Research News

[belyro]

This was in a copy of a local diabetes newsletter. It might not be "news" to everyone here, but I thought some of you might find it interesting to read.

Research News

September 2006: JDRF funded researchers at The University of Western Ontario and at the Medical College of Georgia have made important progress with clarifying the role of a gene that impacts autoimmunity in diseases like type 1 diabetes. This research shows that a gene called Aire controls the development and maturation of certain immune cells that protect against autoimmune attack. When Aire does not function properly, protective immune cells called invariant natural killer T cells (iNKT) cannot develop properly to perform their defensive role. Without iNKT cells preventing autoimmune attack, pancreatic beta cells can be targeted by the immune system (leading to type 1 diabetes). This work helps shed light on the cause of autoimmune diseases such as type 1 diabetes and may lead to strategies that could block them. The most recent publication by this team can be found in the journal Nature Medicine (Vol.12, No.6, p.624, 2006).

Autumn 2006: A new study from France provides more evidence that wide swings in blood sugar levels may actually damage the body as much as prolonged periods of high blood sugars. This study provides evidence that blood sugar fluctuations trigger oxidative stress and changes cellular metabolism that leads to cell damage and cell death and contributes to complications. It is well known that prolonged high blood sugars had this effect, but this study also shows that repeated swings of very high and very low blood sugars can be equally damaging.

This is also one of the main reasons your health care professionals are always so interested in you keeping and reviewing your blood sugar records IN ADDITION to having your current HbA1c result. HbA1c results can be misleading. Two people with the same HbA1C may have dramatic differences in the number of glucose excursions – when blood glucose levels departed from the normal range and either go too high or too low. This research showed two main things: 1) patients with more blood glucose fluctuations had higher levels of biochemical markers for oxidative stress and 2) the correlation between blood glucose fluctuations and oxidative stress was more direct than the relationship between sustained hyperglycemia and oxidative stress. This research comes with a helpful warning to all people with type 1 diabetes of the value and importance of continuing to work at curbing such fluctuations to reduce the risk of complications. You can read more about this study in the Journal of the American Medical Association (Vol. 295, No. 14, p. 1681, 2006).

September 2006: Dr. Shapiro and a team of leading scientists have just published the results of their recent international trial of the Edmonton protocol for islet transplantation. While islet cell transplantation has not produced the long-term results initially hoped for that would make it therapeutically accessible to the diabetes population at large, the dramatic discoveries are encouraging and many advances and breakthroughs will certainly continue. It is important to realize how far this field has come in a relatively short time. Prior to the Edmonton protocol in 2000, islet cell transplants had a 1-year graft survival of less than 2%. After the Edmonton protocol, Dr. Shapiro’s team saw 1-year graft survival rates of more than 80%. The challenges of islet transplantation have been and still remain: 1) difficulty accessing donor islets, 2) difficulties in extracting and purifying islets, 3) our limited understanding of how immunology works, and 4) the use of immunosuppressive drugs for recipients. These challenges have opened many doors for increased learning, understanding and potential breakthroughs via stem cell research, xenotransplantation and islet encasement, and immune tolerance research.
The international trial took place in major centers world-wide, in Edmonton, the US and Europe to see if the complicated knowledge and techniques used to prepare and transplant human islets could be reproduced with good result in other centers. Researchers screened more than 2000 subjects for eligibility. 36 patients met strict study criteria (4 patients at each center). 58% of the 36 patients reached insulin independence at some point during the trial, but 76% had become insulin dependent again by 2 years after transplantation.

A Short List of Diabetes Firsts From The Discovery of Insulin to Present Day!

1921 – Insulin discovered
1922 – Regular insulin first used
1946 – NPH insulin developed
1978 – First insulin infusion pump developed
1983 – First implantable pump; recombinant human insulin developed (humalin)
1980’s – Growth in organ transplantation, use of cyclosporine, muromonab-CD3, preservative solutions
1990’s – Large growth in pancreas transplantation and development of immune suppressive drugs
1999 – Insulin analogues developed (aspart, glargine)
2000-2006 – Development of Edmonton protocol, ground breaking work in stem cell research, immune tolerance and xenotransplantation

[BriOnH]

I believe xenotransplantation will be the next best therapy. Welcome to MicroIslet Inc. (http://www.Microislet.com) . If they would just stick to their schedules better! They need better project managment. Big time. I just recently cashed out my stocks there. Feel bad about it, but they are sucking.

