works -- apparently by revving up the metabolism to make muscles burn more energy and work more efficiently. Mice fed large doses could run twice as far as normal.

In addition, the scientists produced evidence for the first time linking the biological pathway activated by the substance to humans, showing that the same genetic switch that resveratrol mimics seems to naturally endow some people with faster metabolisms.

"It's very exciting," said Johan Auwerx, professor of medicine at the Institute for Genetics and Cellular and Molecular Biology in Strasbourg, France, who led the research, which is being published in the journal Cell. "This compound could have many applications -- treating obesity and diabetes, improving human endurance, helping the frail. There's a lot of potential."

Auwerx and other researchers cautioned that much more research is needed to study the compound and similar agents, especially to see if the approach is safe for people. Humans would have to take hundreds of resveratrol pills sold in health food stores or drink hundreds of glasses of wine a day to get equivalent levels of the substance tested on the mice, neither of which would be safe.

But the new research adds to growing enthusiasm about the approach, experts said.

"This is the first example of a drug that can apparently affect the whole aging process, not just this disease or that disease, but the mechanisms that allow these diseases to occur," said Felipe Sierra of the National Institute on Aging.

Others agreed.

"The idea of giving someone anything to improve their longevity until very recently would have been considered snake oil or crockery," said Stephen Helfand of Brown University. "But here we are, possibly being able to move out of the laboratory from extending the lives of flies, worms and mice to humans, a lot sooner than we thought."

Resveratrol is found in red wine, grapes and other foods, including peanuts. Scientists suspect it may help explain why French people have fewer heart attacks despite their high-fat diets, and why eating a very low-calorie diet can lengthen the lives of many species.

Researchers recently demonstrated that resveratrol did the same thing for mammals in a study involving laboratory mice. High doses of the compound neutralized the ill effects of a high-fat, high-calorie diet, extending the animals' lives and preventing harm to their livers and hearts.

In the new study, researchers fed mice even higher dosages -- 10 times higher -- along with a high-fat, high-calorie diet. Resveratrol significantly reduced the animals' chances of becoming obese and of developing early signs of diabetes. The mice appeared to experience no harmful side effects.

Additional experiments on the animals' cells indicate the substance works by increasing the activity of an enzyme known as SIRT1, boosting the number and activity of structures inside cells called mitochondria, the researchers said. Mitochondria are like power plants inside cells, burning fat and providing energy. They tend to get revved up by exercise and to deteriorate with age.

The mice fed resveratrol had more efficient muscle tissue, sharply improving their endurance.

"In the elderly, many of the disorders that occur with aging occur because of muscle weakness," Helfand said. "This makes you wonder what would happen if you took an older individual and revved up their mitochondria with resveratrol. You could imagine that it could have a profound positive effect on their health."

Auwerx also wondered whether the substance might be abused by professional athletes. "That could be the illicit use of these compounds -- as performance boosters," he said.

In addition to the mouse experiments, the researchers also produced evidence supporting the theory that SIRT1 plays a key role in longevity in humans in an accompanying analysis of 123 Finnish adults. The subjects born with certain variations of the SIRT1 gene had faster metabolisms, naturally burning energy more efficiently, indicating the same pathway works in humans, too.

"We've all seen people who are thin no matter what they eat or do -- that have good metabolisms versus bad. This may help explain that," said Christoph Westphal, chief executive of Sirtris Pharmaceuticals of Cambridge, Mass., which sponsored and helped conduct the study as part of its effort to develop drugs based on the approach.

The company is already testing a potent version of resveratrol on diabetic humans and hopes to eventually test it and similar compounds as a treatment for a variety of diseases. "We are targeting a gene that controls the aging process," Westphal said. "Many diseases have a link to the aging process. So these kinds of drugs clearly have the potential to treat several diseases of aging."

Other researchers said the new work is interesting but remained cautious, particularly about making the link to SIRT1.

"I think that's part of the story, but that it would be a mistake to think that's all that's going on," said Matt Kaeberlein of the University of Washington.

DATE: November 24, 2006

People with type-2 diabetes can learn life skills for daily management of their disease during a free online workshop and study.

Without proper management, diabetes can lead to such complications as cardiac problems, high blood pressure, strokes and kidney failure.

The online workshop Self-Management @ Stanford: Healthier Living with Diabetes lasts for six weeks. Participants in the study will be followed for two years to determine how effective the Internet can be in helping people learn skills to manage their diabetes. It is hoped that participants will improve their blood pressure, cholesterol, blood glucose and weight. The investigators will also be looking for improvements in quality of life, exercise and depression.

The study is organized by the Stanford University School of Medicine’s Patient Education Research Center, which has been developing tools for chronic disease self-management for 20 years. Dr. Kate Lorig, a professor of medicine and a nurse who has long been involved in developing and monitoring patient self-management programs, is the principal investigator on the study. Lorig’s team said that diabetes patients often don’t get enough help from their primary health-care providers; they explain that their workshops are intended to complement instructions from patients’ physicians.

By teaching self-management skills to an audience online, researchers are aiming to reach people who are unable to attend community classes or who might not be interested in in-person gatherings. Participants need to be adults living in the United States with a physician-confirmed diagnosis of type-2 diabetes, who have Internet access and who have an e-mail account. Participants may not have received treatment for cancer in the past year or be pregnant.

During the six weekly workshops, two trained, lay facilitators, who also have diabetes, will moderate online groups of about 25 people with type-2 diabetes. Participants are asked to log on, at their convenience, two or three times each week for a total of less than two hours weekly. Sessions are highly interactive through e-mail, messaging and online discussion boards, but participants do not need to log on at the same time.

Workshop topics include: blood glucose management; healthy eating; understanding A1C, lipids, body mass index and blood pressure numbers; weight control; exercise; hypoglycemia; managing sick days; working with health-care providers, and managing emotions and relationships.

Participants will be randomly assigned to one of three groups: those who receive the workshop; those who receive the workshop and participate in a yearlong e-mail discussion group, or those in a control group who receive the usual care. All three groups will complete four online questionnaires about their health status; members of the control group will also receive a gift certificate after completing each questionnaire, as well as a copy of the book used in the workshop at the end of the two-year period.

To register for the workshop, go to the Self-Management @ Stanford page.

For more information, call 800-366-2624 or send e-mail.

Workshops are also being offered specifically for Native Americans who are living with diabetes. Click here for Registration for Native American workshops.

The study is funded by grants from the National Institutes of Health and the Robert Wood Johnson Foundation.

DATE: November 17, 2006

Joslin Diabetes Center, global leader in diabetes research, care and education, announced today a new free educational tool on its Web site – the Staying Healthy with Diabetes video series. The set of six short videos gives people with diabetes important information about the regular tests they need to have done to live a healthier life. Several of Joslin’s internationally recognized physicians are featured in these videos.

The number of Americans with diabetes approaches 21 million, and now 54 million Americans have pre-diabetes. Joslin’s Web site continues to be a key resource for those affected by the disease, providing an online diabetes library and the latest information about diabetes research and care at Joslin. The video series, which adds new audio-visual educational materials to Joslin’s Web site, gives details about the importance of incorporating these six tests into standard diabetes care.

"At Joslin, we believe that active participation through self management and empowerment form the key to successful treatment of diabetes," explains Martin Abrahamson, M.D., Medical Director at Joslin Diabetes Center. "These videos give people with diabetes details about what the six tests measure and guidelines on what the results should be. This allows patients to work closely with their healthcare team to achieve their personal goals and stay healthy with diabetes."

Click on the links below for information about the six tests:

• A1C Test: Presented by Dr. Martin Abrahamson – The A1C test reflects the average blood glucose level for a two to three month period prior to the test and measures how well diabetes is being controlled. Joslin recommends people with diabetes have an A1C done every three to six months, achieving a level of 7 percent or lower, while also checking blood glucose levels at home on a daily basis. Dr. Abrahamson states, Controlling blood glucose levels through A1C tests and home blood glucose monitoring are critical to staying healthy and avoiding the serious consequences of diabetes-related complications, including heart disease, eye disease and kidney failure."
• Blood Pressure Test: Presented by Florence M. Brown, M.D., Co-Director, Joslin and Beth Israel Deaconess Medical Center Diabetes and Pregnancy Program – Monitoring blood pressure levels is critical for people with diabetes. Joslin recommends blood pressure levels be taken at every doctor’s office visit, with a target of 130/80 mmHg or better, and if kidney complications from diabetes have already developed, the target should be at or below 125/75 mmHg. "Diet, exercise, losing weight, minimizing stress, and reducing salt and caffeine intake all have a positive effect on blood pressure levels," emphasizes Dr. Brown.
• Eye Exam: Presented by Deborah K. Schlossman, M.D., Ophthalmologist, Beetham Eye Institute at Joslin Diabetes Center – Diabetic retinopathy is the most common sight-threatening eye disease for people with diabetes, but vision loss due to diabetic retinopathy can be prevented in the majority of cases. Joslin recommends a three-prong approach to eye care: maintain excellent A1C levels; keep blood pressure and other health factors in check; and have an annual eye exam involving either pupil dilation (where the doctor places drops in the eyes) or specially validated photographs of the retinas (the back of the eyes). "Although there are a variety of treatments for diabetic retinopathy, the earlier it is diagnosed and care begins, the more effective the treatment," she advises. Even if there are no eye or vision problems, an eye exam should be performed yearly to monitor eye health and determine the best follow-up care or treatment.
• Foot Exam: Presented by Richard A. Jackson, M.D., Senior Physician, Joslin Diabetes Center – Poorly controlled diabetes can cause circulation problems and also can cause neuropathy, or damage to the nerves leading to a loss of feeling or sensation. Joslin recommends people with diabetes have their feet examined at least once a year for altered sensation, decreased circulation and/or infection. "Smoking has a huge impact on the likelihood of people with diabetes developing foot complications because it affects circulation and causes nerve damage," notes Dr. Jackson.
• Kidney Function Test: Presented by Robert C. Stanton, M.D., Chief of Nephrology, Joslin Diabetes Center – Diabetes is a leading cause of kidney failure across the globe. Joslin recommends an annual microalbumin urine test to detect the presence of protein or albumin. Patients also should have creatinine levels monitored and a GFR, or estimated glomerular filtration rate, calculated for early signs of kidney disease. "Twenty to 40 percent of people with diabetes develop kidney disease, but when diagnosed early and treated, patients have better odds for healthy kidneys," explains Dr. Stanton.
• Lipid Levels Test: Presented by Om P. Ganda, M.D., Director of the Lipid Clinic, Joslin Diabetes Center – Because research indicates that high levels of lipids, or blood fats, increase the risk of heart disease, Joslin recommends people with diabetes have their lipid levels screened at least once a year. Joslin recommends an LDL level of less than 100; for people with a history of heart disease, stroke or cardiovascular disease, an LDL of 70 or less is advised. Dr. Ganda comments, "People with diabetes need to get the LDL, or bad cholesterol, level as low as possible because it is the most important factor causing cardiovascular disease."

