Type 1 Diabetes Reversed in Mice

Type 1 diabetes accounts for about 5% of all diabetes and is usually diagnosed in young people. There is no cure for the disease - which happens when the immune system destroys pancreatic beta cells and the body's only source of insulin, a hormone that controls blood sugar. Now researchers report they have successfully tested a new therapy that appears to reverse new onset type 1 diabetes in mice.

Investigators from the University of Cincinnati (UC) presented their findings at the 74th Scientific Sessions of the American Diabetes Association in San Francisco on 14 June 2014.

There are two parts to the immune system: the innate immune system, which we are born with and attempts to fight infection straight away; and the adaptive immune system, which takes time to mount a response that is more specific to the particular pathogen.

The innate immune system includes a group of cells known as dendritic cells that send messages to the adaptive immune system. Dendritic cells are important antigen processors - they have receptors on their cell surface that react to pathogens and present their antigens to the adaptive immune cells such as immature T cells to develop a more precise response.

Most previous attempts to combat type 1 diabetes have aimed at reducing an overzealous adaptive immune response by eliminating the auto-reactive T cells directly. But in this new study, the researchers used an approach that tackles T cells indirectly, as study leader William Ridgway, a professor in medicine at UC, explains:

"We are targeting a receptor that is found mostly on the innate immune cells, such as dendritic cells."

He and his team decided to tackle a receptor on dendritic cells called TLR4. Previous studies have already established that non-obese diabetic mice have faulty innate immune cells, and that this could be partly due to a defect in TLR4, which many suspect helps to prevent type 1 diabetes when it functions normally.

Antibody that boosts TLR4 reversed new onset type 1 diabetes in mice

The researchers found when they used an agonistic monoclonal antibody, UT18, to boost the activity of TLR4 in mice with new onset type 1 diabetes, it reversed the disease in a high percentage of them.

While the TLR4 pathway in humans is similar to that of mice, there are some differences, so further study is required to see if the treatment will work in humans.

Prof. Ridgway says the cause of the reversal was the "preservation of the endocrine pancreatic beta cells that produce insulin. These cells are preserved from the autoimmune attack which is the hallmark of Type 1 diabetes."

He points out that the key to reversing type 1 diabetes in the mice was catching the disease right at the onset, which has only a very short time window. The window is likely to be longer in humans, he says, but it is still relatively short before end-stage type 1 diabetes sets in.

While the TLR4 pathway in humans is similar to that of mice, there are some differences, so further study is required to see if the treatment will work in humans.

Prof. Ridgway says there is also a chance, if the therapy works in humans, that it will do so with an agonistic anti-TLR4 agent that is already approved, or under development.

Meanwhile, Medical News Today reported on another study presented at the same conference by researchers from the Intermountain Heart Institute at Intermountain Medical Center in Murray, UT. The Intermountain study explains how type 2 diabetes risk in prediabetics may be combated by periodic fasting to work against the effects of insulin resistance.

Written by Catharine Paddock PhD

source : http://www.medicalnewstoday.com/articles/278289.php

Periodic Fasting may protect against Diabetes in At-Risk Groups

At the 2014 American Diabetes Association Scientific Sessions in San Francisco, CA, researchers present new findings on how diabetes risk in prediabetics may be combated by periodic fasting.

In people who have prediabetes, the amount of glucose in the blood is higher than normal but is not high enough to be classed as diabetes.

In 2011, researchers at the Intermountain Heart Institute at Intermountain Medical Center in Murray, UT, investigated how glucose levels and weight were effected by 1 day of water-only fasting in healthy people.

"When we studied the effects of fasting in apparently healthy people, cholesterol levels increased during the one-time 24-hour fast," says Benjamin Horne, PhD, director of cardiovascular and genetic epidemiology at the Intermountain Medical Center Heart Institute and lead researcher on the new study.

"The changes that were most interesting or unexpected were all related to metabolic health and diabetes risk," he adds.

"Together with our prior studies that showed decades of routine fasting was associated with a lower risk of diabetes and coronary artery disease, this led us to think that fasting is most impactful for reducing the risk of diabetes and related metabolic problems."

Consequently, Dr. Horne and team began investigating the effects of fasting in prediabetics. Although Medical News Today does not have details on the number of participants included in the new study, the team has revealed that participants were between the ages of 30 and 69, and each subject also had at least three metabolic risk factors, such as:

• A large waistline
• A high triglyceride level
• A low HDL cholesterol level
• High blood pressure
• High fasting blood sugar.

Body 'feasts' on bad cholesterol in fat cells, negating insulin resistance effects

The researchers found that during fasting days, the participants' cholesterol went up slightly, as it had done in the previous study of healthy people. However, over a 6-week period, the cholesterol levels of the prediabetic participants actually decreased by about 12%.

"Because we expect that the cholesterol was used for energy during the fasting episodes and likely came from fat cells," says Dr. Horne, "this leads us to believe fasting may be an effective diabetes intervention."

After 10-12 hours of fasting, the body begins to scavenge other sources of energy throughout the body in order to sustain itself. The benefit to prediabetics, Dr. Horne's team believes, is that because the body feasts on the LDL (or "bad") cholesterol in fat cells it negates the effect of insulin resistance.

Insulin resistance is when insulin production becomes so high that the pancreas can no longer produce the body's required levels of insulin, which causes blood sugar to rise. The researchers believe fasting may prevent this.

Insulin resistance is when insulin production becomes so high that the pancreas can no longer produce the body's required levels of insulin, which causes blood sugar to rise.

"The fat cells themselves are a major contributor to insulin resistance, which can lead to diabetes," Dr. Horne explains. "Because fasting may help to eliminate and break down fat cells, insulin resistance may be frustrated by fasting."

Although fasting may protect against diabetes, Dr. Horne reminds that it is important to keep in mind that fasting did not achieve overnight results. He adds that more in-depth study is needed to define what the optimum length and frequency of fasting should be in prediabetics.

"Fasting has the potential to become an important diabetes intervention," he says. "Though we've studied fasting and its health benefits for years, we didn't know why fasting could provide the health benefits we observed related to the risk of diabetes."

Recently, Medical News Today reported on a study conducted by the University of Southern California in Los Angeles that suggested prolonged fasting may "reboot" the immune system - protecting against the toxic effects of chemotherapy and triggering stem cell regeneration of new immune cells, as well as clearing out old and damaged cells.

Written by David McNamee

source : http://www.medicalnewstoday.com/articles/278264.php