Author: Staff Writers

New research shows that neither intake of vitamin D nor circulating levels of 25(OH)D are associated with increased risk of islet autoimmunity (IA) or the development of Type 1 diabetes in young children. The findings appear to be at odds with earlier research, which contradicted the conclusions of the study. The study was published in the journal Diabetologia.

The study involved 198 children who had developed islet autoimmunity among an original group of 2,644 children in the U.S. Researchers regularly measured both vitamin D intake and 25(OH)D levels in the children. 128 of the children had been diagnosed with plasma 25(OH)D levels in a check-up at nine months of age.

Neither vitamin D intake nor 25(OH)D levels were shown to be associated with an increased risk of islet autoimmunity, even after adjusting for confounding factors such as Type 1 diabetes, DQB1*0302 genotype, ethnicity, and HLA-DR3/4.

Researchers measured the antibodies present in the children at the ages of nine, 15, and 24 months. They measured vitamin D intake through parent questionnaires that inquired about the frequency of eating certain foods until the children were nine years old; at 10, the researchers obtained the information from the children directly.

The research team acknowledged that the findings of the study were “somewhat contradictory” to previous research on the subject, which suggested that supplementing the diet of infants with vitamin D could offer a protective effect against Type 1 diabetes.

“Our study, which uses a powerful combination of prospectively collected reports of vitamin D intake and a biomarker of vitamin D status, does not support an association between a child’s usual vitamin D intake or 25(OH)D levels… and the risk of IA (islet autoimmunity) or progression to type I diabetes,” said the research team.

They noted that they still needed to test the actual effects of vitamin D supplements during infancy — whether low intake of vitamin D was harmful or very high intake was beneficial.

Earlier this year, Anastassios Pittas, M.D., with Tufts Medical Center in Boston, presented research findings at the annual meeting of the American Diabetes Association suggesting that higher levels of vitamin D in the blood were associated with a reduced risk of developing Type 2 diabetes. However, the study does not prove a cause-effect relationship, simply a correlation. Though the findings are not enough to provide a direct causal relationship, Dr. Pittas stated that if the findings were confirmed, “…there are huge implications because vitamin D is easy and inexpensive.”

Similarly, a study presented in 2010 at the annual meeting of the Endocrine Society by Dr. Esther Krug, M.D., appeared to show that vitamin D deficiency could be a risk factor for glucose intolerance and that such deficiencies are commonly noted in people with poor diabetes control. Again, the study did not prove a cause and effect relationship between vitamin D levels and diabetes, but it suggested a correlation. As vitamin D deficiencies became more pronounced in the study participants, their diabetes control worsened.

Vitamin D is naturally present in very few foods. Some foods are fortified with vitamin D while many people take dietary supplements. It is also produced when sunlight hits the skin, which begins the vitamin D synthesis process. Vitamin D is important for calcium absorption; it is necessary for bone growth and bone remodeling, and without the vitamin, bones can become weak and brittle. Vitamin D thus helps older adults prevent osteoporosis in addition to its many roles throughout the body.

Amelia Lily, the 16-year-old Lady Gaga fan who performs on the British television talent show X-Factor, seems bound for stardom. She recently gave a performance of Janis Joplin’s Piece of My Heart which had one judge saying, “That was amazing. You blew up the stage.” The judge added, “People work their whole lives and take forever to get to the level that you are at now, you’ve come on that stage so much older than your years.” X Factor is a singing talent show created by Simon Cowell, who also created American Idol.

Few of her fans know, however, that Lily suffers from Type 1 diabetes and was diagnosed with the disease when she only three years old. Now 16, Lily gives herself insulin injections four times a day. Lily’s greatest fear is that her diabetes could affect her while she’s performing: “I have to monitor my blood constantly. It is hard and singing is tiring.” She’s determined not to let the disease affect her career, however: “But I’ve got it, so I’ve just got to deal with it.” She uses carbohydrate-rich foods to ensure that her blood glucose levels don’t drop too severely when she’s performing: “I make sure I have carbohydrates and bananas so my blood sugar is a bit higher than normal because singing uses a lot of energy.” Lily is from Middlesbrough, a large town of about 139,000 in North East England.