DATE: November 10, 2006

Yogurt enriched with fruit or made from soy could play an important dietary role for people living with Type 2 diabetes and high blood pressure, suggests new findings by University of Massachusetts Amherst researchers.

Led by Kalidas Shetty, the UMass Amherst scientists screened extracts from a sampling of dairy and soy yogurts for properties that could help keep diabetes and hypertension in check, such as the activity level of enzymes that help moderate blood glucose levels. The researchers found that fruit-enriched yogurts—especially those made with blueberries or made from soy—contain active natural compounds that may curb some aspects of diabetes, the researchers report in an upcoming issue of the /Journal of Food Biochemistry/. The findings provide a strong rationale for further clinical studies, and for incorporating “healthy diet design” into disease management strategies, says Shetty. “What one eats should be part of an overall approach to therapy,” he says. Doctoral students Emmanouil Apostolidis and Young-In Kwon collaborated with Shetty on the research.

Type 2 diabetes, which accounts for roughly 90 percent of U.S. cases, is often associated with obesity, high blood pressure and elevated levels of cholesterol. The disease is characterized by an abnormal rise in blood sugar right after a meal. This chronic high blood sugar, known as hyperglycemia, is associated with many of the complications that can arise from the disease, including the failure of various organs such as the kidneys, heart, eyes and problems with nerves and blood vessels.

Medications that prevent the spike in blood glucose often target certain enzymes—in particular, enzymes that are responsible for modifying carbohydrates before they can be absorbed by the small intestine. Carbohydrates are the major source of blood sugar and inhibiting these carb-altering enzymes—alpha-amylase and alpha-glucosidase—slows the body’s absorption of sugars. The researchers were also interested in a third enzyme—angiotensin-I converting enzyme or ACE-I—which plays a role in the constriction of blood vessels. Medications known as ACE inhibitors block the activity of this enzyme, and such medications are used in treating high blood pressure in both diabetic and non-diabetic patients. Such medications have been shown to be an effective strategy for diabetes management, yet they can have unwanted side effects, says Shetty. Previous research by Shetty and others found that certain plant compounds also play a role in blocking all three of these enzymes, opening up the possibility that foods rich in such compounds may provide health benefits, but without the adverse side affects, he says.

So Shetty and his team went to the local supermarket and bought peach, strawberry, blueberry and plain yogurts made by four different brands, including a soy brand. The researchers took samples of each yogurt, and tested their ability to inhibit each of the enzymes of interest, using water or a buffer solution as a control. Of all the sampled yogurts, soy yogurt enriched with blueberries packed the most punch, inhibiting the activity of all three enzymes tested, the researchers report. Peach and strawberry enriched yogurts also fared well in their ability to inhibit the carb-altering enzymes alpha-amylase and alpha-glucosidase. The researchers also tested the yogurts for antioxidant activity and the quantity of a group of plant chemicals known as phenols. Phenols and polyphenols are found in a wide variety of plants; they give red wine and tea their heart-healthy boosts and are especially prominent in dark-colored fruits and vegetables. The benefits of these compounds seem to come from their antioxidant powers—polyphenols scavenge cells for nasty free radicals such as reactive forms of oxygen. Free radicals can damage cellular machinery much the way that metal is turned to rust. The extracts from blueberry yogurts had the second-highest concentrations of phenols and the most antioxidant activity, the researchers found, beat out only by soy (even the plain soy yogurt had higher phenol content than any regular yogurt with fruit). The blueberry extracts also were the best at blocking the action of alpha-glucosidase, which was correlated with the amount of phenols.

There was much more variation in which extracts inhibited alpha-amylase and ACE-I, and it wasn’t necessarily correlated with phenol content says Shetty. Soy yogurts had the highest phenol content overall, and were the best at inhibiting ACE-I. A growing body of research indicates that diets rich in fruits and vegetables are associated with lower incidences of certain diseases, and plant compounds such as phenols are of increasing interest to scientists, says Shetty. How these dietary antioxidants mediate disease isn’t clearly understood, Shetty suspects that they stimulate the body’s own antioxidant enzymes to shift into a defense mode that protects tissues from chronic disease, many of which are associated with damaging free radicals. “The numbers of people with environment-related diseases are going through the roof,” says Shetty, noting that in the United States alone more than 20 million people are estimated to have diabetes. Worldwide estimates are that 170 million to 200 million people have diet-linked Type 2 diabetes, and the World Health Organization expects those numbers to double by the year 2030. “Poor communities and especially Native Americans are afflicted with Type 2 diabetes more than other communities,” say Shetty. "Cost-effective dietary changes are essential for fighting this disease, and traditional diets that have a higher content of these protective antioxidants are an important part of the solution. We should be able to use diet along with other therapies, and diabetes is a disease where this especially makes sense."

DATE: November 03, 2006

Fifty-four million Americans - that’s one in six of us -- have pre-diabetes and most don’t even realize it. Mark Schutta, MD, medical director of the Penn Rodebaugh Diabetes Center, is urging at-risk patients to be proactive and ask your doctor to give you a simple blood test for pre-diabetes - to arm yourself with information before the damage is done. It means you have blood glucose levels that are higher than normal and you could one day reach a high enough level that you would be diagnosed with having diabetes.

Diabetes is a disease that affects the body's ability to produce or respond properly to insulin and must be managed on a daily basis once diagnosed. If not, it can lead to several health complications including death. November is designated annually as American Diabetes Month.

“If you have pre-diabetes, there’s a 75% probability that you will develop diabetes within 30 years,” comments Schutta. “Our country is in the middle of a type 2 diabetes epidemic. Right now, if you’re born in the U.S., your risk of developing diabetes is one in three.”

Schutta says the reason for the high numbers is that diabetes is a “silent killer” and in the early stages of the disease, patients often have no symptoms. Schutta urges anyone at risk for diabetes to be screened. He adds, “If you knew you had pre-diabetes, you could still prevent getting diabetes through changes in diet and exercise. There are many health benefits to knowing you have pre-diabetes and ‘heading it off.’ If you wait until you have diabetes, the vascular damage to your body may already be done.”

You should be screened for pre-diabetes if:
• You have a known family history of diabetes.
• You are African American, Latino, Native American, Asian American or Pacific Islander.
• While pregnant, you developed gestational diabetes.
• You delivered a baby who weighed more than nine pounds.
• You have high blood pressure, high blood cholesterol, are overweight.

Diabetes is a chronic disease affecting more than six percent of the U.S. population or 21 million people. Diabetes is linked to heart and kidney disease, strokes and other serious health problems. Diabetes results when the body either does not produce insulin or cannot use it properly. Insulin is a hormone that your body needs to convert sugar, starches, and other food into energy for living. Although there is no cure for diabetes, it can be controlled.

DATE: October 27, 2006

Carrying two copies of a common variant of a particular gene doubles your chances of developing diabetes and puts you in a similar risk category to being clinically obese, according to a collaborative study led by UCL (University College London) researchers.

The collaborative team led by UCL Professor Steve Humphries studied the TCF7L2 gene, which was discovered to be implicated in diabetes earlier this year by a group working in Iceland. The new study followed healthy middle-aged men in the UK for 15 years, and found that carrying a common variant of the gene increased their risk of developing diabetes by 50 per cent. Carrying two copies of the variant gene increased the risk two-fold, to nearly 100 per cent. In the population as a whole, the impact of this gene on the risk of developing diabetes is as big as the problem of being clinically obese (having a body mass index over 30).

The study, published in the Journal of Molecular Medicine, also looked at White, Indian-Asian and Afro-Caribbean diabetes patients and found that the risk for carriers of the gene was essentially the same across all groups.

Professor Steve Humphries, of the UCL Centre for Cardiovascular Genetics, said: "Although being overweight is the major risk factor for developing diabetes, it is now becoming clear that an individual's genetic makeup has a big impact on whether or not they are going to develop diabetes.

"This is the first study that has followed healthy men and shown that carrying this risk gene has such a big effect. Because it is so common, and because the risk is so high, this gene seems to be causing as many cases of diabetes in the UK as obesity, which we know is the biggest risk factor.

"Our findings point to a whole new genetic mechanism which could be putting people at high risk of diabetes, and this needs to be explored. If we could understand more about this pathway, it could be possible to develop completely new treatment methods.

"In future it might be possible to use this genetic information to identify those at high risk, but the most important things to do to avoid becoming diabetic are to eat healthily, take moderate exercise and not to become overweight."

Currently, over two million people in the UK have diabetes and another 750,000 have diabetes but are unaware of it. People with diabetes are much more likely to develop heart disease and may also have other medical problems which can lead to kidney disease and blindness.

Scientists are not yet certain of the full role of the TCF7L2 gene, but it appears to be involved in switching on and off a host of other important genes, and is probably key in the pancreas (where insulin is made to control the sugar levels in the blood), as well as in fatty tissue and the gut. The actual mutation in the gene has not yet been found, and there are likely to be several different mutations acting in different people.

It is possible that this gene could become a therapeutic target, although it would be important to target TCF7L2 only in the specific tissue necessary to reduce risk of diabetes - for example, in the insulin-making cells of the pancreas. Treatment would need to be designed to avoid interfering with the gene's important functions in other tissues, which could otherwise cause unwanted side effects.

In terms of genetic screening, it might be useful in the future to include this gene in a panel of other genes that have important effects on risk of diabetes, if people carrying TCF7L2 variants were found to need a certain drug. Such an approach is already being piloted in a form of diabetes that starts in early adulthood (MODY), where different genes cause the disease and require different treatments.

Dr Angela Wilson, Director of Research at Diabetes UK which partly funded the study, said: "The findings of this research are very exciting, as Type 2 diabetes results from a complex mix of genetic and lifestyle factors.

"If we can improve our understanding as to why people with certain genes are more likely to develop diabetes, it will help us to find ways to identify those at risk with a view to enabling them to take preventative action by adopting a healthy diet, becoming active and ensuring they do not become overweight - which is a major risk factor for diabetes.

