Researchers identify source that causes Type 1 diabetes

Doctors at Eastern Virginia Medical School's Strelitz Diabetes Center have been stalking the culprit responsible for Type 1 diabetes. Now, they are one step closer.

Members of a research team at the center, led by Jerry Nadler, MD, professor and chair of internal medicine and director of the center, have been studying the role of the enzyme 12-Lipoxygenase (12-LO) in the development of Type 1 diabetes. They hope that targeting this enzyme will hold the key to a cure.

Dr. Nadler and several research colleagues in the EVMS Department of Internal Medicine, including Kaiwen Ma, PhD, research instructor; Swarup K. Chakrabarti, PhD, research assistant professor; and David A. Taylor-Fishwick, PhD, associate professor, recently published their findings in the February issue of The Journal of Clinical Endocrinology and Metabolism.

Type 1 diabetes is a chronic condition that develops when the pancreas stops generating enough insulin to maintain normal levels of glucose (sugar) in the blood. Insulin moves sugar from the bloodstream to cells so that it can be used to generate energy. In Type 1 diabetes, a person's immune system attacks the insulin-producing beta cells, found only in the pancreas. When the beta cells die, the body no longer can produce enough insulin to regulate blood-glucose levels, and this can lead to serious health complications, even death, without treatment.

It is generally understood that inflammation plays a vital role in beta-cell destruction. But the precise factors are not well known. A protein-based enzyme found in beta cells, 12-LO produces specific lipids that cause inflammation and can lead to the death of beta cells in laboratory models. In fact, EVMS researchers have demonstrated that deleting the gene that produces 12-LO prevents the development of Type 1 diabetes in mice.

The challenge has been to validate that 12-LO and its pro-inflammatory lipid products have a role in human diabetes. Gaining access to human beta cells can be difficult, but EVMS is among a limited number of research groups that can receive human islets - the region of the pancreas that contains beta cells - from individuals who have donated their bodies to science through the Juvenile Diabetes Research Foundation Islet Resource Center Consortium Dr. Nadler explains.

Thanks to that resource, the EVMS team has confirmed that 12-LO is indeed found in human islets, and in humans, like in mice, its pro-inflammatory lipid products can lead to lower insulin production and beta cell death.

Juvenile Diabetes Type 1

by Jason Matlock

Diabetes is quickly becoming commoner nowadays as the number of folk diagnosed every year increased by 48% between 1980 and 1994 and nearly all of the new cases are Type two Diabetes. This is not only a pandemic, but also one that must be found a cure.

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As you'll, or may not, already know, Type two Diabetes is the commonest type of Diabetes that can really be cured with a little bit of effort. It's also known as non-insulin dependent diabetes and it affects 90-95% of the entire twenty-one million person community who is unfortunate enough to have it.
They're also considered to have a variety of autoimmune disease because their body disables their own defenses of the cells that are wanted to produce said insulin.

Folk with Type 2 Diabetes produce insulin via their pancreas, which separates them from Type 1 ( folk who are resistant and can't produce it themselves ). the difference is that for folk with Type 2, the insulin is either not enough or the body simply ignores it and is not correctly used because they are resistant to it also.
Being diagnosed as having Type two Diabetes can be very frightful, but it's's not the end of the world as it can be cured naturally. It's critically crucial that you arm yourself with as much information as practical to not only cure diabetes, but also to stop it in the future and help out those around you who could be showing signs and symptoms.

When it all boils down to which sort of diabetes is worse, it would seem that Type one not only gets the nomination, but also wins the award as well! Most of the people with Diabetes think that they're stuck with the condition for life and that there isn't anything that they can do about it. The excellent news is that they are wrong! Diabetes can be cured thru diet and exercise and I have personally witnessed folks utterly go off their medication by making significant changes to their daily habits.
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Hypoglycemia Type 1

Insulin Pumps Might Have Slight Advantage In Type 1 Diabetes

A new evidence review suggests that using a pump to deliver insulin continuously - instead of taking three or more daily injections - might result in better control of blood sugar for people with type 1 diabetes.