Type 1 diabetes is a chronic form of the disease, commonly diagnosed in early childhood or adolescence. In Type 1 diabetics, the immune system attacks the beta cells of the pancreas, which are responsible for producing insulin that transports glucose into cells to be used as energy. When the beta cells die and stop producing insulin, the glucose remains in the bloodstream and the body is unable to use it as energy; this causes the symptoms related to Type 1 diabetes, fatigue, including reduced vision, increased hunger and thirst, and increased urination frequency.

Those living with Type 1 diabetes must use supplementary insulin since their bodies do not produce it on their own, and insulin is necessary for sugar to leave the bloodstream and to be used for energy by cells. Most Type 1 diabetics give themselves insulin injections throughout the day while others use a pump that monitors blood glucose levels and continuously delivers insulin when it is needed. Most Type 1 diabetics take one to four insulin shots every day.

Additionally, people with diabetes must monitor their blood glucose levels to ensure that they do not enter dangerous territory. Blood glucose testing is usually done by pricking one’s finger with a needle called a lancet to produce a small amount of blood that is tested for glucose content. It typically takes less than a minute to receive the results of test. In addition to checking their blood sugar regularly, diabetics must take care when eating and exercising; those activities should be performed at about the same times every day to ensure that blood sugar does not rise or fall too significantly.

Living with diabetes can cause a wide range of complications, from loss of eyesight to cardiovascular disease to nerve damage and amputation of limbs. It is estimated that 5-10% of all diabetes cases are Type 1 diabetes, accounting for about 11 to 22 million people around the world. The rate of Type 1 diabetes has been increasing by about 3% per year.

Sensors for Medicine and Science announced that its implanted continuous glucose sensor, which the company is currently developing, has demonstrated highly accurate results. The sensor tracked glucose levels in study participants with a 77.6% accuracy in the A zone of the Clark Error Grid and a 19.2% in the B zone of the grid, resulting in a mean absolute difference of 12.2%. It is the first time an implant-based sensor has achieved such accuracy. The study also achieved the goal of continuous sensor use in patients for over six months.

“We are pleased to report these findings as a first step to realizing a viable long-life implanted sensor to help millions of people with diabetes manage their glucose better,” Tim Goodnow, Ph.D., president and CEO of Sensors for Medicine and Science. “While still early, the pilot study showed comparable performance as current continuous glucose devices.”

The data gathered by the researchers will be presented in Lisbon, Portugal on September 16, 2011, at the meeting of the European Association for the Study of Diabetes.

The new system is comprised of a reader and a sensor, which is implanted in the subcutaneous area of the patient’s wrist. The sensor is powered by inductive currents and is remotely interrogated; it doesn’t require a battery to function and isn’t even wired to the reader, which is a wristwatch-like device that displays blood glucose levels. Once it is implanted, the sensor functions continuously and automatically.

The study involved nine subjects who had Type 1 diabetes. The participants were implanted with a sensor in each wrist for about 29 days; researchers analyzed about 3,000 results from the sensors and compared them with YSI blood glucose levels. Using the Clarke Error Grid, or CEG analysis, the researchers demonstrated that 96.8% of the readings fell into zones A or B of the grid, which is used to measure differences between lab references and glucose monitoring devices. The grid is divided into five zones, labeled A, B, C, D, and E. Results in zone A are considered very accurate while results in zone B are clinically acceptable; C, D, and E results are less accurate.

“Based on the promising results obtained, we plan to initiate more clinical trials in the very near future, including pursuing collaboration on artificial pancreas research,” says Goodnow.
Sensors for Medicine and Science is focused on developing chemical sensing technologies that help monitor the presence of important compounds in the body, such as glucose for diabetics. The sensor is smaller than a penny; it automatically measures glucose levels every few minutes without requiring any input from the patient and communicates the data wirelessly to the external wristwatch receiver. SMSI hopes that patients will use the device for 6-12 months, after which it will be replaced to ensure proper functioning.

One of the primary motivators for SMSI’s development of an automatic, non-invasive glucose monitoring solutions is the lack of proper monitoring in diabetics; the company cites that on average, diabetics check their blood sugar less than twice a day. According to SMSI, the pain and inconvenience of the finger prick test discourages diabetics from checking their blood glucose frequently; a non-invasive monitoring device would help diabetics monitor their blood glucose more closely.