"It also opens up new avenues of research which have the potential to lead to new treatments for people with diabetes."

DATE: October 20, 2006

A new pill just might help people lose weight by taking the edge off the cravings that make dieting so painful. And an added bonus, lower blood pressure, blood glucose, and cholesterol levels as well. The drug, rimonabant, fights the drive to overeat by blocking receptors in the brain that bring on the "munchies" when they're activated by natural appetite-regulating chemicals. (As it happens, the chemicals behave a lot like marijuana, and their discovery in the 1990s was prompted by earlier research into how pot works in the body.) Rimonabant was approved in June for use in the European Union, where it goes by the name Acomplia. Manufacturer Sanofi-Aventis hopes for approval in the USA by the end of this year.

Besides helping to control appetite, the body system that rimonabant acts upon plays a role in regulating weight and the breakdown of glucose and fat, as molecules called endocannabinoids bind to receptors in fat, muscle, the gastrointestinal tract, and the liver. The system's many functions may explain why people taking rimonabant see improvement in a range of risk factors for heart disease and diabetes-their blood glucose, their cholesterol readings-that can't be explained by weight loss alone. "There's a growing body of evidence that in obesity the system is overactivated," says Louis Aronne, a professor at Weill Cornell Medical Center in New York who has studied rimonabant. "What we're doing with this treatment is to try to tone it down to a normal level."

One hitch: Side effects reported include anxiety and depression. Some experts worry that the trials haven't looked at people who were depressed before starting the drug. "You could make the argument that a lot of obese people have an increased tendency to be depressed," says Stephen Woods, a professor of psychiatry and director of the Obesity Research Center at the University of Cincinnati. "How the drug will affect the obese person who's depressed is an unknown."

DATE: October 13, 2006

Merck & Company is expecting government approval any day now of a new diabetes drug with potential annual sales of $750 million.

Januvia is designed to treat Type 2 diabetes by lowering blood sugar levels and, unlike other diabetes treatments, causes very few side effects.

“There really doesn't seem to be any downside to it,” says John Buse, president-elect of the American Diabetes Association, “whereas all the other drugs out there have some downside to them.”

However, Buse said, some other diabetes treatments appear to be more effective than Januvia in lowering blood sugar levels.

Merck officials dispute that assessment, arguing that Januvia is as effective as other treatments.

“We believe that Januvia is very efficacious,” said Dr. John Amatruda, vice president of clinical research for Merck.

Diabetes, a disease characterized by high blood sugar levels, afflicts nearly 21 million Americans, and was the sixth-leading cause of death in the U.S. in 2002. It is caused by a lack of insulin, a hormone that helps convert sugars, starches and other nutrients into energy. Diabetes can lead to stroke, heart disease, blindness, kidney failure, amputations and death.

Type 2 diabetes is the more common form, accounting for 90 percent to 95 percent of U.S. cases. Unlike Type 1 diabetes, which requires insulin injections, many people with Type 2 can control their blood sugar levels with diet, exercise and medications.

Januvia is one of a new class of drugs called dipeptidyl-peptidase 4 (or DPP-4) inhibitors, which work by enhancing the body's own ability to lower blood sugar, or glucose, when it is elevated, according to Merck.

“The mechanism of action of DPP-4 inhibitors is distinct from that of any currently available class of glucose-lowering agents,” Merck said in Januvia informational materials.

“Because they work through a different mechanism ... all [who suffer from diabetes] could benefit from this drug,” said Buse.

Januvia's FDA approval has been slated for “mid-October,” meaning approval is, “imminent, any day now,” said Jay Galeota, general manager of Merck's global diabetes franchise. Januvia was developed in Rahway, N.J., and will be produced in Italy. But it will be sold by Merck's Upper Gwynedd-based sales force.

Merck is not the only company expecting approval of a DPP-4 inhibitor. Novartis is developing a DPP-4 inhibitor called Galvus, which is expected to hit the market next year.

Both drugs show promise but both face the challenge of a long learning curve with diabetes patients and healthcare professionals, wrote a group of Goldman Sachs analysts headed by James Kelly in an April report.

“We ... remain upbeat on the opportunities for this product class and estimate sales of Galvus and Januvia in 2010 of $1.4 billion and $750 million respectively,” the Goldman analysts wrote.

Merck's 2005 sales were more than $22 billion. Some of its larger drugs generate billions in annual sales.

Prudential Equity analyst Tim Anderson is not making specific sales predictions but wrote in a July report that Januvia has “high commercial potential.”

Buse thinks the jury is out on whether practitioners will prescribe Januvia over other drugs that he said confer a greater benefit but have greater side effects. “To me, at least, it's completely unclear whether this is going to be a blockbuster drug that millions will take,” Buse said.

Amatruda said Januvia was tested on people with “mild to moderate” cases of diabetes. In those cases, in which patients blood sugar levels were 8 percent or less, Januvia reduced those levels by about eight-tenths of a percent. But in trials on people with blood sugar levels above 9 percent, it reduced blood sugar by as much as 1.4 percent, Amatruda said.

In head-to-head trials against Glipizide, a frequently used diabetes medication, Januvia caused side effects including hypoglycemia in only 4.9 percent of patients, compared to 32 percent for Glipizide, Amatruda said.

“It's very powerful in lowering glucose [blood sugar], but it has a side effect profile that's similar to a placebo,” said Amatruda.

DATE: October 06, 2006

Short or poor quality sleep is associated with reduced control of blood-sugar levels in African Americans with diabetes, report researchers from the University of Chicago in the latest issue of the Archives of Internal Medicine. The finding suggests that one inexpensive way to improve the health of patients with type 2 diabetes might be to improve the duration and quality of their sleep.

“Sleep is modifiable,” said Kristen Knutson, research associate (assistant professor) in the department of health studies at the University of Chicago and first author of the paper. “We've known for some time that skimping on sleep can impair glucose tolerance even for healthy people. Now we have evidence connecting chronic partial sleep deprivation and reduced blood-sugar control in patients with diabetes.” “Although we can't be certain whether sleep loss makes diabetes worse or the diabetes interferes with sleep, it only makes sense for everyone, but especially patients with diabetes, to give themselves the opportunity to get enough sleep,” Knutson said. The study focused on 161 African-American patients being treated at the University of Chicago Hospitals for type 2 diabetes. The researchers asked participants how much sleep they thought they needed at night and how much sleep they managed to get on weeknights and weekends. They also assessed the quality of their sleep using a standard 19-item questionnaire, the Pittsburgh Sleep Quality Index (PSQI).

To assess blood sugar control they measured glycosylated hemoglobin, a standard tool for management of patients with diabetes. Glycosylated hemoglobin, or HbA1c, reflects the average blood glucose level over the previous three months. A normal HbA1c result is between four and six percent. Higher levels represent poor glucose control. Patients with diabetes are considered to be under good control if they can keep their levels below seven percent. The researchers found that, on average, the 161 diabetes patients got very little sleep and had poor glucose control. Mean sleep duration was six hours a night. Only six percent reported getting eight hours of sleep on weeknights and only 22 percent reported getting at least seven hours. Seventy-one percent had poor sleep quality. The median HbA1c score was 8.3 percent. Many patients with diabetes have painful complications that can interfere with sleep. Even after the researchers excluded 39 patients who reported such pain, however, two out of three of the remaining 122 patients reported poor quality sleep. The average HbA1c among those patients was almost as high: 8.2 percent. Insufficient or poor quality sleep was closely associated with higher HbA1c results. For patients with no complications of their diabetes, a three-hour “perceived sleep debt”-the difference between how much sleep they felt they needed and how much they think they got-was associated with a 1.1 percentage-point increase in HbA1c levels, for example from 7.5 percent up to 8.6 percent.

For patients with at least one complication of diabetes-such as nerve pain, kidney damage or coronary artery disease-decreased sleep quality appeared to be more important. An increase of five points (out of 21) on the PSQI was associated with a 1.9 percentage-point increase in HbA1c, for example from 8.7 percent up to 10.6 percent. “The magnitude of these effects,” the authors note, “is comparable to those of widely used oral antidiabetic agents.” A long series of laboratory and epidemiologic studies has suggested that cutting back on sleep has a harmful effect on glucose control, insulin secretion and metabolism in ways that might increase diabetes risk, said Eve Van Cauter, professor of medicine at the University of Chicago and senior author of the study. The current study asks the question: is glucose control in subjects who already have diabetes adversely affected by too little sleep or poor sleep? "Our findings suggest, at least in this study population, that short or poor sleep is associated with decreased blood-sugar control in patients who already have diabetes," she said. "The growing tendency to burn the candle at both ends may be a significant contributor to the current epidemic of diabetes. One way to slow down this epidemic may be to avoid building a chronic sleep debt."

The MacArthur Foundation, the American Diabetes Association and the National Institutes of Health funded this study. Additional authors are Armand Ryden, of the University of Chicago, and Bryce Mander, now at Northwestern University.

DATE: September 29, 2006

In a large-scale test, transplanted pancreas cells eliminated the need for insulin in some diabetes patients, but for many the benefit was short-lived.In many cases where the treatment was initially successful, too many transplanted cells eventually stopped working. The authors of the study, published in the New England Journal of Medicine, said refining their methods should improve the success rate. Chief study author James Shapiro of the University of Alberta in Edmonton, Canada, said the transplanted cells seemed to stop working because not enough survived the initial transplant. "We've only got a small number of cells that end up engrafting and they're all having to work at maximum capacity," Shapiro said. "When an engine runs at 3,000 revs every minute of the day and doesn't get a break, eventually some of them start to burn out."

The technique, originally announced in 2000, has become known as the Edmonton protocol. This was the first international test of the method, to see if it could successfully be applied on a large-scale basis. It was designed to help people with Type 1 diabetes, an autoimmune disease that destroys the pancreas cells that produce the insulin needed to process blood sugar. Type 1 diabetes affects up to 2 million Americans. Processed pancreas cells from dead donors were given to 36 patients in North America and Europe. The treatment was tested in "the worst of the worst" patients, Shapiro said. A year later, 44 percent no longer needed insulin because the injected cells were processing blood sugar properly. Another 28 percent needed significantly less insulin. But at the two-year mark, 11 of the 16 patients who responded best were back on insulin. "Analyzed another way, 58 percent of subjects reached insulin independence at some point during the trial, but 76 percent had become insulin-dependent again by two years after transplantation," Jonathan Bromberg and Derek LeRoith of the Mount Sinai School of Medicine in New York wrote in a Journal editorial.

