The results, reported online in The Proceedings of the National Academy of Sciences, push scientists a step closer to finding ways to treat this condition.

"Now that we've isolated dendritic cells from the pancreas, we can look at why they get into the pancreas and determine which of the materials that they pick up are most critical to causing this form of diabetes," says senior author Emil R. Unanue, M.D., the Paul and Ellen Lacy Professor of Pathology. "That may allow us to find ways to inhibit dendritic cell function in order to block the disorder."

The American Diabetes Association estimates that 1 million to 2 million Americans suffer from type 1 diabetes, which is also called juvenile diabetes because it frequently develops in children.

Patients require insulin injections to survive because the immune system has destroyed the islets of Langerhans, which contain the body's only beta cells. The insulin these cells make is required for the critical task of regulating blood sugar levels.

Scientists detected dendritic cells in the islets years ago. Dendritic and other antigen-presenting cells are the sentinels of the immune system: They pick up bits of protein from around the body and present them to lymphocytes to initiate an immune system reaction. The lymphocytes lead immune attacks against foreign invaders like bacteria and viruses and eliminate them, clearing infections. But when interaction between an antigen-presenting cell and a lymphocyte leads to a part of the body being mistakenly identified as alien, the resulting attack harms the body, causing autoimmune diseases.

Although dendritic cells' presence in the islets and their ability to summon immune attacks made them likely suspects in type 1 diabetes, they were challenging to isolate from the pancreas for closer examination.

"They're very tiny and there are only about 5 to 10 of them per islet, each of which contains approximately a thousand cells," explains Unanue. "So the senior postdoctoral researcher in the lab who did this work, Boris Calderon, had to develop some sophisticated cellular assays to pick them up."

Calderon, M.D., found indications that the cells were carrying granules of insulin and pieces of proteins from beta cells on their cell surfaces. To test whether this cargo carried by the dendritic cells had the potential to trigger an immune attack on beta cells, Calderon exposed the dendritic cells to lymphocytes taken from diabetic mice. The lymphocytes were activated by the dendritic cells of the islets and switched into attack mode.

In a separate line of research, Unanue's lab has learned that dendritic cells in the pancreas may normally have beneficial effects on the health of beta cells. They've shown that when dendritic cells are absent from the pancreas, the beta cells are smaller, an indication that they're not as healthy.

"We think these dendritic cells aren't in the pancreas by accident," says Unanue. "We believe that in the normal individual they help maintain the health of beta cells. But in a person with autoimmune diabetes, they appear to start the problems that destroy beta cells."

The key distinction likely lies in a group of proteins called the major histocompatibility complex (MHC). Two decades ago, Unanue and Paul Allen, Ph.D., the Robert L. Kroc Professor of Pathology and Immunology, showed that the MHC provides the stage on which antigen-presenting cells show bits of protein or peptides to other immune system cells. Scientists believe autoimmune conditions like type 1 diabetes are caused by differences in what the MHC binds to and how it presents that material to immune attack cells. In support of this theory, Unanue's laboratory and that of Michael Gross, Ph.D., Washington University professor of chemistry, have collaboratively shown that the genes that encode the MHC proteins in the diabetic mouse are unique and bind to a set of very characteristic peptides.

In addition to studying what protein fragments carried by dendritic cells are essential for causing type 1 diabetes, Unanue and others are working to learn how genetic variations in the MHC alter the chances that the immune system will mistakenly attack the body.

Gregory L. Burke, M.D., M.S., of Wake Forest University School of Medicine, Winston-Salem, N.C., and colleagues assessed data from the Multi-Ethnic Study of Atherosclerosis (MESA), which involved 6,814 individuals age 45 to 84 who did not have cardiovascular disease when the study began (2000 to 2002). Participants completed a standard questionnaire with information about demographics and health risk factors and also underwent testing for a variety of cardiovascular disease markers.