[belyro]

Just thought I'd pass on the latest "news" from the local diabetes newsletter I get.

Research News

December 2006: Researchers at Toronto’s Hospital for Sick Children, the University of Calgary and the Jackson Laboratory in Maine published findings of a study done in mice in the Dec 15, 2006 issue of Cell that suggest type 1 diabetes could potentially be treated or prevented with drugs that work on the nervous system. The group discovered that 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. When researchers removed the sensory neurons, it prevented inflammation of the cells and the mice did not develop diabetes. An injection of substance P into the pancreas also cleared islet cell inflammation in the mice and normalized the elevated insulin resistance associated with diabetes. This research suggests that defective sensory nerves help start, and maintain, diabetes in diabetes-prone individuals. TRPV1 defects may also play a role in other autoimmune diseases such as Lupus and rheumatoid arthritis. More research is now needed to show if this will prove the same in humans as it does in mice and whether these abnormalities start early in life and if they contribute to disease development. There will be much excitement if these studies are indeed confirmed in humans.

December 2006: A research team at the Wake Forest University Baptist Medical Center and at the University of Heidelberg has proven that a specific gene called the carnosinase 1 gene, located on human chromosome 18 protects some people with diabetes from developing severe kidney disease. This team evaluated 858 individuals including people with diabetes and end-stage kidney disease on dialysis, people with diabetes with normal kidney function and healthy non-diabetic individuals. They confirmed the protective form of the carnosinase 1 gene was present in greater frequency among both healthy individuals and diabetic subjects without kidney disease, compared to the patients on dialysis who more commonly had forms of the gene that were not protective. This gene produces an enzyme called carnosinase which inactivates the protective substance called carnosine. Carnosine appears to prevent scarring from developing in the kidney tissue and serves as a scavenger of damaging oxygen-free radicals. This discovery holds promise as a marker to help identify those at increased risk and for novel new treatment strategies in susceptible people with diabetes to protect them from kidney failure.

January 2007: You have heard of inhaled insulin and you may have heard of new techniques testing encapsulated insulin, but have you heard of insulin synthesized from plants? The Canadian firm SemBioSys Genetics announced that its proprietary plant-produced insulin made from the safflower plant has been shown to be indistinguishable from human insulin, namely Eli Lilly’s Humalin and U-S-P insulin, opening up a whole new potential source of insulin and reducing product costs by up to 40% or more. The company has been able to achieve a 1.2% accumulation of insulin in the seed protein of the plant, exceeding its commercial target. At this level of production, one acre of safflower would be enough to supply 2,500 patients with a year’s supply of insulin. The Canadian firm Cangene has been chosen to handle processing and purification of this new insulin which is targeted to hit market by 2010. You can read more about this new insulin on the news section of Pharmaceutical industry and manufacturer - Pharmaceutical news, packaging and technology (http://www.in-pharmatechnologist.com) . Thanks to Angela G, Maestro Participant, for bringing this to our attention! [I think this is DF's very own Ang from Winnipeg!]

January 2007: Novo Nordisk announced January 31st that the United States Food and Drug Administration (FDA) has approved NovoLog(R) (insulin aspart, Lantus) as a safe and effective treatment for pregnant women with type 1 diabetes and their unborn children. Lantus is still NOT approved for use in pregnancy in Canada, but with this announcement and new evidence, it shouldn’t be too long before it is. The FDA category change was based on research done in 63 sites in 18 countries comparing the safety and efficacy of insulin aspart versus human regular insulin in the treatment of 322 pregnant women with type 1 diabetes. Results showed that changes in A1C and rates of maternal hypoglycemia were comparable with the two insulins. The trial with insulin aspart showed improved outcomes for both mother and child in terms of fewer preterm deliveries, reduced risk of neonatal hypoglycemia, consistent low rates of major hypoglycemia and reduced risks to the fetus with pregnancy outcomes comparable to those in the human regular insulin arm of the trial.