Additionally, SMSI states that standard glucose measuring can be complex and cumbersome, often leading to patient error of up to 15-20% in actual blood glucose levels, partly from user error. An implanted glucose sensor would sidestep many of the complications that surround glucose monitoring today.

Researchers in Jerusalem have identified a possible cure for Type 1 diabetes in the form of a signal that activates regeneration of pancreatic beta cells, which are responsible for producing insulin. The research team claims that the discovery could pave the way for treating Type 1 diabetes by restoring or increasing pancreatic beta cell function.

The study, which took place over a period of several years, was led by Professor Yuval Dor with the Hebrew University of Jersualem Institute for Medical Research Israel-Canada. Also working on the project were researchers with the Hadassah University Medical Center, and Roche, a research-focused pharmaceuticals company. The study was funded by the Juvenile Diabetes Research Foundation.

“Our work shows that as the glucose level is increased in the blood, it tells the beta cells to regenerate,” said Professor Dor. “It’s not blood glucose per se that is the signal, but the glucose-sensing capacity of the beta cell that’s the key for regeneration.”

The research shows for the first time that high glucose levels in the blood are a trigger that initiates the regeneration of pancreatic beta cells. These cells are attacked by the immune systems of individuals with Type 1 diabetes; the destruction of the cells means that the individual cannot produce as much insulin, resulting in a disruption in the body’s handling of blood glucose. The glucose cannot be absorbed into cells and used for energy, so the patient must receive insulin injections, usually several times a day, to compensate for lowered insulin production. To reverse the effects of Type 1 diabetes, the pancreatic beta cells need to be regenerated and enlarged.

The research team used diabetic mice to study the effects of elevated blood glucose levels on individuals with Type 1 diabetes. They found that diabetic mice with elevated blood glucose levels had regenerated more beta cells than did the mice without diabetes, which seems to suggest that glucose is a key component in the regeneration of beta cells. The research also showed that glucokinase, an enzyme that senses the presence of glucose, is an important compound in activating the beta cell regeneration process.

“This means that the more work that beta cells are required to do, the more of themselves they make,” said Shay Porat, a graduate student who spearheaded the study along with Noa Weinberg, another student. As existing beta cells found it more difficult to keep up with their work load, they initiated the regeneration of more beta cells.

As the study demonstrated the central role that glucokinase plays in beta cell regrowth, it could pave the way for therapeutics that manage the levels of that enzyme and encourage existing beta cells to replicate.

Even more exciting, the research could lead to therapies that prevent the immune system from destroying the beta cells in the first place, which would constitute a cure for Type 1 diabetes.

According to Professor Aaron Hanukoglu with Tel Aviv University’s Sackler Medical School, “The incidence of Type 1 has been rising persistently for several decades in many countries around the world including Israel, and many research groups are trying to find a cure or prevention for this chronic disease. This Jerusalem research on mice is very elegant and laborious, and if proven true in humans, it may lead to development of therapeutic measures for regeneration of pancreatic beta cells and a cure to juvenile-onset diabetes.”

The Screen Actors Guild is awarding Mary Tyler Moore, known for her roles in 60s and 70s television with “The Dick Van Dyke Show” and “The Mary Tyler Moore Show” as well as her work in promoting diabetes research, with the lifetime achievement award.

Moore, now 74, also works as a producer and has suffered from Type 1 diabetes herself. The Screen Actors Guild announced that Moore will be presented with the lifetime achievement award in at its yearly television and film awards ceremony in January 2012. Moore has won seven Emmys for her roles in television. She was also nominated for an Oscar for her role in the 1980 film “Ordinary People.”

Moore’s big break came when she was cast as Laura Petrie, wife of Dick Van Dyke in the 60s sitcom named after him. She was 23 at the time. Moore later produced and starred in “The Mary Tyler Moore Show,” playing a single career woman working at a news station.