“A large proportion of white, African American and Hispanic participants were overweight (60 percent to 85 percent) and obese (30 percent to 50 percent), while fewer Chinese American participants were overweight (33 percent) or obese (5 percent),” the authors write. “A higher body mass index (BMI) was associated with more adverse levels of blood pressure, lipoproteins [cholesterol] and fasting glucose despite a higher prevalence of pharmacologic treatment.”

Obesity also was associated with the following risk factors for heart disease and stroke:
• A 17 percent greater risk of coronary artery calcium, which may be a marker of coronary artery disease
• A 45 percent greater risk of having artery walls thicker than the 80th percentile in the common carotid arteries, which is a marker for atherosclerosis
• A 2.7-fold greater risk of having a left ventricle (the lower chamber of the heart that pumps blood throughout the body) with a mass higher than the 80th percentile

“These data confirm the epidemic of obesity in most but not all racial and ethnic groups,” the authors conclude. “The observed low prevalence of obesity in Chinese American participants indicates that high rates of obesity should not be considered inevitable. These findings may be viewed as indicators of potential future increases in vascular disease burden and health care costs associated with the obesity epidemic.”
(Arch Intern Med. 2008;168[9]:928-935.

“Arthritis is a frequent co morbid condition for adults with diabetes,” said John H. Klippel, M.D., president and CEO, Arthritis Foundation. “But for both diseases, physical activity is key to effective management. A lack of physical activity actually results in undesirable consequences including increased pain, stiffness, inflammation, physical limitation and potential disability.”

Arthritis is the most common cause of disability in the U.S., affecting one in every five Americans (21 percent). Diabetes affects approximately 7 percent of the American population, with nearly a third unaware that they have the disease.

"Everyone faces the same common barriers to being more physically active, such as lack of time, competing responsibilities, lack of motivation and difficulty finding an enjoyable activity,” said Chad Helmick, M.D., CDC epidemiologist and co-author of the study. “Those who also have arthritis face additional disease-specific barriers, such as concerns about aggravating arthritis pain and causing further joint damage, and knowing which types and amounts of activity are safe for their joints."

The good news is that safe and effective self-management programs are available. People living with arthritis and diabetes can benefit from participating in one of the Arthritis Foundation’s exercise or self-management programs, such as the Arthritis Foundation Aquatic Program, the Arthritis Foundation Exercise Program and the Arthritis Foundation Self-Help Program,” said Klippel. “People should contact their local Arthritis Foundation chapter at www.arthritis.org for information about the resources available in their specific area.”

The Importance of Taking Action

Arthritis currently limits activity for 19 million Americans, taking a $128 billion toll on the U.S. economy annually in direct [medical expenditures] and indirect [lost earnings] costs. With the aging of the Baby Boomer population, the prevalence of arthritis is expected to rise by 40 percent in the next two decades alone.

“Despite evidence of the growing need for intervention to stop the rise of this disabling disease in our population, the level of federal funding for arthritis public health and research has declined steadily by nearly $28 million over the past six years,” said Klippel. “We are on the verge of a public health crisis and must take action now.”

The Arthritis Foundation is working to help address this ever-growing problem through the proposal of legislation. The Arthritis Prevention, Control and Cure Act (S. 626/H.R. 1283) proposes to strengthen arthritis public health initiatives, which would ensure that more people are diagnosed early and avoid pain and permanent disability.

“This new funding will strengthen and revitalize New York’s biomedical research industry and potentially help thousands of New Yorkers who suffer debilitating diseases, including Alzheimer’s, Parkinson’s, diabetes and cancer,” said Governor Paterson who played a leading role in the development and implementation of the state’s stem cell initiative while he was Lieutenant Governor.

The first awards – totaling nearly $15 million – were made to 25 research institutions in January. Those grants focused on increasing the capacity of research institutions in New York State to engage in stem cell research.

New York State Health Commissioner Richard F. Daines, M.D., who serves as Chair of the Empire State Stem Cell Board, said: “The research funded by this initiative offers the promise of new treatments, therapies and even cures for some of the most serious diseases. This funding will also provide an economic stimulus to New York’s biomedical industry at a time when funding from the National Institutes of Health has not kept up with the need.”