The study shows that more research is needed before this technique approaches the success rate of a regular pancreas transplant, they said. When a patient receives the entire organ instead of processed cells, the success rate is 50 to 70 percent after five years, Bromberg and LeRoith said. Both techniques carry risks because patients must take drugs that suppress the immune system and can have serious side effects. It is now clear that "institutions all over the world can successfully perform the protocol with at least short-term results that are promising," they said. "The problem remains that the medium- to long-term results are not durable, so much more work is needed." However, they said, the technique has come along way. Before Shapiro and his colleagues achieved a one-year survival rate of 80 percent for their transplanted pancreas cells, the success rate had been less than 2 percent.

An article By Gene Emery

DATE: September 15, 2006

Type 1 diabetes develops when your pancreas stops making insulin, what the body needs to break down sugar. Nobody knows why this happens, and there's no cure for it. Patients rely on taking insulin, but now, doctors say a drug could make that a thing of the past.Last year at this time, Ohio native Kaitlin Walsh-Reed was taking off on a plane for a trip to Florida. But today, the 17-year-old's plane landed 800 miles north, outside Indiana University School of Medicine in Indianapolis.

It's not exactly a vacation, but Kaitlin makes the trip every few weeks for medical care. She was diagnosed with type 1 diabetes four months ago. "When I first heard that I had it, I thought it was something like really bad," she recalled. "I was kind-of scared." Kaitlin's part of a new study on a drug called Rituximab. It targets the body's B-cells, which could preserve any insulin-producing cells a newly-diagnosed patient still has or even jump-start insulin production. "It has implications both in terms of prevention as well as achieving a cure," explained pediatric endocrinologist Dr. Henry Rodriguez, of Indiana University School of Medicine. "That they can find a cure for diabetes... I would love it," she said, but for today, Kaitlin's happy to just be going home.Rituximab is currently used to treat lymphoma, rheumatoid arthritis, and other autoimmune diseases. If the drug is effective for diabetes, it could reduce some of the long-term problems linked to it, like heart disease, vision loss and kidney damage. But researchers aren't there yet. In the meantime, Kaitlin will continue checking her blood sugar levels before each meal and keep careful records of her calories and carbs. But she hopes someday, she won't have to. "That they can find a cure for diabetes... I would love it," she said, but for today, Kaitlin's happy to just be going home. Rituximab is currently used to treat lymphoma, rheumatoid arthritis, and other autoimmune diseases. If the drug is effective for diabetes, it could reduce some of the long-term problems linked to it, like heart disease, vision loss and kidney damage.

BACKGROUND: According to the American Diabetes Association, type 1 diabetes, formally known as juvenile diabetes, is usually diagnosed in children and young adults and develops when the pancreas stops producing insulin. Insulin is necessary for the body to be able to use sugar. Sugar is the basic fuel for the cells in the body, and insulin takes the sugar from the blood into the cells. Patients must monitor their blood sugar levels by taking blood tests multiple times a day and take insulin through injections or inhalants, as there is no cure for the disease. In healthy people, a normally functioning pancreas monitors blood sugar consistently and delivers just the right amount of insulin to keep that blood sugar within the normal range.

UNDER STUDY: In a new international clinical trial led by doctors at the Indiana University School of Medicine in Indianapolis, patients who have been diagnosed with type 1 diabetes within the last three months are candidates, as they are still in the "honeymoon" phase of the disease. This refers to a patient still having between 10 percent and 30 percent of insulin-producing cells left. In this new study, patients are given injections of the B-cell targeting drug rituximab (Rituxan) in the hope that this honeymoon phase can be prolonged. Diabetes is easier to manage in this period, but ultimately, doctors hope it could lead to a cure. The first step would be preserving any insulin cells a patient has left and potentially make him or her less susceptible to some of the long-term consequences associated with the disease, such as heart disease, circulatory problems, vision loss, and kidney damage. The next step would be finding a way to stimulate the re-growth of insulin-producing cells, which would in essence produce a cure. One of the studies leaders, pediatric endocrinologist, Henry Rodriguez, M.D., says: "If we can determine that there is a means to safely prevent the immune system from destroying those insulin-producing cells, then, we then have something that we can take to those individuals that are at risk for developing the disease. Hopefully, at that point, we would have the situation where we could better identify individuals who are at risk and treat them with a safe therapy that would prevent them from developing diabetes to begin with." He adds, "This a therapy that has a potential of revolutionizing how we treat type 1 diabetes, whether or not we screen for it, outside of a research study, whether we can prevent it. So it has implications both in terms of prevention as well as achieving a cure. That is what I'm excited about."

RITUXIMAB: Doctors are essentially trying to alter the immune system so that it no longer recognizes insulin-producing cells as being foreign. Patients in the study receive rituximab weekly during the first four weeks of their participation in the study and will then be followed for two years -- and likely for a number of years after that. Doctors are looking for a primary outcome of a preservation of the ability to make insulin a year out. They will enroll 66 patients over two years at 15 centers. The study is funded by TrialNet ( http://www.diabetestrialnet.org )

DATE: September 08, 2006

It may soon be possible to manage the serious condition of diabetes naturally using nutmeg seeds (Myristica fragrans) according to new research presented this week at the British Pharmaceutical Conference in Manchester England.

Diabetes is a metabolic disorder that is estimated by the Department of Health to affect 2.35 million people in England alone, and this figure continues to rise. Diabetes is a serious condition by which the body is unable to break down sugar (glucose) in the blood due to a deficiency of insulin. People with diabetes often have raised fat (lipid) levels in the blood, which increases the risk of cardiovascular disease.

Nutmeg has been used across the world as a ground spice in cooking for centuries. In the tribal areas of India, where there is a lack of access to conventional medicine, nutmeg is also used for treating diabetes, as well as other ailments such as diarrhea, mouth sores, and insomnia. But to date there has been no scientific data to support its anti-diabetic activity.

Knowledge of nutmeg's traditional use led pharmacists in Pune and Sagar, India, to study nutmeg scientifically. Their controlled tests on rats showed that extracts of the spice:

• significantly decreases blood glucose levels
• improves the lipid profile in the blood
• stimulate the beta-cells of the pancreas to release insulin
• improves body and organ (liver and pancreas) weight

Somani, says that the research team now want to carry out some advanced studies to see how nutmeg can be used in the treatment of this common disease, possibly with an international partner.

DATE: September 01, 2006

People with diabetes might be able to reduce their blood sugar by using a cinnamon extract, a new study has found.

The number of people being diagnosed with adult-onset (type 2) diabetes has grown to about 150 million people worldwide, with more than 17 million in the United States. People with diabetes have high blood sugar levels because their cells don’t respond to insulin, the hormone that signals when glucose (the form sugar takes in the blood) needs to be stored. Over time, the extra glucose in the blood damages tissues.

Eating a high-fiber, low-sugar diet and exercising are important ways to keep blood glucose levels normal. Oral medications are also often used to reduce blood glucose levels, and in some cases insulin injections are necessary. Nutritionally oriented healthcare providers frequently recommend minerals such as chromium and magnesium. Some herbs such as gymnema and fenugreek have been found to have blood glucose–lowering effects.

Cinnamon (Cinnamomum cassia) is an aromatic herb with sweet and warming qualities. Its history as a medicinal herb goes back centuries in India and other parts of Asia, but it is better known in the Western world as a culinary spice. Animal studies and preliminary studies in humans have suggested that cinnamon has blood glucose–lowering effects that could help people with type 2 diabetes.

In the latest study, published in the European Journal of Clinical Investigation, 65 people with diabetes being treated only with diet or oral medications (not insulin) were given either a cinnamon extract (equivalent to 3 grams of cinnamon per day) or a placebo for four months.

Fasting blood glucose levels (measured after eight or more hours without eating or drinking) dropped 10% in those who used the cinnamon, but did not change in the placebo group. Blood glucose levels decreased the most in those who had the highest levels at the beginning of the study.

“More and more people are being diagnosed with type 2 diabetes, and many of them want to avoid oral medications and especially insulin injections,” said Linda Dacey, MD, who practices internal medicine. “Although the findings from this study are encouraging, for now it seems wise to wait until future research clarifies whether cinnamon works well enough to be used as a first-line treatment, along with diet and exercise, or whether it should be used in conjunction with oral medications.”

In the meantime, cinnamon is a safe and inexpensive addition to a program designed to help manage high blood sugar from diabetes.

Maureen Williams, Who received her bachelor’s degree from the University of Pennsylvania and her Doctorate of Naturopathic Medicine from Bastyr University in Seattle, WA. She has a private practice in Quechee, VT, and does extensive work with traditional herbal medicine in Guatemala and Honduras.

DATE: August 18, 2006

Reducing the size of abdominal cells, a risk factor for diabetes and heart disease, takes more than cutting calories, according to new research published on Wednesday by Wake Forest University. Early results show that exercise should be added to the equation, according to the study.

"The message is very clear," said the lead author Tongjian You, Ph.D., "Exercise is important to reducing the size of these cells, and may one day be part of a prescription for treating the health complications associated with abdominal fat." The study is reported in the August issue of the International Journal of Obesity. The results -- from 45 obese, middle-age women with excess abdominal fat -- are part of an ongoing study of up to 125 women. The goal is to determine what lifestyle changes are needed to reduce the size of abdominal fat cells. It is well known that overall obesity is risk factor for diabetes and heart disease. Obese people who have more abdominal ( an apple shape) are at a higher risk than people who store excess fat in their hips and thighs (a pear shape).

Abdominal fat is associated with metabolic syndrome, a cluster of symptoms that increases the risk for heart disease and diabetes. The current research studied a lesser-known risk factor for the syndrome -- the size of fat cells just under the surface of the skin, known as subcutaneous fat. Earlier studies had shown that exercise can reduce fat cell size, but it is not known if the intensity of exercise matters during dietary weight loss. For the current study, all women had a deficit of 2,800 calories a week, either through dieting or a combination of dieting and exercise. One group cut their calorie levels through diet, but did not exercise. A second group walked at about 1 to 2 miles per hour on a treadmill for 50 minutes three times a week. A third group also walked three times a week, but at 3.5 to 4 miles per hour for 30 minutes. Both exercise groups burned 400 calories each week through walking. The diet-alone group had no changes in abdominal fat cell size. However, both exercise groups had decreases of about 18 percent in the size of their abdominal fat cells. "These early findings do point to the importance of exercise in treating the complications of abdominal fat," Dr. You said.