“Mary Tyler Moore won our hearts as Laura Petrie and Mary Richards, our respect as her production company became synonymous with quality television, our awe as she tackled difficult subject matter in film and on Broadway, and our admiration she turned her public recognition into a catalyst to draw attention to critical and deeply personal health and social issues,” said Ken Howard, national president of the Screen Actors Guild. The Guild represents over 125,000 actors working across film, television, commercials, and video games. Moore will be presented with the award on January 29, when the Guild will also honor the best performances in film and television at their annual awards ceremony.

At the age of 33, around the time she was working on “The Mary Tyler Moore Show,” Moore was diagnosed with Type 1 diabetes. “When the doctor said I had diabetes, I conjured images of languishing on a chaise longue nibbling chocolates,” she said of her initial diagnosis. “I have no idea why I thought this.” Moore quickly learned that living with diabetes meant managing insulin levels with injections and finger prick tests.

Although she admits that having Type 1 diabetes limits spontaneity, Moore still uses insulin injections and refuses to use a pump that automatically administers insulin. She admits that planning is important with this approach to living with diabetes: “You’ve got to always plan. It is a fact of life that if someone invites you out to dinner you have to think, ‘What are they going to be doing when they serve you dinner? How quickly are they going to get it on the table from the time I arrive? When should I take my shot? What should I eat of what’s available?'”

Moore says that she carries a syringe loaded with insulin wherever she goes; if her insulin levels drop too low, she isn’t squeamish about giving herself a shot. She does say that she’s impressed by how well the younger generations approach handling diabetes — much better than she did when she was younger.

Moore was named as the international chairwoman of the Juvenile Diabetes Research Fund and has used her position to raise funds for research and to promote diabetes awareness. In honor of Moore’s efforts with the JDRF, the organization established a research initiative called “Forever Moore,” which supports the Fund’s Academic Research and Development and its Clinical Development Program. The program works toward developing new therapies for Type 1 diabetics from research into diabetes.

A recent study has found that insulin pump therapy may be more cost effective than frequent daily insulin injections in Type 2 diabetics who require large doses of insulin throughout the day.

According to Phyllis Wolff-McDonagh, DNP, a certified diabetes instructor, pump therapy was less expensive over the long term because the insulin was absorbed more efficiently than with injections. Wolff-McDonagh presented the findings at the annual American Association of Diabetes Educators meeting; the study analyzed results from Type 2 diabetics with heavy insulin requirements, over 150 units per day. In those patients, insulin pumps saved over $12,000 in a four year period.

Type 1 diabetics have long used insulin pumps to supplement their bodies’ insulin deficiencies. Few studies have been conducted on the efficacy of insulin pumps for Type 2 diabetics; however, the existing research shows that they appear to be at least as effective in regulating hemoglobin A1c levels as multiple daily insulin injections; in some cases, insulin pumps have actually been more effective. None of the previous research has considered the cost of injections versus the cost of pumps.

In Wolff-McDonagh’s new study, the researchers studied medical records of 15 adults who ranged in age from 40 to 64. All of the patients had begun using insulin pumps within the seven years prior to the study; all had failed to achieve HbA1c levels under 8% even though they had undertaken multiple insulin injections every day for at least a year.

The results of the study showed that the mean HbA1c level in the participants dropped from 9.4% at the beginning of the study to 8.2% after one year. The participants showed an average increase in body mass index from 38.6kg/m2 at the beginning of the study to 40kg/m2 after one year. Previous research into both Type 1 and Type 2 diabetes have shown similar increases in body weight associated with improved blood glucose regulation; the weight gain is thought to be associated with a reduction in glycosuria, or the excretion of glucose in the urine.

To analyze the cost of using the pumps, the study participants were separated into three groups according to their level of basal insulin use through multiple daily injections; the low-insulin group used less than 100 units per day, the moderate group used 100-150 units per day, and the heavy-insulin group used over 150 units per day. In calculating costs, the researchers took into account the cost of insulin and supplies such as syringes and pumps.

For patients who received four injections per day, the cost was $525 per year, or $2,100 for four years. The cost of pump therapy included $5,250 for the pump plus $1,500 per year for pump supplies, equaling $11,250 over a four year period.