[belyro]

Just received this correction:


Under the January 2007 news about Novolog, it should be noted that Novolog is Insulin Aspart as indicated BUT NOT LANTUS, rather it is Novorapid here in Canada. The following statement that is made regarding Lantus not being approved for pregnancy in Canada is true, and this also holds true for Detemir (Levemir). The approval of Novorapid in pregnancy should not be linked to the hope that soon Lantus or Detemir will be approved as the rapid analogs are vastly different from the long acting analogs.

[belyro]

Here's the latest from my local newsletter:

Research News

February 2007: Day in and day out, taking care of your diabetes is hard work, but the good news is, it’s worth it!! According to a recent report released from the Canadian Institute for Health Information, the number of people newly diagnosed with kidney failure with type 1 diabetes has decreased 42% in the last 10 years. Researchers attribute this very significant decrease to new advances and improvements in treatment and interventions that have helped improve self management for people with type 1.

January 2007: Exciting things happening in the area of treatment and prevention of retinopathy!

1) JDRF funded researchers at the Joslin Diabetes Center in Boston have identified a group of proteins that may play a critical role in causing blood vessel leakage in people with two forms of diabetic retinopathy, macular edema and proliferative diabetic retinopathy. These proteins are found in the human vitreous, the gel that fills the cavity between the lens and the retina of the eye. Researchers analyzed these proteins in people with and without diabetes and with diabetes and with and without retinopathy, and detected 117 proteins, 31 that were just present in the vitreous of the patients with diabetes. By further analyzing those 31 proteins, they discovered that high levels of carbonic anhydraise 1 (CA-1), an enzyme that is normally found in red blood cells, causes leakage of retinal blood vessels, which contributes to the retinal swelling often associate with advanced diabetic retinopathy. These findings suggest potential new therapeutic targets for the treatment of proliferative diabetic retinopathy and macular edema and could provide new opportunities for treating cerebral swelling caused by head injury, stroke and other conditions involving neurovascular tissues.

2) Recent results of a phase III clinical trial funded by Eli Lilly conducted at 70 sites across the US showed that a new drug, ruboxistaurin was effective in slowing the progression of retinopathy. Ruboxistaurin works by inhibiting an enzyme in the body called protein kinase C beta (PKC beta), believed to contribute to the blood vessel damage that can lead to diabetic retinopathy. Patients in the study who were treated with the new drug did significantly better than those in the placebo group, suffering sustained visual loss at about half the rate of the placebo group. More testing is needed to determine safety and efficacy before the FDA will approve it for use, but to date, this is the first oral drug that has been shown to protect against the progression of diabetic retinopathy in human studies. You can bet we’ll be keeping an eye on this (No pun intended)!!

[Injecto]

Wow, the surprising thing I've learned from the article, relating to kidney failure (Number of new diabetes-related kidney failure patients more than doubles in 10 years (http://secure.cihi.ca/cihiweb/dispPage.jsp?cw_page=media_07feb2007_e)) is the number of patients. In 2004 there were only 303 Type 1 newly diagnosed? That number just seems so small....it almost makes me worry a lot less.

[belyro]

Not sure if anyone's reading these, but I'll keep posting them when I get them, just in case.

Research News

August 2007: Islet cell transplants, accompanied by the necessary nasty immune-suppressing drugs, has had highly variable results, from well to poorly tolerated for individuals undergoing this form of therapy. Part of the problem is an inability to track the transplanted beta cells once they are inside the body. Researchers at Johns Hopkins have found a new way to overcome this obstacle. Their new technique encapsulates the new insulin-producing cells in tiny porous capsules made from a mixture of alginate (made from seaweed) and Feridex, a magnetic iron containing material visible under MRI (magnetic resonance imaging). This new technique has been tried and tested in pigs and mice with very good result in blood sugar normalization and avoided rejection by the immune system. Researchers are hopeful that this new technique will also be successful with humans and could be used to make tissue-type matching and immunosuppressive drugs problems of the past. This work is published in the current issue of Nature Medicine.