DATE: August 11, 2006

BATON ROUGE, LA -- Results from a new study in patients with type 2 diabetes demonstrate that daily supplementation with 1000 mcg of chromium as chromium picolinate, in combination with a common oral anti-diabetic medication, improves insulin sensitivity and glucose control better than the oral anti-diabetic agent alone.

The study, conducted by researchers at Pennington Biomedical Research Center (PBRC) and the University of Vermont College of Medicine, is published in the August issue of Diabetes Care, an official journal of the American Diabetes Association.

The study also found that chromium picolinate significantly reduced the weight gain typically associated with the use of a commonly prescribed antidiabetic medication.1 These findings are significant as more than two-thirds of people with type 2 diabetes are not at the suggested goal for their blood sugar. Additionally, more than 80 percent of people with type 2 diabetes are overweight, which can significantly increase their risk of disease-related complications, including cardiovascular disease, which is the leading cause of death amongst patients with diabetes.

"The results further support that chromium may serve as a safe and effective adjunct to medication in helping people with type 2 diabetes improve their blood sugar control. In patients who take a sulfonylurea to control elevated blood sugar, weight gain is common. However, the study findings show that weight gain was less with use of supplemental chromium," said study investigator, William Cefalu, MD, chief of the Center's Division of Nutrition and Chronic Diseases. "Also important is that chromium picolinate helped reduce abdominal fat accumulation, which is associated with a greater risk for other conditions such as abnormal lipids and hypertension."

The 40-week randomized, double-blind, placebo-controlled, study was designed to examine the effect of adding daily chromium picolinate supplementation to an antidiabetic medication.1 Sulfonylurea, a commonly prescribed treatment for type 2 diabetes, was given to 29 subjects for 24 weeks, in conjunction with chromium picolinate or a matching placebo (sugar pill).1

Blood sugar levels of study participants taking chromium picolinate in combination with the antidiabetic medication dropped significantly compared to the group taking the medication plus placebo (-31.00 + 7.37 mg/dL vs. -11.33 + 8.03 mg/dL).1 In addition, insulin sensitivity, as measured by glucose disposal, for participants taking the medication along with chromium picolinate was increased when compared to those taking the antidiabetic agent and placebo.

Study participants taking chromium picolinate also experienced significantly lower abdominal body fat accumulation than the group taking medication and placebo, and experienced less overall weight gain (0.9 kg vs. 2.2 kg).1

"It's also important to note that no significant adverse events were reported among the study participants," added Cefalu.

The chromium used in this study was provided by Nutrition 21, the makers of Chromax® chromium picolinate.

DATE: August 04, 2006

Fatty acids commonly found in dairy products have successfully treated diabetes in mice, according to a researcher at Penn State. The compounds, known as conjugated linoleic acids (CLA), have also shown promising results in human trials, signaling a new way of potentially treating the disease without synthetic drugs. "The compounds are predominantly found in dairy products such as milk, cheese and meat, and are formed by bacteria in ruminants that take linoleic acids – fatty acids from plants – and convert them into conjugated linoleic acids, or CLA," says Jack Vanden Heuvel, professor of molecular toxicology in Penn State's College of Agricultural Sciences and co-director of Penn State's Center of Excellence in Nutrigenomics.

Researchers first became interested in CLA when it was shown to inhibit a variety of cancers such as breast, skin and colon in mice, and further research showed effects on circulating cholesterol and inflammation. These effects are the same as the newest generation of synthetic drugs used to treat diabetes in humans. These synthetic drugs act by triggering a set of nuclear receptors called PPAR. In addition to being targets for a variety of clinically effective drugs, PPARs belong to a large family of proteins, and their biological purpose is to sense fatty acids and fatty acid metabolites within the cell, says Vanden Heuvel. When the synthetic drugs interact with these protein receptors, it turns the receptor "on," making it an active form of the protein, which then interacts with DNA and regulates gene expression. This increases the enzymes that process fatty acids and also increases the tissues' sensitivity to insulin.

"We wondered if CLA was using the same mechanism, in which case it could be used as an anti-diabetes drug," Vanden Heuvel says. To test the idea, he used CLA on mice prone to adult onset (Type-2) diabetes. Results indicated that the mice had an improvement in insulin action, and a decrease in circulating glucose. Also, the mechanism was indeed similar to that of the drugs. "Anti-diabetes drugs act the same way. They mimic the natural activators of the receptors by getting into the cell and interacting with the PPARs to regulate glucose and fat metabolism," says Vanden Heuvel. Early human trials indicate that when administered for longer than 8 weeks, CLA improves the body's misregulation of insulin and lowers the level of glucose in the blood in patients with adult onset, or Type-2 diabetes, the most common form of this disease. However, Vanden Heuvel cautions that while having a diet that is high in dairy and meat products, and thereby CLA, might have a health benefit, one must also be aware of other lipids present in these products, such as trans fatty acids. Instead, he suggests that in addition to a well-balanced diet, it is advantageous to incorporate CLA as a dietary supplement, or to seek out new products that enrich foods such as butter, margarine and ice cream with CLA. "Adult-onset diabetes is fast becoming an epidemic and is largely associated with poor diet and nutrition and other lifestyle issues," Vanden Heuvel says. The reason for the increase in diabetes may have to do with the ratio of so-called "good" and "bad" fats, with the average American diet containing too much of the "bad" fats. CLA, whose effect is very similar to fish oil, a source of "good" fat, could prove beneficial against Type-2 diabetes. "And compared to the synthetic drugs used to treated this disease, CLA does not cause weight gain and may in fact decrease overall body fat," says Vanden Heuvel, who has been granted a patent on the new method of treating diabetes with CLA. Other researchers on the patent include Martha Belury, Ohio State University, and Louise Peck, University of Washington, for the work initially conducted at Purdue University. The Penn State Center of Excellence in Nutrigenomics is at nutrigenomics.psu.edu.

DATE: July 28, 2006

A British research institute will be allowed to recruit women having fertility treatment to donate eggs for stem cell research and therapeutic cloning. In exchange for their eggs, the Human Fertilization and Embryology Authority (HFEA) said on Thursday the institute would contribute to the cost of the patients' treatment. "We have made an offer of a license to Newcastle Fertility Center at Life which, if the conditions are accepted by the research team, would allow them to carry out an egg-sharing' scheme in which women who are already undergoing fertility treatment can donate some of their eggs for use in research in return for some of their treatment costs being met," said Angela McNab, the chief executive of the HFEA.

Therapeutic cloning involves creating early embryos to obtain stem cells -- master cells in the body that can develop into any other cell type -- to treat diseases. At present, only spare embryos left over from fertility treatments are used in stem cell research and scientists have been concerned about a shortage of eggs for research. Stem cell researchers hope the HFEA move will speed up progress toward therapies for illnesses such as diabetes, Alzheimer's and Parkinson's disease.

"The potential benefits of stem cell research in the treatment of degenerative diseases is so great that the prospect of increased availability of good quality eggs obtained via 'egg-sharing' is to be welcomed," said Dr Gillian Lockwood of the British Fertility Society. Therapeutic cloning is condemned by anti-abortion groups because it involves removing the stem cells and destroying the embryo. The egg-sharing scheme is not expected to be operating for at least 12 months while regulatory agreements and funding details are finalized. The HFEA made the offer to the center ahead of the start of a three-month consultation period that will begin in September during which it will consider views on the egg-sharing issue. There has been some concern about how scientists will obtain eggs for research, and fears women could be pressured into donating eggs or that their health could be put at risk. "We have made the offer on the understanding that the center will provide regular information to the HFEA on its progress. "The Newcastle team are also aware that should new policy be made as a result of the public consultation that the license committee are able to review the amendment to their license," McNab added in a statement.

By Patricia Reamey

DATE: July 21, 2006

As Congress and U.S. President George W. Bush squared off over stem cell research, potential treatments for diabetes, spinal cord injuries and other devastating disorders are still years away from human testing. How fast scientists can do key experiments to prove whether embryonic stem cell research will live up to its promise depends on how much money the federal government contributes, the key question as the Senate opened debate Monday on legislation to loosen Bush's restrictions. At issue is not whether human embryonic stem cell research will proceed or even if taxpayers will help fund it - they already do, $38 million US worth this year. The question boils down to exactly which embryonic stem cells are used in the race to develop treatments.

A limited number were created before 2001, many in ways that make human use problematic if not impossible. But there are potentially thousands of newer cells, culled from fertility clinic leftovers otherwise destined to be thrown away. Many scientists insist these would be better suited for implantation into sick Americans. Embryonic stem cells are essentially master cells, able to morph into all the cell types found in the body. If scientists could learn to control these cells and coax them into becoming specific types on demand, they potentially could grow replacements for damaged tissue - new insulin-producing cells for Type 1 diabetics or new nerve connections to restore movement after spinal injury, for example. The controversy revolves around the fact that scientists take those cells from a five-day-old embryo, when it's a ball of about 100 cells barely visible without a microscope, and the culling kills the embryo. Bush likened that to abortion when, on Aug. 9, 2001, he restricted government funding to research using only the embryonic stem cell "lines" then in existence, groups of stem cells kept alive and propagating in lab dishes. The new legislation, which passed the Senate but was vetoed by Bush, wouldn't fund the creation of new stem cell lines - nor any embryo destruction - but would let the National Institutes of Health fund research using newer stem cells in the pursuit of treatments.

Five states are funding embryonic stem cell research themselves. California voters approved a $3 billion initiative now being fought in court. Connecticut has a 10-year, $100-million initiative. Illinois spent $10 million last year. Maryland has approved a $15-million budget and New Jersey has spent about $25 million in two years. In the Senate, opponents argued against the need to work with embryonic cells, saying adult stem cells found in various tissues, such as blood-producing stem cells in bone marrow or umbilical cord blood, provide an embryo-free alternative. "We do not need to treat humans as raw material," Sen. Sam Brownback, R-Kan., said Monday. "It is immoral for us to do it." Scientists are avidly studying adult stem cells, too, with roughly $200 million in financial aid from the NIH this year, far more than for embryonic stem cells. But despite 50 years of research so far, adult stem cells' main use today is for bone marrow transplants to counteract intense cancer chemotherapy or to treat only a handful of other disorders, researchers wrote in the journal Science last week. "The politicians kind of set us up against each other but . . . the scientists are not arguing about this. We are working together," University of Minnesota stem cell researcher Meri Firpo said in an interview. She has worked with all types and created two of the Bush-approved embryonic stem cell lines and 11 newer lines with private money. Added Dr. Harold Varmus, a Nobel laureate and former NIH director: "I do believe in the very long run it will be possible to learn enough about how cells change their behaviour to take perhaps any kind of cell and make it do anything." But that's harder to do and could take far longer, while the first embryonic stem cell studies in people might begin within five years, he added.