"The findings of this review tell us that both continuous subcutaneous insulin infusion and multiple injections correct blood glucose levels. However, [continuous infusion] may be better for reducing harmful fluctuations in blood glucose," said lead author Marie Misso, Ph.D.

Type 1 diabetes - which used to be known as juvenile diabetes - results when the pancreas is not able to secrete enough insulin, causing the levels of glucose (or sugar) in the blood to rise.

Chronically high blood glucose can lead to heart attacks, circulation problems and blindness. Low levels can lead to unconsciousness and even death. Type 1 diabetes is one of the most common chronic diseases of childhood.

Most people with the condition control their glucose by injecting themselves with insulin three or more times per day. Others choose to use a pump, which gives continual, smaller doses of insulin without the discomfort of injections.

"There are numerous studies that evaluate these treatments, but most are of poor quality," said Misso, a research fellow at the Monash Institute of Health Services Research in Clayton, Australia. "So there has been uncertainty about which treatment is best for maintaining consistent levels of blood glucose and reducing harmful fluctuations."

In the new review, Misso and colleagues analyzed the results of 23 studies that assigned 976 adults and children to one of the two interventions randomly. Researchers looked at measures such as levels of hemoglobin A1c (or HbA1c), a widely used marker for assessing long-term glucose control. They also looked at the incidence of both high and low blood glucose.

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.

While participants using the insulin pump had significantly lower HbA1c levels than those using multiple daily injections, no differences existed between the two for non-severe low blood glucose levels. However, there appeared to be a reduction in severe incidents of low blood glucose among those using the pump.

"Good evidence is now available to support the use of continuous subcutaneous insulin infusion in the appropriate patient. It is essential to consider adverse events, late complications of diabetes, mortality and cost when deciding whether [a pump] is appropriate for the patient," Misso said.

For people who likely have to deal with their condition for the rest of their lives, convenience is another consideration that comes into play.

The advantages of using the insulin pump include being able to avoid possibly painful injections several times a day. In addition, pumps administer the medication without the user having to find a private place to give the injection.

The downside to pump use includes having to wear it like a pager or cell phone throughout the day, concerns about protecting the tubing that goes into the body - although wireless pumps have recently come on the market - and worries about breaking the pump during rough play or exposure to water.

Ramin Alemzadeh, M.D., director of the Diabetes Program at the Children's Hospital of Wisconsin in Milwaukee, cautioned that although the researchers reported pumps might improve glucose control overall, pediatric patients should not expect major changes in the longer-term control of blood glucose.

"In our experience, we don't see a significant overall blood glucose improvement beyond six months or one year of treatment in most children and adolescents. Initially, the patient's HbA1c levels improve, but after a while levels begin to rise and are not significantly different from where they started," Alemzadeh said. "A patient's diabetes management starts with them and their family. How well they do is independent of which method of insulin administration they use."

The review discloses that one of the co-authors has received compensation for lectures and advisory board participation from companies who make insulin or insulin pumps. His department has also received funding for research and educational activities from these companies

Type 1 diabetes youth have abnormal insulin resistance that may increase risk of cardiovascular disease

According to a new study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM), youth with type 1 diabetes have now been found to have abnormal insulin resistance. Having abnormal insulin resistance appears to negatively affect heart, blood vessel and exercise function in this population.

Type 1 diabetes often begins in childhood. Patients with type 2 diabetes have their insulin resistance measured routinely, but this is currently not common practice in treating patients with type 1 diabetes--especially those with normal weight. Because insulin resistance is known to contribute to cardiovascular disease in type 2 diabetes researchers in this study investigated whether insulin resistance has a similar effect on adolescents with type 1 diabetes.

In this study, researchers measured insulin sensitivity and heart, blood and exercise function in 12 adolescents with type 1 diabetes and compared these measurements with measurements from 12 control patients without diabetes, but similar in age, pubertal stage, activity level and body mass index. They found that insulin resistance may affect long-term cardiovascular outcomes in type 1 diabetes as is found in people with type 2 diabetes. Specifically, results indicate that insulin resistance is directly related to decreased heart and vessel function and appears to impair capacity to exercise.