Nobel Laureate Harold Varmus, M.D., President of Memorial Sloan Kettering Cancer Center and a member of the Empire State Stem Cell Board, said: “Human embryonic stem cells offer an unprecedented opportunity to study all aspects of human development. Advances in the understanding of fundamental biology will likely take us to unimagined realms of understanding and public health applications.”

The majority of New Yorkers support embryonic stem cell research, as demonstrated by a 2006 Zogby International poll which found that 84 percent of New Yorkers support embryonic stem cell research. Nearly 70 percent of those polled expressed support for state funding as a way of countering President Bush’s policy restricting federal funding to research that only uses human embryonic stem cell lines in existence as of August 9, 2001.

The grants supported by the $109 million are projected to be awarded in October 2008. With this funding, New York's investment in stem cell science will be surpassed only by the state of California, which started its stem cell program four years earlier.

The new RFAs seek proposals to broadly stimulate stem cell research through:

* Consortia Planning Grants-to encourage collaborations among new and established stem cell investigators within and between New York State institutions and in partnership with non-New York State investigators and corporations.
* Facilities and Equipment Grants-to support the establishment and operation of multi-institutional core facilities and specialized equipment to maximize the expertise, efficiency, and quality of stem cell research.
* Investigator-Initiated Research Projects and Innovative, Developmental or Exploratory Activities (IDEA) in Stem Cell Research-to support investigations of stem cell biology that will increase understanding of the unique properties of stem cells and allow their use to treat disease; awards for well developed basic, translational or pre-clinical research, or for preliminary testing of novel or high-risk hypotheses.
* Targeted Investigation of Pluripotent Stem Cells-to support the development of improved methods for deriving pluripotent stem cell lines; defining the reprogramming mechanisms, and comparing the utility of induced pluripotent stem (IPS) cells with embryonic and other pluripotent stem cells for use in disease models and potential therapeutic applications. Induced pluripotent cells, like embryonic cells, have the potential to develop into other types of body tissues.

Letters of intent for all the RFAs are due May 28, 2008, with applications due June 30, 2008. The full Requests for Applications can be found on the state Department of Health’s website (www.nyhealth.gov/funding) and on the NYSTEM website (www.stemcell.ny.gov/research_support.html).

The state's stem cell initiative is administered by the Department of Health through the New York State Stem Cell Science/NYSTEM program under the direction of the Empire State Stem Cell Board. All research funded by the state must adhere to the guidelines of the National Academies for Science (NAS) Guidelines for Human Embryonic Stem Cell Research or those of the International Society for Stem Cell Research (ISSCR). New York’s legislation expressly forbids the use of state funding for human reproductive cloning.

“This points to a new opportunity to find substances made by subcutaneous fat that may actually be good for glucose metabolism,’’ said Dr. Kahn, Head of the Joslin Research Section on Obesity and Hormone Action and the Mary K. Iacocca Professor of Medicine at Harvard Medical School. “If we can identify how subcutaneous fat does this, we will have a big clue as to where to look for these substances.”

Kahn noted that obesity in the abdominal or visceral area -- the classic “beer belly” or “apple” shape -- increases the risk of diabetes and mortality, and said it has been thought that obesity in subcutaneous areas -- the “pear” shape -- might decrease such risks.

“We started out to answer the basic question of whether fat inside the belly is bad for you because of where it is located, or is abdominal fat itself different from fat in other places,” said Kahn, an internationally recognized researcher in diabetes and metabolism.

To test if the differences were due to anatomic location or intrinsic properties of the fat deposits themselves, transplantations were performed in mice. The researchers found that when subcutaneous fat was transplanted into the abdominal area, there was a decrease in body weight, fat mass, glucose and insulin levels and an improvement in insulin sensitivity. By contrast, transplantation of abdominal fat into either the abdominal or subcutaneous area had no effect.

The paper concludes that subcutaneous fat is intrinsically different from visceral fat and may produce substances that can improve glucose metabolism.