So what are the biggest hurdles for embryonic stem cells? They involve both science and paperwork, and Minnesota's Firpo embodies both: -In her quest to develop insulin-producing cells to treat diabetes, she runs one lab for her NIH-funded research and a separate lab for research funded by her university and private groups, even though both labs do the same studies. Because private grants are smaller than NIH's multiyear grants, her privately funded experiments go into the freezer when that money runs out and she has to raise more. -Firpo created her newer stem cells in ways safer for transplantation. When she created her two Bush-approved batches, "we never thought these cell lines would be used clinically," she explained, describing how basic researchers don't follow the Food and Drug Administration's rules for actual therapies. -Scientifically, researchers are reporting great strides in getting embryonic stem cells to form the tissues they want. The question is whether they'll continue to work properly when implanted into the body, a big safety question. "They need to stay in the right place, stay alive and need to function correctly. Those are the parts we're just beginning with," says Firpo. "It's hard to predict what timeline that's going to take."

Source: Lauran Neergaard

DATE: July 07, 2006

Keith Szymkowiak had been going to a treatment center for four hours of dialysis three times a week after kidney failure almost seven years ago. His life centered around trips to Wisconsin's Gundersen Lutheran's dialysis centers. But during the past four months, Szymkowiak has found freedom with a new type of do-it-yourself dialysis at home. The 55-year-old Onalaska diabetic is the first in the La Crosse area to use a new system of home dialysis, which provides shorter, more frequent and possibly even more effective treatments. The treatments -- which last for two hours a day, six days a week -- more closely mimic his kidneys' natural functions and ease many of the side effects that come with traditional dialysis. Szymkowiak said he now gets a chance to choose his time for dialysis, but more importantly, he feels like his life has been transformed. "Now it feels like my kidneys are actually working," Szymkowiak said. "I have more energy, and I feel so much better. I don't think I could go back to regular dialysis. "Everyone's flabbergasted at how well I'm doing."

Home dialysis has been around for many years, but the dialysis machines have been big and cumbersome and required special plumbing, said Dr. Wilfrido Yutuc, a kidney specialist at Gundersen Lutheran for more than 40 years. Yutuc said home dialysis is starting to gain popularity as technology makes it easier for patients to treat themselves at home. At the forefront of the movement are medical device-makers, such as NxStage of Massachusetts, that have developed equipment that's simple enough for patients to operate and fits in their homes. The method is hemodialysis, which runs the blood from the patient's body through a dialysis machine and back again to clean the blood. NxStage broke ground last year with its introduction of a 75-pound machine for home dialysis. It looks like a 13-inch TV set, uses standard electrical outlets and doesn't need special plumbing connections or permanent installation. More than 100 dialysis centers in the U.S. now offer NxStage's system. Szymkowiak is now one of three Gundersen Lutheran patients on the system. "It's portable dialysis," Yutuc said. "You can take it with you for the weekend or vacation, and you set the time for dialysis. It fits easy into one's lifestyle, and patients gain more independence." Patients also have better control of their blood pressure, often reduce the number of medications and may not be hospitalized as often because the home dialysis system may help prevent complications, Yutuc said. Szymkowiak already has seen the health benefits. His blood pressure is lower, and he has reduced the number of medications he takes from more than 30 to nine. High blood pressure is Szymkowiak's enemy because he has major heart problems.

Szymkowiak was diagnosed with type I diabetes in 1980 and took six to eight insulin shots a day until four years ago when he received an insulin pump, a small device programmed to automatically and continuously deliver small amounts of insulin around the clock. In December 1999, Szymkowiak was ill and ended up in a Texas hospital, where he was diagnosed with kidney failure. He later was treated for several heart attacks and a stroke. He moved to La Crosse in 2001 and continued dialysis at Gundersen Lutheran. Szymkowiak said he is not eligible for a kidney transplant due to his heart problems. He will be on dialysis for the rest of his life. "The saying goes that nobody dies from kidney failure," Yutuc said. "I've had one patient who was on dialysis for 24 years. You die from other things such as stroke or heart attack." Szymkowiak plans his home dialysis treatments around his wife's work schedule. In late afternoon, he takes about 40 minutes to prepare for his treatment. The dialysis machine sits in a basement room equipped with a stereo and video system. He opens bags of dialysis solution and sets up the tubing and accessories he'll need for that day's treatment. When his wife, Shirley, comes home from work, he inserts needles into his arm, and he's ready for dialysis. Szymkowiak passes the time on a couch watching TV or movie, or listening to music. The dialysis machine has alarms to signal a malfunction or improper setup, and help is only a phone call away, he said. He is preparing to take his dialysis machine on the road for a week -- supplies will be sent to his destination. Szymkowiak had about a month of training before he started his treatment at home. "Learning how to set up the machine is not that hard," Szymkowiak said. "It becomes routine after a while." But Yutuc said, "Not everyone is a candidate for home dialysis. They have to have confidence in themselves and feel comfortable with the setup." Jane Brodrick, a Gundersen Lutheran registered nurse, said people who are successful at home dialysis often have a supporting partner. "They're also not afraid to do the setup and feel they can handle it," she said. Jane Welch, another Gundersen Lutheran registered nurse, helped Szymkowiak with his home dialysis machine. "Keith is doing very well and is committed to make it work," Welch said. Szymkowiak said he's always trying to buy more time with his life, and home dialysis makes his life easier. "I'm on borrowed time already," he said. "God had six chances to take me, and I'm still here. I'm going to enjoy it as along as I can."

For patients with kidney failure, there are just three options to filter toxins from their bodies and replace some of the organs' functions. Without those treatments, they would die. Peritoneal dialysis, which uses the body's own peritoneal membrane inside the abdomen to remove impurities. It can be performed at home but must be done every day and is feasible only for certain patients. About 8 percent of dialysis patients use this method, according to the most recent federal data available. Gundersen Lutheran has about 25 patients using this method of home dialysis. Hemodialysis, which runs the blood from the patient's body through a dialysis machine and back again. The treatment cleans the blood, but many patients feel wiped out. Typically, patients visit a clinic three times a week for four-hour sessions. Hemodialysis also can be done at home. Kidney transplant can offer some patients greater freedom, with fewer diet restrictions than the other treatments. But organ recipients have to take medicine to prevent rejection of the kidney, and there's a shortage of donor kidneys. About 130,000 patients had transplanted kidneys in 2003, according to federal data.

Sources: McClatchy Newspapers and Gundersen Lutheran Medical Center

DATE: June 30, 2006

Millions of diabetics face a lifetime of daily injections to replace the insulin their bodies fail to produce, as well as a host of risks that includes blindness, amputation, kidney failure, and heart disease. For many, particularly those afflicted with juvenile diabetes, transplants of the pancreatic tissue in which insulin is produced might alleviate these problems. Unfortunately, there are not nearly enough organ donors available for transplantation.

Insulin-producing pancreas tissues from animals could potentially provide a nearly unlimited supply for transplantation. But until now, attempts to transplant such animal tissues into non-human primates have evoked a fierce immune response. However, embryonic tissues, such as those from pigs (in which the insulin-producing cells are similar to those of humans), might not be rejected as strongly. New research by Prof. Yair Reisner of the Weizmann Institute's Immunology Department in Rehovot Israel, has brought the possibility of transplants from pig embryos one step closer. The results of the study appeared in the June issue of PLoS Medicine.

In previous work, Reisner and his team had shown that each embryonic organ has its own "time window" during which the chances for successful transplantation are optimal. Prior to this window, the early tissue's cells, which are still largely undifferentiated, can give rise to tumors. Past the window, however, they may be too well-developed: The host identifies these cells as foreign, causing the body to reject them. By transplanting tissues from pig embryos into mice lacking proper immune systems, they determined that the best time frame for pancreatic tissue was about a third of the way through gestation (from 42 to 56 days).

In the new study, Reisner's team wanted to see if such tissues could function in the body. They first implanted embryonic pancreatic tissue from pigs into mice that lacked an immune system of their own, but had human immune cells injected into them. From this experiment they learned that tissues taken at 42 days (within the time frame they had previously determined) exhibited a markedly reduced immune response.

Next, the team tried the experiment on mice with fully functioning immune systems, but destroyed the insulin-producing cells in their pancreases before proceeding with the transplant. With the aid of relatively mild immune suppression protocols, the implanted tissues were fully functional over time, producing insulin and maintaining the mice's blood sugar at normal levels.

"The results of this study," says Prof. Reisner, "warrant further, pre-clinical research on primate models."

Prof. Reisner is the incumbent of the Henry H. Drake Professorial Chair in Immunology, and his research is supported by numerous grants and private trusts including the J & R Center for Scientific Research.

DATE: June 23, 2006

Having just celebrated its first on-air anniversary, dLife TV, FOR YOUR DIABETES LIFE! has walked away with no less than four prestigious Telly Awards, including two top honors.

dLife TV, a LifeMed Media Company, is an innovative and pioneering television series dedicated to empowering the millions of Americans living with diabetes. The weekly talk/magazine format show delivers leading experts, timely medical information, inspirational stories and recipes for healthy eating. This ground-breaking television show strives to produce timely information motivating patients as well as their families, friends and caregivers.

Founded in 1978, the Telly Awards has become the premier award honoring outstanding local, regional, and cable TV commercials and programs, as well as the finest video and film productions. Winners and finalists represent the best work of the most respected television production companies, television stations, cable operators, and corporate video departments throughout the world.

A prestigious judging panel of over 25 accomplished industry professionals upholds the historical standard of excellence that Telly represents. Judges evaluate entries to recognize distinction in creative work.

dLife scooped up two bronzes and two silvers, the silvers being the highest recognition possible.

Top Telly honors went to dLife's "The Story of Insulin" in the documentary category and to "Diabetes Epidemic/Diabetes Research/Diabetes and Kidney Complications" in the health & fitness category.

dLifeTV airs every Sunday evening on CNBC, 7:00PM ET, 6:00PM CT and 4:00PM PT, every Sunday morning on DIRECTV channel 251, 7.30AM ET; and six days a week on CoLours TV on DISH TV Channel 9407.