The cost efficiency of pump therapy varied according to the dosage of the patients. For low-dose patients, injections were less expensive than pumps, with the former costing $9,172 for four years versus $14,994 for the latter. For moderate insulin users, the costs were about the same at $22,380 for injections and $23,002 for pump therapy. For heavy insulin users, pumps were much less expensive at $28,826 versus $41,100 for injections. Dr. Wolff-McDonagh added that since insulin pumps afford more efficient glycemic control, they may also ultimately be cheaper for moderate insulin users.

Pump therapy is not popular among Type 2 diabetics because reimbursement is uncommon. To determine eligibility for receiving a pump, Medicare looks at C-peptide levels, which Wolff-McDonagh believes should change: “Medicare needs to re-look at this, but before that can happen, large randomized controlled studies need to be done to see what happens over long periods of time,” she said.

Today, almost 26 million Americans — adults and children — have been diagnosed with diabetes. By 2025, that number is projected to rise to 438 million individuals around the world, which would be about 7.8% of the world’s adult population. Combating the rise of diabetes involves multifaceted strategies but promoting a healthy diet is one of the most effective ways of reducing the numbers of the disease. Two recent studies have shown that a common food source can aid in the fight against diabetes, suggesting that including almonds in the diet of a Type 2 diabetic can help to regulate blood sugar and cholesterol levels.

The first study, published in the journal Metabolism, discovered that study participants, who had Type 2 diabetes, had a 30% decrease in their blood glucose levels after consuming a meal high in carbohydrates when they ate an ounce of almonds immediately before the meal. Those who did not have Type 2 diabetes showed a 7% decrease in blood glucose levels when they consumed the same amount of almonds and ate the same meal. The participants also fasted overnight and were then separated into two random groups; one group received a meal without almonds and the other group received a meal that included almonds. Among the Type 2 diabetics in the group that received the meal with almonds, blood sugar levels were shown to be reduced after the meal.

A second, smaller pilot study was conducted with some of the same participants to determine whether regular almond consumption had an effect on blood sugar levels. Participants with Type 2 diabetes were randomly separated into two groups of six to seven subjects; one group ate an ounce of almonds five days a week for 12 weeks. The other group ate two cheese sticks at the same frequency and for the same time period. The almonds and cheese sticks were similar in nutritional properties: the almonds contained 163 calories, 0g carbohydrates, and 14g fat, while the cheese sticks had 160 calories, 0g carbohydrates, and 12g of fat. Other than the almonds and cheese sticks, the two groups ate a very similar diet.

The study found that the group who regularly consumed almonds showed a 4% decrease in levels of hemoglobin A1c (HbA1c), which is a measure of blood sugar levels. They also showed a 4% reduction in body mass index, or BMI, over the group that ate cheese sticks for the period of the study.

Another study published in the journal Diabetes Care discovered that nuts (such as almonds) helped Type 2 diabetics in maintaining healthy cholesterol and blood sugar levels in men and postmenopausal women.

“Both of these studies further deepen our understanding of the benefits of almond consumption for those with Type 2 diabetes,” said Karen Lapsley, Ph.D. “Those with diabetes are faced with many challenges with their disease management, which is why we are always energized when new research is published that supports our understanding of almonds’ role in helping alleviate some of the difficulties.” Lapsley is also the Chief Science Officer for the Almond Board of California.

A one-ounce serving of almonds offers 3.5 grams of fiber, 13 grams of unsaturated fat and only 1 gram of saturated fat. The studies demonstrate that almonds make a healthy food choice for Type 2 diabetics, helping them to maintain blood glucose levels. The studies show that consumption of almonds provides benefits for Type 2 diabetics both in the long and short term, making them an excellent choice for anyone coping with diabetes.

A study that analyzed over 3,400 French adults over a period of 14 years found that those with Type 2 diabetes who received insulin treatment had a significantly increased risk of death.

According to Dr. Emilie Bérard, an epidemiology researcher at the University Hospital Center in Toulouse, France, patients with diabetes who were “treated with insulin at baseline were at increased risk of all-cause mortality.” Dr. Bérard spoke at the yearly meeting of the European Society of Cardiology, adding that the data “provides further information to the debate on the risks and benefits of increasing hypoglycemic treatments.”