July 2007: A team of scientists in Canada and the US have uncovered a gene variant that is thought to increase risk for type 1 diabetes. This new gene is called KIAA0350 and sits on chromosome 16. It appears to play an important role in the development and maintenance of type 1 diabetes. It is thought that this gene may be one of approximately 15 or more that work together to wipe out insulin producing cells. This is an exciting breakthrough because it means scientists are slowly beginning to get a picture of what the genetic predisposition for type 1 may look like. This group of scientists had access to DNA samples of patients and their families attending pediatric diabetes clinics in Philadelphia and four cities in Canada. They scanned the genomes of 1,046 children with type 1 diabetes and searched over 500,000 genes in each individual for markers for type 1. KIAA0350 needs to be investigated further for the researchers to find out exactly what it does, however, they hypothesize that a special mutation in this gene may influence the sugar binding of a certain protein (possibly C-type lectin) and trigger an autoimmune response that activates natural killer cells in such a way that they attack and destroy the islet cells in the pancreas. You can read more about this research in the journal Nature published online July 15, 2007. (Some of you may even recognize some of the author names as this work has a definite familiar feel: Dr. Shayne Taback - Pediatric Endocrinologist here in Winnipeg with the Pediatric Endocrinology Research Group, Dr. Margaret Lawson, Pediatric Endocrinologist from Ontario, and Dr. Constantin Polychronakos from Montreal - the “GGG” - Great Greek Geneticist, head of the Triple G Study!)

[Injecto]

Not sure if anyone's reading these, but I'll keep posting them when I get them, just in case.


Yeah, some of us are reading them. Keep em up.

I really feel that the whole islet cell thing is a great idea in theory that will just never pan out. When I was dxd, the first thing my GP said was how much advancement has happened in the Islet cell research and I was like, WTF is on Island Cell etc....LOL.

I still love that "insulin that is encapsulated by a protein that disintegrates when sugars rise". The thought of injecting once a day and forgetting about everything else seems like THE best treatment ever.

[belyro]

Research News

September 2007: A 10-second full–out sprint performed just before engaging in moderate-intensity exercise may help prevent early falls in after-exercise blood sugars according to research done in Perth, Australia. Investigators tested 7 complication-free males 21.6 years of age (±3.6 yrs) with type 1 diabetes and A1C’s in the 7.3% to 7.5% range.

Subjects were randomized into either a test or control group. All participants injected their usual morning insulin dose and ate their normal breakfast. When post-meal blood sugars fell to ~11mmol/L, participants in the test group were asked to perform a 10-second all-out sprint immediately before cycling at a moderate-intensity pace for 20 minutes. The control group was asked to just rest immediately before cycling.
Results showed that sprinting did not affect the rapid fall in blood sugars during the moderate-intensity exercise session. During the 45 minute period of recovery after exercising, blood sugars in the control trial fell by ~1.23 mmol/L while the blood sugars of the participants in the sprint trial remained stable, only later decreasing at a similar rate to those in the control trial. Meaning, the 10-second sprint helped to prevent immediate after-exercise lows, but not delayed after exercise lows. This is due to a significant increase in noradrenaline and lactate levels during the sprint. Authors did caution that this research was done in a controlled laboratory setting and that before trying this at home, you know how your body reacts to intensive and moderate periods of exercise. More information about this research can be found in the September 2007 issue of the journal Diabetologia.

Summer 2007: Researchers in 14 centers in the US and 3 confirmed sites in Canada (Toronto, Montreal and Winnipeg) are working with affiliate sites and participating physicians in Type 1 Diabetes TRIALNET, to begin clinical studies using oral insulin to prevent or delay type 1 diabetes in people not yet diagnosed, but who are at risk for type 1 diabetes. Research has shown that the pancreas is resilient and more than half its insulin-producing beta cells must be irreversibly destroyed before an individual develops symptoms of diabetes. Researchers are studying whether an insulin capsule taken by mouth once a day can prevent or delay onset of type 1 diabetes.

An earlier trial suggested that oral insulin might delay type 1 diabetes for about 4 years in some people with islet cell autoantibodies in their blood. The presence of these autoantibodies alerts physicians to the destruction of insulin-producing cells up to 10 years before symptoms set in and indicates an individual is at greater risk. For a person with high-risk genes (relatives with type 1 diabetes) and all three autoantibodies, the risk of developing diabetes in the next 5 years is greater than 50%. Animal studies have also suggested that insulin taken orally might even prevent type 1 diabetes.