“The surprising thing was that it wasn’t where the fat was located,” Kahn said. “It was the kind of fat that was the most important variable. Even more surprising, it wasn’t that abdominal fat was exerting negative effects, but that subcutaneous fat was producing a good effect. Animals with more subcutaneous fat didn’t gain as much weight as they aged, had better insulin sensitivity, lower insulin levels and were improved all around.”

Earlier studies in humans had shown that removal of subcutaneous fat by liposuction does not result in improvement of any aspect of metabolic syndrome, a collection of medical problems related to insulin resistance, but none had focused on possible good effects of this subcutaneous fat. However, one human study did show that obese individuals with high levels of both intra-abdominal and subcutaneous fat were more insulin sensitive than those with only high levels of intra-abdominal fat.

In addition, Kahn noted that a class of diabetes drugs called thiazoladines may cause patients to gain weight in the subcutaneous area, yet also improve insulin sensitivity.

Kahn said it is possible that subcutaneous fat may be producing certain hormones, known as adipokines, which produce beneficial effects on metabolism. These effects may offset the negative effects produced by abdominal fat.

The next step is to identify how subcutaneous fat produces these substances that improve metabolism and then find the substances themselves with the idea of creating a drug that can do the same thing.

“We’re already trying to identify through the use of proteomics what is coming out of the different fat cells,” Kahn said.

That’s just what Tony Means, PhD, and his team at the Duke University Medical Center were able to do when they blocked a brain enzyme, CaMKK2, in mice.

For many years, scientists have been identifying and testing every step of the appetite stimulation and suppression pathways in search of a target. Such research is considered critical to finding ways for people to better control their weight and minimize their risk of developing diabetes, heart disease and other health conditions.

Activation of the enzyme CaMKK2 is just one step in the appetite stimulation pathway located in the hypothalamus section of the brain. An empty stomach releases the hormone ghrelin, which launches a cascade of signals that ultimately results in increased appetite.

Means and colleagues believed that CaMKK2 in the ghrelin pathway might be a likely candidate for study, because it activates AMPK, an enzyme that stimulates animals to eat and gain weight. They tested their theory in several ways, the results of which are published in the May issue of Cell Metabolism. The work was funded by NIH grants, as well as by the Australian Research Council, National Heart Foundation, and the National Health and Medical Research Council of Australia.

First they blocked CaMKK2 in mice with a specialized molecule inhibitor and then measured food intake. These mice ate significantly less food than untreated mice during the six days in which they were evaluated, and also lost body weight, which led the scientists to think they might be on to something.

Next they studied a group of mice that normally do not make CaMKK2 and found that the molecule inhibitor did not change feeding behavior or reduce weight. “The fact that blocking CaMKK2 worked in normal mice to make them eat less and lose weight, but not in mice missing the enzyme, provides compelling evidence that CaMKK2 signaling is a requirement for appetite control,” Means said.

They also studied both normal mice and mice missing CaMKK2 to learn how these types responded to low-fat and high-fat diets. After nearly 30 weeks on the specific diets, the normal mice on the high-fat diet became diabetic – they were unable to respond to insulin and weren’t able to manage blood sugar levels well. In contrast, the normal mice on a low-fat diet stayed healthy.

In mice missing CaMKK2, the scientists found that they stayed healthy regardless of whether they were on a low-fat or high-fat diet. The CAMKK2-negative mice apparently were protected from changes that lead to diabetes in a high-fat diet.

“Remarkably, we find that blocking CaMKK2 in the brain prevents the deposits of fat in liver and skeletal muscle that are characteristic of obese, diabetic patients,” Means said. “We find this very exciting and are trying to understand the mechanism responsible for this protective effect, as well as to identify more potent drugs to inhibit CaMKK2.”

"One of the key strengths of the Company's business platform is our ability to move drug candidates into clinical trials more quickly than traditional drug development", stated Mr. Pauls. "This is because we are using compounds that have already been approved for use in humans. The fact that DM-83 is a combination of two such compounds has allowed us to move it into a phase II trial in an expedient manner".