The study adjusted for factors that may have affected the outcomes of the data. Even after the adjustments were made, the study found that diabetics who received treatment with insulin were five times more likely to die over the 14 year period of the study than the study participants who did not have diabetes. Those who received insulin were also 1.5 to 2.2 times more likely to die than diabetics who were treated with other hypoglycemic drugs such as metformin or sulfonylurea. The relative risk of death for diabetic patients who were treated with insulin was nearly double that of diabetic patients who did not recieve any treatment at all — the latter group was about 2.8 times more likely to suffer death than patients without diabetes.

Dr. Lars Rydén, a professor of medicine at the Uppsala University in Sweden, cautioned against taking the study’s findings at face value. The study was “on the right track,” according to Dr. Rydén, but its findings must also “be taken with a grain of salt.”

“The results indicate something, but we need further studies,” continued Dr. Rydén. He commented that a major potential flaw in Dr. Bérard’s findings were that it used several adjusting factors in a fairly small sample group of only 171 diabetic patients. “I think [the analysis] is on the edge of controlling for too many things in a small number of people, which led to extremely wide confidence intervals,” said Dr. Rydén.

The findings were also questioned because the participants did not undergo an evaluation of their A1c levels when the study began in 1995 and 1996. According to Dr. Bérard, this means that the adjusted analysis could not account for the varying quality of diabetes control that the patients may have received at baseline. Dr. Bérard speculated that the insulin treatment could have caused a higher rate of hypoglycemia which lead to a higher mortality rate, it could have caused increased weight gain, or it could be indicative of more serious cases of diabetes. It may have also stimulated the sympathetic nervous system, which could have promoted atherosclerosis and triggered vasoconstriction.

The study analyzed data collected from a random sample of 3,403 French adults who were aged between 34 and 64. The study began in 1995 and 1996 and was a part of the MONICA (Multinational Monitoring of Trends and Developments in Cardiovascular Disease) project, a large study sponsored by the World Health Organization. Of the study sample group, 171 participants had diabetes, with 123 on a hypoglycemic regimen and 48 who were not being treated for diabetes at all.

Dr. Bérard’s team analyzed the participants’ data 14 years after their first assessment and found that the mortality rates varied widely, from 7% in the group without diabetes to 33% in the group who were treated with insulin; those who were not receiving hypoglycemic treatment at the beginning of the study had a 23% mortality rate.

For decades, scientists have been trying to identify the molecules that activate beta cell growth in the fight against diabetes. Once these molecules are identified, scientists could develop therapeutics that target them. One research team, funded by the Juvenile Diabetes Research Fund in collaboration with pharmaceutical manufacturer Hoffman-La Roche, recently made significant headway in this area of diabetes research by discovering a protein responsible for beta cell growth as well as a compound that activates it. The team’s findings were published in the journal Cell Metabolism.

The research team was led by Markus Stoffel, M.D., Ph.D., professor at the Swiss Federal Institute of Technology in Zurich, Switzerland a recipient of the Juvenile Diabetes Research Fund’s Gerold & Kayla Grodsky Basic Research Scientist Award. The team is hopeful that its findings will prove to be significant progress in the effort to develop new therapeutics that can be used to regenerate beta cells.

The team’s findings build on research that they conducted five years ago. In that previous research, Dr. Stoffel’s team discovered that a protein known as Tmem27 is found on the surface membranes of beta cells — the insulin-producing cells located in the islets of Langerhans in the pancreas. They found that higher concentrations of Tmem27 on beta cells were linked to increased mass of the islets of Langerhans in mice. Additionally, they discovered that cleaving Tmem27 leaves it totally inactive.

“We hypothesized that if we could prevent Tmem27 from being cleaved and increase the levels of this protein, we could get more beta cell growth,” said Dr. Stoffel. “This observation gave us the rationale to look for what was inactivating Tmem27.”

Once Dr. Stoffel’s team discovered that cleaving Tmem27 de-activated it, they set about searching for molecules that could be responsible for the process. They zeroed in on Bace2, an enzyme protein that can also be found on the surface membrane (or plasma membrane) of beta cells. To confirm their theories, the team analyzed mice and found that those with lower levels of Bace2 had larger islets and a greater number of beta cells in the pancreas through the process of cell regeneration, or proliferation. The mice with lowered levels of Bace2 were also more efficient at removing glucose from the bloodstream than were the mice that had Bace2.