[belyro]

Research News

October 2007: Researchers in Japan and the US have described a process of differentiating rat pancreatic ductal epithelial cells into insulin producing cells – a major breakthrough in stem cell research. Over recent years, great efforts have been made to differentiate embryonic stem cells, pancreatic ductal epithelial multipotent progenitor cells and bone marrow stem cells into islet cells. Those of you who were at the last Maestro evening dinner event heard Josh Manusow talk about his summer work researching progenitor cells and the need to find a large, readily available source of non-rejectable islets for transplantation. The results of this study suggest a promising future. You can read more about this breakthrough research in: World Journal of Gastroenterology 2007; 13(39):5232-5237or in the recent issues of the journals Cell by scientists at Kyoto University and Science by researchers at the University of Wisconsin.

November 2007: Scientists at the University of Virginia Health System are beginning to understand what unleashes the immune attack on pancreatic beta cells and have identified an enzyme thought to be an important instigator of the inner-body conflict that causes type 1 diabetes. The researchers focused on a single gene, 12/15 lipoxygenase (12/15-LO). This gene leads to the production of the enzyme, which appears to have an important role in the activation of white blood cells in the pancreas. They developed a non-obese diabetic female mouse model to test turning off the 12/15 OL gene to study its effect. They discovered that these mice without the enzyme were 97% less likely to develop diabetes than mice that had normal levels of the enzyme. They also discovered that the study mice that did not have the 12/15 LO gene and remained non-diabetic demonstrated better glucose tolerance than non-diabetic NOD mice that were matched for age. (Worse glucose tolerance is an indication of having pre-diabetes). The same group of study mice also had improved beta cell mass and less severe insulitis than the non-diabetic NOD mice. (Insulitis is a change in the islet cells that includes a high-fluid volume and too many white blood cells. White blood cells normally help to fight off infections, but they can cause damage over time when they infiltrate the islet cells of the pancreas). This research is exciting because it has two practical applications. First, it helps in the understanding of the process that produces self-destructive white blood cells, which can be useful in predicting who may be at risk for developing type 1 BEFORE significant damage has occurred in the islets. Second, researchers may be able to design drugs to target this specific enzyme that may help prevent type 1 in people at risk and to prevent recurrence of type 1 in transplanted islets. This was a breaking news report and more information about this research will be published in the upcoming February 2008 issue of the journal Diabetes.

[belyro]

Research News

February 2008: Researchers at the Joslin Diabetes Center have reported that women with type 1 diabetes who skip their prescribed insulin dose have a three-fold increased risk of diabetes related complications and early death than those who do not skip their insulin. This study, reported in the March issue of Diabetes Care highlights the extreme dangers of insulin omission and insulin restriction. This evidence was from an 11-year follow-up study of 234 women and showed an increased risk of mortality as well as higher rates of kidney and foot problem in those who restricted their insulin. The authors highlighted the important link between diabetes and eating disorders that puts individuals at especially high risk for insulin omission. Whether you are male or female, if you struggle with missing your insulin – you need help. Please talk to a member of your healthcare team about this.

March 2008: Researchers in gastrointestinal genetics at Barts and The London School of Medicine have discovered an additional seven gene regions implicated in the immune responses causing celiac disease. Of the nine now known celiac gene regions, four of these are also predisposing factors for type 1 diabetes. This research sheds light not only on the nature of celiac disease, but on the common origins of both diseases. Celiac disease is prevalent in about 1% of the population in the Western World. It is an immune-mediated disease triggered by intolerance to gluten (a protein found in wheat, barley and rye containing foods). Celiac disease prevents normal digestion and absorption of nutrients and if undetected it can lead to problems like poor bone health, anemia and unhealthy weight loss. Currently, only adherence to a gluten-free diet can diminish symptoms.

March 2008: Scientists at Massachusetts General Hospital have initiated a phase 1 clinical trial to explore whether the promising results from the lab of Dr. Denise Faustman can be applied in human diabetes. Dr. Faustman’s previous studies have shown that a commonly used vaccine that provides protection from tuberculosis, called Bacillus Calmette-Guerin (BCG) can be used to deplete abnormal immune cells that attack and destroy insulin-producing cells in the pancreas, effectively curing type 1 diabetes in the study animals. The first step in this trial is to determine whether this same strategy using this BCG vaccine will work in humans. Check this for more information on this clinical trial: Determination of Dosing and Frequency of BCG Administration to Alter T-Lymphocyte Profiles in Type I Diabetics - Full Text View - ClinicalTrials.gov (http://www.clinicaltrial.gov/ct2/show/NCT00607230)