The inability to use insulin produced by the pancreas is a significant problem for people who suffer from Type 2 diabetes. This is demonstrated by the fact that many Type 2 diabetics have high levels of both glucose and insulin circulating in their bloodstream. DiaMedica believes that restoring insulin sensitivity and allowing the body to use its own naturally produced insulin is the key to combating this illness. Preclinical animal studies have demonstrated that DM-83 is able to restore insulin sensitivity to near pre-diabetic levels and has been shown to be safe.

Diabetes is a widespread and rapidly growing disease, affecting over 180 million people world wide with over 90% of diabetics being diagnosed with the Type 2 form of the disease. According to the World Health Organization this number is expected to double during the next 15 years while the American Diabetes Association has estimated the annual economic cost in 2007 to the United States to be $174 billion. Global sales of oral diabetes drugs total $6 billion today and are expected to climb to $11 billion by 2011.

About DM-83

DM-83 has demonstrated the ability to restore insulin sensitivity in an animal model of diabetes. The product is a novel combination of two known compounds with well established safety profiles that are used to treat other unrelated human conditions, one of which is used to improve cardiovascular conditions. Studies have shown that neither compound is able to restore insulin sensitivity on its own, while combining the two results in a synergistic effect that restores insulin sensitivity to pre-diabetic levels.

About DiaMedica

DiaMedica is developing novel treatments for various stages of type 2 diabetes. The Company recently completed a phase II clinical trial with its lead product DM-71 which demonstrated the ability to reduce HbA1c levels in man. The Company has two other drugs in its clinical pipeline, DM-83 and DM-99, which are moving through phase II proof of concept clinical studies.

Caution Regarding Forward-Looking Information

Certain statements contained in this press release constitute forward-looking information within the meaning of applicable Canadian provincial securities legislation (collectively, "forward-looking statements"). These forward-looking statements relate to, among other things, our objectives, goals, targets, strategies, intentions, plans, beliefs, estimates and outlook, including, without limitation, our anticipated future operating results, and can, in some cases, be identified by the use of words such as "believe," "anticipate," "expect," "intend," "plan," "will," "may" and other similar expressions. In addition, any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements.

These statements reflect management's current beliefs and are based on information currently available to management. Certain material factors or assumptions are applied in making forward-looking statements, and actual results may differ materially from those expressed or implied in such statements. Important factors that could cause actual results to differ materially from these expectations include, among other things: DiaMedica's early stage of development, lack of product revenues and history of operating losses, uncertainties related to clinical trials and product development, rapid technological change, uncertainties related to forecasts, competition, potential product liability, additional financing requirements and access to capital, unproven markets, supply of raw materials, income tax matters, management of growth, partnerships for development and commercialization of technology, effects of insurers' willingness to pay for products, system failures, dependence on key personnel, foreign currency risk, risks related to regulatory matters and risks related to intellectual property and other risks detailed from time to time in DiaMedica's filings with Canadian securities regulatory authorities, as well as DiaMedica's ability to anticipate and manage the risks associated with the foregoing. Additional information about these factors and about the material factors or assumptions underlying such forward-looking statements may be found in the body of this news release, as well as under the heading "Risk Factors" contained in DiaMedica's final long-form prospectus dated March 12, 2007. DiaMedica cautions that the foregoing list of important factors that may affect future results is not exhaustive. When relying on DiaMedica's forward-looking statements to make decisions with respect to DiaMedica, investors and others should carefully consider the foregoing factors and other uncertainties and potential events.

These risks and uncertainties should be considered carefully and prospective investors should not place undue reliance on the forward-looking statements. Although the forward-looking statements contained in this press release are based upon what management believes to be reasonable assumptions, DiaMedica cannot provide assurance that actual results will be consistent with these forward-looking statements. DiaMedica undertakes no obligation to update or revise any forward-looking statement.

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In this study, researchers looked at the genetic code of healthy, non-diabetic individuals whose blood glucose levels were in the normal range. They discovered that a single DNA mutation within three different genes explained, in part, why some individuals have high or low blood glucose levels. The researchers believe that these genes actually affect the threshold level of glucose in the bloodstream, which triggers the secretion of insulin. The higher the threshold, the higher the blood glucose level will rise before insulin starts to regulate it.