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

DATE: June 16, 2006

Diabetes is a tough disease to manage – primarily because it requires a heavy dose of self-management – so anything that makes that management simpler is likely to get significant uptake. That concept is emerging as an overriding theme, perhaps even more so than in the past, at this year’s 66th annual scientific sessions of the America Diabetes Association (Alexandria, Virginia) ongoing in Washington.

Thus, Eli Lilly (Indianapolis) and Alkermes (Cambridge, Massachusetts) are riding the main wave as they rolled out at the meeting new studies which push forward the potential commercialization of their combined work: administration of a Lilly insulin product delivered by Alkermes’ AIR Inhaled System.

Additionally, Lilly was demonstrating its HumaPen Memoir, an electronic pen injection device with a feature that “remembers” previous doses of insulin.

Lily and Alkermes are hoping that they can be the second to offer an inhaled insulin product, following the approval, this past January (Medical Device Daily; Jan. 31, 2006), of Exubera, the first inhaled insulin product developed jointly by Pfizer (New York) and Nektar Therapeutics (San Carlos, California), with analysts saying that together, and perhaps even separately, inhaled insulin will reach the high ground of “blockbuster” sales status.

The new safety studies position Lilly and Alkermes to develop a product that can be used by those with both diabetes and breathing problems – asthma and chronic obstructive pulmonary disease (COPD), an application that was recommended against by the FDA panel reviewing Exubera, according to Doug Muchmore, senior medical scientist, Medical Fellow II, for Lilly.

He told Medical Device Daily that Pfizer and Nektar had supplied some study information to the FDA panel concerning safe use of Exubera in cases of COPD, but that the studies by Lilly and Alkermes are the first to be published and showing safety in these uses. Continued positive results, he said, would likely be used to seek the broader indications for the AIR system.

Thus, the studies reported on at this year’s ADA meeting were not broad-based but focused narrowly on the use of the system in COPD.

Muchmore told MDD that the company also has just completed enrollment of pivotal Phase II safety study, noting this as a “major milestone” in the companies’ clinical development programs for the AIR/insulin combination.

He declined offering timelines for regulatory filings or potential commercialization of the product given “the complexities and interactions” of what is required.

In the collaboration, Muchmore said Lilly is supplying the bulk insulin product – an unmodified human insulin, chemically identical to human insulin – and then providing a range of expertise for the trials.

The role of Alkermes has been to reformulate the insulin for the inhaler device and do the packaging into blister packs and foil pouches.

He described the special formulation as having two key characteristics: large particle composition of the insulin, but with low density, so as to need low energy to get into the lungs. Together, these features enable, for the insulin product, “a high level of consistent dose delivery [requiring only] regular breathing.”

The studies reported at the ADA meeting take into account that 10 million people in the U.S. – according to the National Heart, Lung, and Blood Institute (Bethesda, Maryland) – have COPD and that it may be a risk factor, particularly among women, for developing Type 2 diabetes.

Klaus Rave, MD, of Profil Institute for Metabolic Research (Neuss, Germany), said, “Because of COPD’s prevalence and its potential correlation with Type 2 diabetes, particularly in women, it’s important to study the safety, efficacy and predictability of AIR insulin in many patient populations, including in people with compromised lung function.”

Specifically, the studies analyzed the effect, in Type 1 and Type 2 diabetes, of these patients’ COPD on inhaled insulin absorption and action; the importance to patients of simple, patient-directed training of an inhaled insulin system; and dosing flexibility with the AIR insulin system.

The company’s Phase I study, “Pharmacokinetics (PK) and Glucodynamics (GD) of Human Insulin Inhalation Powder (HIIP) in Subjects with Chronic Obstructive Pulmonary Disease (COPD),” is, according to Lilly and Alkermes, the first published analysis of the effect of COPD on inhaled insulin absorption and action. Designed to evaluate the impact of compromised lung function on inhaled insulin dose delivery, the study found that the absorption and action of AIR insulin was reduced by a consistent amount in the presence of COPD.

The results also demonstrate that AIR insulin was able to deliver similar results on different days in patients with or without COPD and was “generally well-tolerated.”

In this open-label, randomized, three-period crossover trial, pharmacokinetic and glucodynamic responses to AIR insulin were compared with subcutaneous insulin lispro in 15 non-smoking healthy subjects (mean age 38) and 30 non-smoking subjects with moderate COPD – 15 each with chronic bronchitis (mean age 53) and emphysema (mean age 58) – using standard glucose clamp methodology, a process for measuring the absorption of and an individual’s response to insulin.

Subjects received two single doses of AIR insulin and one dose of subcutaneous insulin lispro. Pharmacokinetic and glucodynamic measures were assessed using blood tests, and safety was assessed using pulmonary function tests (PFTs) before and after each clamp and by spirometry, performed four times during clamps.

Key results: Total insulin exposure and metabolic effect after subcutaneous insulin lispro were comparable in all three groups. Compared with healthy subjects, AIR insulin absorption was reduced by 22% in subjects with emphysema and by 44% in those with chronic bronchitis. The metabolic effect of the AIR insulin dose was reduced in emphysema subjects and chronic bronchitis subjects.

AIR insulin was well-tolerated by these patients, measurements showing no difference between AIR insulin and subcutaneous insulin lispro treatments, with modest decreases in forced expiratory volume and forced vital capacity in both COPD groups.

A poster presentation, “A Comparison of Standard vs. Intensive Training on Usage of the Human Insulin Inhalation Powder (HIIP) Delivery System in Type 2 Diabetes (T2D) Patients,” reported on a Phase II trial in people with Type 2 diabetes, designed to compare two levels of training intensity, either standard/patient-directed training, or intensive/provider-coached training for the AIR insulin system on overall blood glucose levels.

Key results: the AIR insulin system is easy to use and can be supported by simple, patient-driven training while helping patients manage blood sugar levels. Both training methods had similar rates of compliance with training directions, and similar safety profiles. AIR insulin exposure was also similar between groups.

Besides other studies focusing on key attributes of the AIR insulin system, Lilly was demonstrating its HumaPen Memoir device, the term “memoir” referring to the device’s ability to provide the time, date and amount of the last 16 insulin doses delivered. Looking very much like a standard fountain pen, the device features a small clear viewing window at one end providing the information via digital display.

The HumaPen can inject from one to 60 doses of Humalog from a small cartridge. Humalog is the flagship insulin from Eli Lilly, introduced by Lilly as the world’s first insulin analog. Humalog can be taken within 15 minutes before or immediately after a meal, enabling patients to adjust the dose according to when they eat, what they eat and how much they eat.

FDA-approved – and in use in Europe for several years – the HumaPen will get commercial rollout in the U.S. this fall, according to Lily.

SOURCE-Medical Device Daily

DATE: June 09, 2006

Scientists at Johns Hopkins have uncovered a surprising and novel way of lowering blood sugar levels in mice by manipulating the release of sugar by liver cells. The results, published in the June issue of Cell Metabolism, have implications for treating conditions like diabetes.

The discovery by researchers in Hopkins' Institute of Basic Biomedical Sciences and McKusick-Nathans Institute for Genetic Medicine reveals that a protein called GCN5 is critical for controlling a domino-like cascade of molecular events that lead to the release of sugar from liver cells into the bloodstream. Understanding the role of GCN5 in maintaining blood sugar levels is leading to a clearer picture of how the body uses sugar and other nutrients to make, store and spend energy. "Understanding the ways that energy production and use are controlled is crucial to developing new drugs and therapies," says the report's senior author, Pere Puigserver, Ph.D., an assistant professor of cell biology at Hopkins. The inability to properly regulate blood sugar levels leads to conditions like obesity and diabetes. Both type 1 and type 2 diabetes cause blood sugar levels to stay too high, which can lead to complications like blindness, kidney failure and nerve damage.

"Diabetes is a really big problem, even when patients are given insulin and stay on strict diets," says Carles Lerin, Ph.D., a postdoctoral fellow in cell biology at Hopkins and an author of the report. "In the absence of a cure for the disease, we are really trying to focus on finding better treatment because currently available methods just don't work that efficiently," he says. The body keeps blood sugar - known as glucose - within a narrow range. Extra glucose floating through the bloodstream, which is common after eating a meal, is captured and kept in the liver. When blood glucose runs low, the liver releases its stores back into the bloodstream. When those reserves are tapped out, liver cells turn on genes to make more glucose to fuel the body.

The research team found that GCN5 chemically alters another protein called PGC-1alpha that normally turns on a set of genes to manufacture enzymes required for glucose release. When GCN5 is fully functional in liver cells, this cascade is turned off and glucose is not released from those cells. Removal of functional GCN5 from liver cells restores the cells' ability to release glucose. The researchers showed that GCN5 alters its target, sabotaging it by adding a chemical tag called an acetyl group. By using molecules that glow fluorescently, the researchers saw under high-power microscopes that GCN5 carries its tagged target to a different location in the cell's nucleus - sequestering it away from the genes it's normally meant to turn on. "GCN5 has been generally shown to turn on genes. No one knew that GCN5 could be used to turn off pathways" says Lerin. "It was a bit of a surprise." When the researchers put GCN5 into live mice, they found that it can in fact decrease blood glucose levels. Liver cells in mice that were given no food for 16 hours actively release glucose into the bloodstream. Introducing GCN5 into their livers, however, causes blood glucose levels in these mice to be reduced. "These results show that changing GCN5 is sufficient to control the sugar balance in mice," says Puigserver. "Therefore, GCN5 has the potential to be a target for therapeutic drug design in the future."

The researchers were funded by the Secretaria de Estado de Universidades e Investigacion del Ministerio de Educacion y Ciencia of Spain, the Ellinson Medical Foundation, the American Federation for Aging Research and the American Diabetes Association. Authors on the paper are Lerin, Joseph Rodgers, Dario Kalume, Seung-hee Kim, Akhilesh Pandey, and Puigserver, all of Hopkins.

On the Web: www.hopkinsmedicine.org

DATE: May 26, 2006

More than half of the 185,000 amputations in the U.S. each year are a result of diabetes, a disease that plagues an estimated 20.8 million Americans -- seven percent of the population -- and is on the rise. Diabetic neuropathy, nerve damage that causes a loss of sensation in the hands and feet, can allow small injuries to go unnoticed and become severely infected. Tight control of blood sugar can keep neuropathy at bay, but there is no cure.