"Cardiovascular disease is the major cause of death in adults with diabetes, but until now, little was known about the effects of type 1 diabetes on cardiovascular health in youth," said Kristen Nadeau, MD, of the University of Colorado Denver, and lead author of the study. "Our data suggests that while youth with type 1 diabetes may not present conditions typical of insulin resistance, such as obesity, insulin resistance is present and may affect long-term cardiovascular outcomes in this population."

"Our study is one of the first definitive studies showing the presence of insulin resistance in youth with type 1 diabetes and this may have significant implications for the cardiovascular health of these patients," said Nadeau. "Increasing our understanding of the mechanisms underlying insulin resistance in adolescents with type 1 diabetes will direct future research and therapeutic interventions. If insulin resistance is addressed early in the care of patients with type 1 diabetes, it may be possible to decrease cardiovascular morbidity and mortality in this population."

Complications Diabetes Type 1

by John Hash

Type 1 diabetes : Type 1 diabetes is affecting about five % of all people who have diabetes.It is often referred to as juvenile diabetes because there is a increased rate of diagnosis in kids between the ages of 10 and fourteen, but people of any age group can develop type 1 diabetes. It may also be called insulin-dependent diabetes, because diabetes pills are ineffective in treating the high blood glucose level ; these people require injections of insulin to manage their blood glucose.

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Typically, white blood cells are responsible for recognizing foreign objects in our blood and then attacking these foreign objects with antibodies. In type 1 diabetes, the white cells think the beta cells of the pancreas do not belong there. A swelling ensues and the white cells attack the beta cells. When enough beta cells are lost, insulin deficiency develops and blood glucose levels begin to rise.

Sometimes you can identify the viral infection that set off the attack, but generally no such sickness can be identified. This is particularly common in African and Chinese US citizens.

In type one diabetes, there is a chance of developing ketoacidosis due to the extraordinary shortage of insulin. The lack of enough insulin makes it harder for your body to use glucose for energy. If your body can't get glucose from your blood, it breaks down fats to supply energy to your cells. When this happens, ketones, which are more acidic than normal blood tissues, acquire in the blood. When more ketones are produced than your kidneys can handle, excess ketones build up in the blood. Your disease is most likely Type 1 if you develop diabetes before age 35, are lean, have a family history of diabetes treated with insulin and need insulin injections. Further tests may be done to approve the diagnosis. These tests include measuring islet-cell antibodies ( the antibodies directed to destroying the islet cells ), C-peptide level ( a measurement of the quantity of insulin being manufactured by the body ), and urine ketones.

If you have type 1 diabetes, you most likely will require insulin to regulate your glucose. However the occasional person in the earliest stages of type 1 may still have some islet cells left that secrete enough insulin so that insulin injections are not yet confirmed. Still, because the person has type 1 diabetes, their white blood cells are still attacking their islets cells, and the insulin-making beta cells are slowly being demolished. Ongoing controlled trials are currently having a look at using injections of little dose of insulin early in this diagnosis phase as a sort of decoy. It is thought the white blood cells will be distracted by the foreign insulin, taking them off the attack of the islet cells and therefore conserving insulin production in the body for a longer period.

Diabetic patients have always been worried by possible straightforward diabetes control measures which will enable them get on with their life.

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Type 1 Diabetes May Have a New Foe

A drug commonly used to treat non-Hodgkin's lymphoma and rheumatoid arthritis now also shows some promise in helping patients newly diagnosed with type 1 diabetes.

The drug, rituximab (Rituxan), helped patients keep producing some of their own insulin, even though the disease had destroyed some of their pancreatic beta cells, which produce the critical hormone, reports a study in the Nov. 26 issue of the New England Journal of Medicine.

The results were on par with those seen in other studies trying experimental immune therapies for type 1 diabetes, said study lead author Dr. Mark D. Pescovitz, professor of surgery and of microbiology/immunology at Indiana University in Indianapolis.