“These sequences explain about 5 per cent of the normal variation in blood glucose levels between otherwise healthy people,” explained Dr. Sladek, of McGill’s Faculty of Medicine, the Department of Human Genetics, the MUHC Research Institute and the McGill University and Génome Québec Innovation Centre. “Five per cent may not sound huge, but for complex traits, that’s rather a lot. By contrast, hundreds of different genes influence height.”

These findings provide important insights into the genetic mechanisms behind glucose metabolism, say the researchers, which they predict will lead to greater understanding of the genetic roots of metabolic disorders in general. “In theory, any medical test which has a genetic component can use this approach,” Sladek explained. “That brings us to the idea of ‘personalized medicine.’ Eventually, we might be able to customize treatment to an individual’s unique genetic structure.”

High blood glucose levels are also closely linked with increased risk for cardiovascular disease, and these findings hold out of the hope of discovering new management techniques and treatments. “It’s important to know that a high blood glucose level, even within the normal and non-diabetic range, is a risk factor for early mortality,” explains Dr. Philippe Froguel of Imperial College and CNRS. “Epidemiological studies have shown that 80 per cent of the risk of cardiovascular disease is related to a blood glucose level just above the average.”

“Obviously, the next step would be to get some collaborators on the heart disease side, and see whether some of these other genes might also play a role,” added Dr. Sladek.

“We are proud of this announcement, which once again confirms the scientific excellence and talent of Québec’s scientists,” said Paul L’Archevêque, President and CEO of Génome Québec. “These findings, which are the direct result of studies co-financed by Génome Québec, clearly show the strategic role of genomics in the search for solutions to improve human health. We would also like to underline the cooperation among the institutes, an initiative that made this major advance possible. Congratulations to Dr. Sladek and his team!”

"A major goal of the NIH research program in type 1 diabetes is to develop therapies that replace the insulin-producing cells destroyed by the autoimmune process," said NIH Director Elias A. Zerhouni, M.D. "These studies, which build on advances in immunology and transplantation research, may open the door to more widespread use of islet transplantation for patients with severe type 1 diabetes."

About 5 percent to 10 percent of the nearly 21 million people with diabetes have type 1, formerly known as juvenile onset diabetes or insulin-dependent diabetes. In type 1 diabetes, a person's own immune cells attack and destroy pancreatic beta cells, which produce the hormone insulin needed for survival. Beta cells, along with several other types of cells that work together to balance blood glucose, reside in islets, also known as islets of Langerhans, in the pancreas. Three or more insulin injections a day or treatment with an insulin pump are often needed to maintain blood glucose control, but most people with type 1 diabetes still develop complications, including damage to the heart and blood vessels, eyes, nerves, and kidneys. Despite steady improvements in managing the disease, type 1 diabetes cuts lives short by about 15 years, with early deaths due mainly to heart attacks and strokes.

In 2000, a research team led by Dr. James Shapiro at the University of Alberta in Edmonton, Canada, reported sustained insulin independence in seven patients transplanted with islets from two to four donor pancreases and treated with an immunosuppressive regimen that omitted glucocorticoids, thought to be toxic to islets. In the next few years, other researchers replicated the "Edmonton protocol," and most centers adopted this approach to islet transplantation.

The protocol greatly benefits some patients with severe type 1 diabetes, but two or more infusions of islets are usually needed, and the islets tend to lose their insulin-producing function over time. Participating in an islet transplant study is appropriate for people with severe hypoglycemia (dangerously low levels of blood sugar) and for those with type 1 diabetes who have had a kidney transplant to treat kidney failure, a complication of diabetes.

Since the Edmonton advance, scientists have been working to lengthen the survival of donor islets and reduce the side effects — such as anemia, nerve and kidney damage, and vulnerability to infection — of drugs that prevent the body's destruction of donor islets. In the new studies, the researchers will culture islets before transplantation to enhance their viability. They will also compare specific anti-rejection drugs for the ability to maximize islet survival while reducing toxicity. As the procedure becomes safer and new sources of beta cells become available, more people are likely to benefit.