"There are a variety of medications that are available now that can help with the pain but unfortunately, there's nothing available to help with numbness or prevention of nerve damage," says diabetes specialist Mark Kipnes, MD, director of the Diabetes and Glandular Disease Research Clinic in San Antonio, Texas.

But now Kipnes is leading the first human testing of a new drug that might prevent or even reverse such damage. Designed by researchers at Sangamo Biosciences, it uses a natural protein that turns on the patient's own gene for helping nerve growth. As the researchers wrote in the journal "Diabetes" tests on diabetic rats showed that repeated treatments with the drug led to increasingly improved nerve function.

Sangamo biochemist Philip Gregory notes that this Phase 1 clinical trial is the first human test of an entirely new class of drug that could turn any gene on or off depending on the disease. "These proteins are natural proteins that exist in essentially every human cell, there are thousands of them, they naturally regulate genes in cells," Gregory explains.

These gene-regulating proteins have an important feature called a zinc finger domain. The zinc finger region, whose structure was discovered by Nobel laureate Aaron Klug, is a finger-shaped structure containing a zinc atom. Unlike most proteins, those with these special domains can actually bind to DNA and act as transcription factors -- telling specific genes to turn on or off.

"So what we're able to do is to engineer these proteins so that they can bind to different genes of our choice," says Gregory. In this case, the gene targeted by the Sangamo team was one encoding a protein called VEGF-A, a natural growth factor.

"In diabetes, patients have significant blood sugar changes that give rise to the production of toxic byproducts in tissues that drive, essentially, a poisoning of the nerves," says Gregory. He explains that because VEGF-A naturally stimulates regeneration of nerves and the blood vessels that nourish them, it can reverse the damage caused by the glucose-driven degeneration.

"It's not that diabetic patients lack the gene for VEGF-A," explains Gregory, "They continue to have the gene and they produce VEGF-A, but it's like the patient's cells don't realize they could be more protected or suffer from the disease much less if the cells produce more of this particular protective factor." Gregory says that this gene therapy is more of an addition strategy -- they're simply adding more of the gene that's already present in the cells.

Gregory says turning on the gene should also have an advantage over strategies that just give patients the VEGF-A protein. "The natural form of VEGF-A is actually a family of factors," he says, and the researcher believe that, "it's that entire set, that entire family of factors that drive the full biological response. So putting in just one piece of the puzzle is not sufficient. You have to provide them all, and this is the most efficient way of doing that."

While patients in the Phase 1 trial tolerated the drug well it needs to be tested for longer time periods to prove its safety -- particularly since this treatment would need repeated administration. As Gregory explains, "Obviously this is a chronic disease and we need to have a chronic treatment, if you like, for such a disease."

Kipnes is excited about the prospect of having a treatment to offer people with diabetic neuropathy, but he points out that there may be some risks. As he points out, injecting a growth factor into body could theoretically encourage other, unwanted things to grow. "So these patients are very carefully screened for any kinds of cancers and tumors," he says.

The researchers report there's been no evidence of carcinogenesis in their animal studies. They also say that some patients in the safety trial showed some anecdotal improvement in their nerve function. Kipnes is currently recruiting patients for a second safety trial as well as a larger Phase 2 trial of the drug's effectiveness. Both are scheduled to begin later this year.

The most recent publications about this new therapy can be found in Diabetes, May 26, 2006, Nature, June 2, 2005, and Nature Biotechnology, June 2005. The research was funded by Sangamo Biosciences Inc.

DATE: May 19, 2006

Biomechanics practitioners understand all too well that diabetes claims a limb every 30 seconds (according to the Nov. 14, 2005 issue of The Lancet). And while there are volumes of research into wound and ulcer healing, clinicians are beginning to understand more about the mechanisms that cause ulcers in the first place. That knowledge may help them design such interventions as casting and footwear more precisely to prevent foot ulcers or help them heal faster. Researchers agree that diabetic patients have increased joint stiffness and reduced joint mobility, especially in the ankle joint. Several studies have found increased plantar loading in diabetic patients, which seems to increase the risk of plantar ulcers.

A study by researchers in the internal medicine department at Tor Vergata University of Rome, published in Diabetic Medicine in December, found that mobility of the first metatarsophalangeal joint was significantly reduced in diabetic patients, both those with and without neuropathy. That study also found the plantar fascia and Achilles tendon were significantly thickened in diabetic patients both with and without neuropathy compared with a control group. The authors theorized that this thickening may contribute to the windlass mechanism, which enables stiffening of the foot during normal gait, beginning early and continuing throughout gait. "We are convinced that thickening of the plantar fascia and Achilles tendon does contribute to early appearance of the windlass mechanism. Consequently, the foot becomes rigid and very poorly adaptable in its interaction with the floor," said Luigi Uccioli, professor of medicine at Tor Vergata and one of the study's coauthors.

A University of Iowa study, to be published in Gait & Posture and available now online, found that greater stiffness of the heel and ankle at rest didn't necessarily mean more stiffness during gait. The Iowa researchers found a reduced passive range of motion at the ankle and increased stiffness at rest among diabetic patients. However, the ankle motion, stiffness, and plantar pressure of the diabetic patients were similar to those of a control group during walking at the same speed. The diabetic patients in the Iowa study were using strategies such as reduced push-off and shortened stride length to compensate for their stiffness at rest, said Smita Rao, a graduate student in the orthopedic gait analysis laboratory at Iowa and the study's lead author. In spite of these strategies, the diabetic patients sustained plantar loads similar to those of the control subjects. This suggests other factors may render diabetic patients vulnerable to increased plantar loading, and these factors may be intrinsic to the foot, Rao said. Rao's paper is part of her dissertation research, which is continuing in a new study of segmental foot mobility in diabetic patients. Her team has found that sagittal motion of the first metatarsal and forefoot and frontal motion of the calcaneus were associated with increased plantar loading under the respective segments in diabetic patients. These findings, still unpublished, may provide more insight into the mechanisms that cause increased plantar loading in diabetic patients.

The Rome study found diabetic patients had increased loading times and force integrals under the metatarsals compared with non-diabetic controls. But the Iowa study found no difference between diabetic and non-diabetic patients. Rao attributes this discrepancy to the fact that the patients in her study wore their customary footwear, whereas the Rome patients were barefoot. Footwear affords a more even distribution of load on the plantar foot and may also facilitate forward transfer of body weight, she said. Another recent study, published in March in Clinical Biomechanics, found peak plantar pressures in the surviving foot among diabetic patients with a transtibial amputation were higher than in diabetic patients without amputation. The researchers found the amputees had shorter strides and a slower gait and walked less per day. They theorized that changes in gait and level of walking activity may affect plantar pressure in the surviving foot and increase the risk of a second amputation.

Reduced plantar loading, reduced risk

All of the above research adds up to one conclusion: The more plantar loads are reduced in diabetic patients, the better their chances for avoiding amputation. In addition to antibiotics and wound healing therapies, Uccioli suggests surgery to lengthen the Achilles tendon as a successful intervention for some ulcers, and Rao cites botulinum toxin injections and silicone implants. But orthotic interventions, including stockings, bracing, footwear, and casts, are also available. Recent research has shown that each of these approaches can be effective. A team of investigators at Twenteborg Hospital in Almelo, the Netherlands compared the offloading effects of four different devices: a custom-molded insole shoe, a fiberglass-cast MABAL shoe (a combination cast and shoe, whose name is an acronym for the inventor and place of invention), a prefabricated pneumatic walking brace, and a bivalved total contact cast. The Twenteborg researchers, who published their findings in the Nov-Dec issue of Wound Repair and Regeneration, found that all four approaches achieved significant reduction in forefoot and heel plantar pressures compared with a control shoe. The total contact cast attained the greatest degree of plantar pressure reduction, followed by the walking brace; the MABAL shoe achieved less reduction, and the insole the least. The authors note that it's unclear how much plantar offloading is necessary to treat diabetic ulcers.

The only drawback of these interventions is that plantar pressures in the midfoot region were increased with all four, leading the researchers to theorize that they transfer loads to the midfoot region. This may be a problem particularly for patients with Charcot foot, said Robert van Deursen, one of the study's coauthors and the director of physiotherapy at the Research Centre for Clinical Kinesiology at Cardiff University, in Wales, U.K. A frequent result of Charcot foot, midfoot collapse increases pressures there, which also increases the risk of ulceration. But for patients without Charcot foot, midfoot plantar pressures are generally low compared to the heel and forefoot, and-even after reduction in forefoot and heel pressures-the increased midfoot pressure isn't as great as in those areas. The bivalved total contact cast does seem to provide the greatest amount of plantar offloading, but some research shows that the TCC reduces patients' activity levels significantly, van Deursen said. Also, the specialized expertise of TCC casting may not be available in some parts of the world. Preventive foot care socks succeeded in reducing plantar foot pressures in patients with diabetic neuropathy in a study published in the August issue of Diabetes Care. Investigators at Withington Hospital in Manchester, U.K., found the socks increased maximum foot contact area by 7.9% and reduced total foot pressure by 9%. Forefoot pressure was reduced 10.2%, with a 14.2% increase in contact area. There's not enough information yet to know how much pressure reduction is needed to prevent diabetic ulcers, according to the study's author, Adam Garrow, a research fellow with the diabetes foot clinic at Withington Hospital. "There is a general consensus that rest and such devices as the total contact cast are the best treatments for plantar foot ulcers," he said.

Another team of Twenteborg researchers tested four forefoot-offloading shoes, plus the MABAL shoe on diabetic neuropathic patients and presented their results at the XXth Congress of the International Society of Biomechanics/29th Annual Meeting of the American Society of Biomechanics, in August. They found the Thanner Cabrio, the Rattenhuber Talus, the Fior & Gentz Hannover, and the Pullman shoe were all equally effective at offloading the forefoot of the diabetic subjects. All four shoes achieved greater reduction than the MABAL shoe, but the Fior & Gentz product was too uncomfortable to be used as a therapeutic shoe. The Twenteborg researchers are studying the effectiveness of this kind of shoe at healing neuropathic plantar forefoot ulcers, according to lead author Sicco Bus, a professor of rehabilitation at the University of Amsterdam. The researchers also plan to study the effects of the forefoot-offloading shoe on the patients' gait in the future, Bus said. Footwear and casting can both be part of a clinical intervention to treat diabetic ulcers, Rao said. "While there is no consensus yet about the most effective footwear, there are exciting new developments in custom footwear design for individuals with diabetes," she said. She cites a study by researchers at the Cleveland Clinic who found that measurements of peak pressure si