But the findings have to be interpreted with a "little caution," warned Dr. Vivian Fonseca, professor of internal medicine at Texas A&M Health Science Center College of Medicine and director of the Diabetes Institute at Scott & White in Temple.

"This paper doesn't appear as if this is a cure for diabetes. Patients did manage to produce more insulin themselves, but it's not a huge amount more. The insulin dose they used was a little bit less but not hugely less," he continued. "Even with this data, we're a long, long way from getting approval for using this kind of treatment. Also, the patients in the study were newly diagnosed so there is virtually no application for people who have had type 1 diabetes for some time."

But needing less outside insulin does have advantages. "We know that people who produce some of their own insulin tend to have less complications in the long term," Fonseca said. Those complications can include blindness and heart trouble, although in no way do researchers yet know if rituximab will reduce those problems in type 1 diabetics over the long-term.

Type 1 diabetes is an autoimmune disease in which the body's own immune system destroys the critical insulin-producing beta cells of the pancreas.

"People have been trying to change the immune system to treat type 1 diabetes, the rationale being that it's an autoimmune disease where you get antibodies that destroy the cells in the pancreas that produce insulin," Fonseca explained.

Up to now, much research has focused on the immune cells known as T-lymphocytes, the immune cells that attack the pancreas, but there has been increasing speculation that another type of cell, called B-lymphocytes, may also play a role. B cells work a step back in the process, stimulating the T cells to do their damage, Pescovitz explained. Rituximab targets B-lymphocytes.

"This deals with a whole new clinical pathway to try to deal with type 1 diabetes," he said.

In this phase 2 trial, 87 patients with newly diagnosed type 1 diabetes were randomly assigned to receive rituximab infusions or a placebo at one-week intervals for four weeks.

After one year, C-peptide levels -- an indicator of how much insulin is being produced by the body -- were higher in people taking rituximab versus those in the placebo group.

Those in the rituximab group also needed less external insulin and had fewer B cells.

Side effects faded with time, although Pescovitz pointed out that long-term adverse effects from rituximab are not yet known.

It's also not clear if this treatment would be superior to other immunosuppressive strategies, but it is certainly easier to deliver, he said.

"This [B cell] approach is all done as an outpatient basis whereas the [other agents] are done as inpatients," said Pescovitz.

And treatment over only three weeks gave a response that lasted a year, Fonseca noted.

Next, researchers need to determine if additional infusions over time will confer added benefits, and they also plan to look into ways to help the beta cells actually grow back or ways to transplant beta cells.

The study was funded by the U.S. National Institutes of Health, the Juvenile Diabetes Research Foundation International and the American Diabetes Association. Genentech and Biogen Idec, which make rituximab, provided the medication for the trial.

More information

There's more on type 1 diabetes at the Juvenile Diabetes Research Foundation

Genetic irregularity linked to Type-1 diabetes

Scientists have discovered a tiny genetic irregularity that boosts the expression of a key gene which may lead to the development of Type-1 diabetes.

Type-1 diabetes is an autoimmune disease, where the body attacks and destroys its own

insulin-producing cells. A serious illness, leading to many complications, it often starts in childhood or teenage years.

While there is no cure yet, prevention therapies are on the horizon, making the development of reliable screening tools critical. And that's where the current finding has promise.

Doctoral student Helen McGuire and Cecile King from Garvan Institute of Medical Research (GIMR) isolated the irregular DNA from mice that spontaneously develop Type 1 diabetes.

They also demonstrated that it increases production of very high levels of the immune stimulating molecule interleukin 21 (IL-21), according to a GIMR release.

The genetic irregularity occurs in the 'promoter region' of the IL-21 gene. In the world of genetics, the promoter region operates like the fuse on a bomb. In the same way as you need to light the fuse to set off a bomb, you need to activate the promoter region to activate a gene.

"Our study demonstrates that a small defect in the IL-21 promoter region is associated with the development of Type 1 diabetes in this model," said project leader King.

Their findings were published in the Proceedings of the National Academy of Sciences (PNAS).