The researchers are conducting pilot, or phase 1/2, studies of experimental agents as well as phase 3 studies that modify the Edmonton protocol. If the phase 3 studies succeed in safely controlling blood glucose levels, the investigators may ask the Food and Drug Administration to approve the procedure for people with poorly controlled type 1 diabetes. (For information about the phases of clinical trials, see http://www.fda.gov/fdac/features/2003/503_trial.html.)

"If these approaches are successful in prolonging islet function with less drug toxicity, type 1 diabetes patients with severe problems controlling their blood glucose may have another treatment option for controlling their diabetes," said study chair Dr. Camillo Ricordi of the University of Miami.

The studies are enrolling individuals with type 1 diabetes who have serious difficulty controlling their blood glucose despite intensive medical therapy and who suffer from episodes of severe hypoglycemia (dangerously low levels of blood glucose). Also eligible are patients with severe hypoglycemia and hypoglycemia unawareness, who cannot sense a drop in blood glucose and may lose consciousness without warning. In addition, researchers are accepting type 1 diabetes patients who have had a kidney transplant and are already taking immunosuppressive drugs. For more information about the studies, call 1-877-IsletStudy (1-877-475-387-8839) or see http://www.citisletstudy.org/index.html.

The following researchers are conducting the studies:

* Dr. Camillo Ricordi, study chair
University of Miami
* Dr. Christian Larsen
Emory University, Atlanta
* Dr. Dixon Kaufman
Northwestern University, Chicago
* Dr. Bernhard Hering
University of Minnesota, Minneapolis
* Dr. Ali Naji
University of Pennsylvania, Philadelphia
* Dr. Peter Stock
University of California, San Francisco
* Dr. James Shapiro
University of Alberta, Edmonton, Canada
* Dr. Jose Oberholzer
University of Illinois at Chicago
* Dr. Aksel Foss
University Hospital Rikshospitalet, Oslo, Norway
* Dr. Olle Korsgren
Uppsala University Hospital, Uppsala, Sweden
* Dr. Annika Tibell
Karolinska University Hospital, Stockholm, Sweden

Dr. William Clarke oversees the Consortium's Data Coordinating Center at the University of Iowa.

Their results have shown that resveratrol improves glycemia by stimulating glucose transport in certain tissues including the skeletal muscle that expresses the insulin-sensitive Glut4 isoform of glucose transporters. However, the research by Drs. Martin and Ismail-Beigi shows that in cells expressing the Glut1 isoform, resveratrol blocks glucose transport by binding and inhibiting the Glut1 transporter. This may be of importance because certain cells and tissues, including brain, retina, placenta, and red blood cells express large amounts of this transporter. Hence, the presumed inhibition of the Glut1 transporter in these tissues in-vivo may have undesired and negative effects on their normal function.

“It’s exciting to see resveratrol’s glucose-lowering effect in diabetic experimental animals,” Dr. Martin said. “However, studies are currently underway in our laboratory to determine whether the agent inhibits glucose transport in the brain of normal and diabetic animals.”

At the 2008 AACE Annual Meeting, diabetes will be taking center stage. A special symposium titled “Clinical Trials Targeting Glycemia: What Do We Expect to Learn?” will consider the impact of glucose control through studies including ACCORD, ADVANCE, VADT, and others. Other sessions of interest include “Insulin Resistance and Atherosclerosis: The Missing Link,” “Diabetes: A Cardiac Condition,” and “Hypoglycemia: The Limiting Factor in the Glycemic Management of Diabetes.”

“The main implications of our research are suggestions for more high quality, long-term trials in healthy pregnant women, with larger sample sizes and reporting all clinically relevant outcomes, to address dietary issues more thoroughly and provide more conclusive results,” said lead review author Joanna Tieu.

“Our results suggest that a low glycemic index diet may be a benefit to mother and child, however,” said Tieu, at the Women and Children’s Hospital at the University of Adelaide in Australia.