The team’s next goal was to demonstrate the growth of beta cells by inhibiting Bace2. They worked with the scientists of therapeutic company Hoffman-La Roche, who developed an inhibiting compound that prevented Bace2 activity. When the mice were given the compound, their Bace2 was inhibited and their beta cells began to regenerate. Additionally, it was discovered that Bace1, a chemically similar compound to Bace2, does not cleave the Tmem27 protein. Bace1 may be linked to a variety of other diseases, including Alzheimer’s disease and Down syndrome, but since it does not cleave Tmem27, the door is open for anti-diabetes therapeutics that inhibit Bace2 specifically. Research to develop inhibitors for Bace1 is already underway by several companies.

In addition to the identification of a possible target for anti-diabetes therapeutics, the research that Dr. Stoffel’s team conducted may also pave the way for the development of new tests to determine the presence of Tmem27 fragments in the bloodstream, which could be used as a measure of the number of beta cells present in the pancreas.

A joint study conducted by the Scripps Research Institute and the Dana-Farber Cancer Institute at Harvard University has discovered a new type of anti-diabetic therapeutic that works by targeting a particular molecular switch.

The findings set the stage for the development of new anti-diabetic therapeutics that will have drastically reduced adverse side effects compared to current anti-diabetics such as Avandia (rosiglitazone), which will be discontinued from sale this fall amid concerns that it increases the risk of heart attack.

The results of the new study were published in the journal Nature. It describes a newly-discovered compound called SR1664 and was led by Patrick R. Griffin with the Department of Molecular Therapeutics at Scripps Florida, Theodore Kamenecka, the associate scientific director of medicinal chemistry at Scripps Florid, and Bruce Spiegelman, a professor of cell biology at Dana-Farber Cancer Institute.

“In this study, we demonstrate that we have discovered novel compounds that work effectively through a unique mechanism of action on a well-validated clinical target for diabetes,” stated Griffin. “This unique mechanism of action appears to significantly limit side effects associated with marketed drugs. This study is a great example of interdisciplinary, inter-institutional collaboration with chemistry, biochemistry, structural biology, and pharmacology.”

“It appears that we may have an opportunity to develop entire new classes of drugs for diabetes and perhaps other metabolic disorders,” says Spiegelman.

The study is a follow-up on research that the authors published last year in the same journal, Nature. That research suggested that the development of insulin resistance in humans could be caused by a mechanism linked to obesity. The research found that a protein called PPARG affects the normal function of several genes when it undergoes phosphorylation, or the addition of a phosphate group to the protein. The kinase Cdk5, an enzyme involved in multiple sensory pathways, is responsible for causing the phosphorylation of PPARG.

The researchers’ new study confirms what they suspected in their original research: blocking Cdk5 from acting on PPARG could be the basis of effective anti-diabetes therapies. The SR1664 compound discovered in the newer research binds to PPARG but does not activate the transcription of genes.

Griffin’s team is cautious about being overly optimistic in their report on the side effects of anti-diabetes treatment with SR1664. However, the research did clearly demonstrate that this type of treatment causes fewer side effects in mice than medications such as Avandia, which can cause weight gain or increased plasma volume.

In the study, the researchers treated diabetic mice with both Avandia and with SR1664. While both groups showed improved blood glucose levels, the mice treated with Avandia also displayed more fluid retention and weight gain soon after beginning treatment. The mice treated with SR1664, on the other hand, showed neither. The researchers also tested SR1664 in cell cultures for its effect on bone formation and fat generation in bone cells, both side effects of Avandia and other therapies. SR1664 caused no such side effects.

Although SR1664 will likely not be used directly as a drug, its discovery will allow researchers to develop similar compounds that can be used to treat diabetes. “With data in hand showing that our compounds are as efficacious as the currently marketed PPARG modulators, while demonstrating a significant improvement of side effects in limited studies, we are now advancing newer compounds with improved pharmaceutical properties into additional studies,” says Griffin.