“This is because low glycemic index diets — such as fresh fruits and vegetables and unprocessed whole-grain foods — tend to slow down the digestion of food. Slow digestion allows the body to better adjust to the load of sugar coming in after a meal,” she said.

“While our results were promising, the evidence is not sufficient to recommend changes in clinical practices, because of the limited number of trials,” Tieu said.

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

The review authors found few clinical trials to include in their review. The three eligible studies included only 107 women living in the United States, Australia and the United Kingdom.

Doctors do not understand exactly what causes gestational diabetes, but they suspect that hormones from the placenta block the action of the mother’s insulin. Without enough insulin, sugar (glucose) cannot enter cells, where it is needed to fuel cell activity. Instead, sugars build up in the bloodstream, causing hyperglycemia.

These excess sugars and other nutrients flow through the placenta and into the baby’s cells, giving the baby more energy than it needs to develop. Stored as fat, these excess sugars may cause the baby to grow quite large — more than 8.8 pounds — or greater than the 90th percentile, compared to other babies.

A large baby may get wedged on the mother’s pubic bone during delivery, for example, putting the baby at risk for a number of health problems, including fractures or brachial plexus injuries, which can damage the network of nerves connecting the spine with the shoulder, arm and hand.

“Gestational diabetes also has been associated with spontaneous labor and premature birth,” Tieu said. “And children of women with gestational diabetes are at increased risk of obesity, glucose intolerance and diabetes in late adolescence and young adulthood.”

Mothers with gestational diabetes are at increased risk for preeclampsia (hypertension) or placental abruption during pregnancy. Induced births or Caesarean sections are more common, adding even more health risks. These women also have an increased risk of developing diabetes in the future.

Obstetrician Seth Brody, with Wake Medical Center in Raleigh, N.C., said that very large studies with longer follow-up are necessary to determine whether dietary changes can alter significant health outcomes. He suggests that in the future studies, researchers should go beyond simply knowing the difference in babies’ weights and serum glucose levels because these are not health outcomes of clinical significance.

“If the difference in birth weight were significant enough to be reflected as a difference in birth injury rates, Caesarean delivery rates and the need for operative deliveries, then that difference is of clinical importance, as is studying rates of brachia plexus injuries, fractures or neonatal mortality.” he said. “If a low glycemic diet altered the incidence of treatment for short- or long-term metabolic issues for either mom or baby, then those would be very important health outcome differences to determine, as well.

“At this point, it is most reasonable to continue to recommend the appropriate diet, weight gain, and exercise guidelines to all pregnant women, as outlined by the American College of Obstetrics and Gynecology,” Brody said.

The Cochrane Collaboration is an international non-profit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.

American College of Obstetrics and Gynecology guidelines for pregnant women are available at http://www.acog.org

Tieu J, Crowther CA, Middleton P. Dietary advice in pregnancy for preventing gestational diabetes mellitus (Review). Cochrane Database of Systematic Reviews 2008, Issue 2.

They found high levels of E-selectin and white blood cell count with low levels of serum albumin were clear predictors of high risk for type 2 diabetes. The researchers found that traditional risk factors such as obesity or family history helped identify 65% of all patients who were at high risk of developing type 2diabetes. But when the information from these three markers was added this increased from 65% to 73% which means doctors could be able to spot a greater number of people at risk of type 2 diabetes at an early stage.

The research used data taken from the Western New York Health Study. This was a six-year longitudinal study of diabetes and cardiovascular risk factors among residents of Erie and Niagara Counties, New York.

Dr Stranges said: "High levels of E-selectin and white blood cells with low levels of serum albumin can indicate endothelial dysfunction and sub-clinical systemic inflammation. These findings corroborate the notion that both these conditions play an important role in the development of the disease. Endothelial dysfunction is also regarded as a key event in the development and progression of atherosclerosis. Finding new markers for type 2 diabetes will help us gain a greater understanding of the condition and possibly open up new possibilities for the way we prevent and treat it."