October 2014 - Diabetes Research Connection

Diabetes Research News
October 27, 2014

Mad Scientists and Their Diabetes Breakthroughs

Imagine popping a pill covered in tiny steel needles – that you cannot in any way feel – to quickly and effectively lower your blood glucose.

Or swallowing a glucose-lowering capsule that’s only activated when you shine a blue LED light on your stomach.

We are not making this stuff up. Even though the concepts sound like top tags for the proverbial Diabetes Wall of Weird, they are both actually real-life drugs currently under development and being tested in research here in the U.S. and abroad.

A Pill Covered with Needles?

First, the Microneedle Pill is being developed by a team of researchers at the Massachusetts Institute of Technology (MIT) and Massachusetts General Hospital who recently published their work in the Journal of Pharmaceutical Sciences.

They’ve created an acrylic capsule 2 centimeters long and 1 centimeter in diameter, that includes a reservoir for the insulin and is covered with hollow, stainless steel needles about 5 millimeters long. But don’t be too afraid — there’s a dissolvable coating covering the needles so they won’t be exposed while moving down into your system.

Encaptra Concept

Here’s how it would work:

You’d swallow the pill and let it travel on down your throat into the GI tract, made safe by the protective coating and apparently that part of the body doesn’t have any pain receptors, so you wouldn’t feel a thing.
Once inside your GI tract, the pH-sensitive coating on the pill would dissolve and the small microneedles would be uncovered, to inject insulin into the lining of the stomach, small intestine, and colon.
Researchers are working to make this method even safer by using needles made of degradable polymers and sugar that would break off, embed in the GI tract and continue delivering insulin as the sugar molecules disintegrate. Wait, insulin and sugar… isn’t that the D-version of creating a pill that combines fire and water?

As noted in the video, researchers have tested this first-gen microneedle pill on a handful of pigs, and the results showed the insulin was successfully delivered without any signs of tissue damage. And yes, the pigs’ blood glucose levels decreased more quickly from this insulin delivery method than when they were given traditional insulin injections.

Aside from treating diabetes, the researchers believe this method could be used for any treatment that now requires injections — making it potentially “revolutionary.”

This research has gotten a good amount of media attention in the past few weeks; we couldn’t help rolling our eyes at the way MIT’s own press release preempted the inevitable sensational media headlines by clamoring: “New drug-delivery capsule may replace injections.”

Yes, we’d prefer to do away with shots, but the idea of swallowing needles (no matter how small) still seems a little scary, no? Especially when you see the images, like this one courtesy of the MIT press folks:

Ugh… that pill looks pretty Halloween from where I sit. What if the protective coating over the needles dissolves too quickly and it snags in someone’s throat? Or what if one of those little needles breaks off too early and gets caught somewhere… else?

Can’t help mulling over that point.

‘Just Flick the Lightswitch’ Pill?

The second new drug from the Weird Wall is an oral agent aimed at type 2 PWDs (people with diabetes) that only works when you shine a light on your stomach. So nothing scary, but definitely a little out there…

In a study published on Oct. 14 in Nature Communications, a group of international researchers explain their prototype known as JB253, a “photoswitchable sulfonylurea” that would kick-start insulin release from the T2 pancreatic cells when exposed to blue light. The authors are Dr. David Hodson and Professor Guy Rutter at Imperial College London, and Professor Dirk Traunerand Dr. Johannes Broichhagen at LMU Munich.

It’s a capsule that looks just like any other pill you would take with a meal and let dive deep down into your stomach. And in your body, it actually works to lower glucose in the same way as existing sulfonylureas drugs, widely used to treat T2 diabetes. Except that this one doesn’t do anything at first. Not until you shine a blue LED light on your abdomen (that may be adhered to your skin using adhesive, like a small non-invasive sensor), activating the pill and changing its shape inside you to turn on the glucose-lowering capability. And the light activation would be reversible, so you could easily switch off the light and stop the medication from doing its thing.

Wait, like a Kmart blue light?? Well, it’s actually violet-blue, the form of light needed to penetrate the skin, and only a very small amount of light is needed to activate the drug, researchers say.

As explained in this in-depth article in the Diabetes News Journal, the big advantage over existing sulfonylureas is that this new, light-activated delivery method would lower the risk of these meds causing hypoglycemia and even cardiovascular risk,.

Just like the microneedle-pill scientists, these researchers believe they may be on to the Next Big Thing in Medicine — light-activated meds that could lead to a safer, more controllable version of therapy for a number of illnesses.

“The idea is that light-sensitive drugs could be administered in the form of a pill, then released or activated by irradiating a patch of skin with a blue LED. When the light is switched off the drug flips back into the inactive form… Light can be controlled with exquisite precision, which allows us to target the receptor of interest with very high specificity. In addition, the activating reaction is itself reversible,” researcher Dr. Trauner explains.

Sounds weirdly intriguing, but of course there’s nothing to do but wait and see. “We have a long way to go before it will be possible to use such a therapy in patients,” researcher Dr. Hodson admits.

OK, maybe one thing we CAN do is appreciate these seemingly Mad Scientists who are willing to go out on limb for the sake of a promising idea. Seriously, today’s CGMs would have probably seemed just as “out there” to the PWDs of yesteryear…

Learn More +

Diabetes Research News
October 22, 2014

Type 1 Diabetes Discovery: Stem Cells Make Millions of Human Insulin Cells

As we are all aware, type 1 diabetes is an autoimmune disease where the body destroys insulin-producing beta cells in the pancreas. Without insulin, the body cannot control glucose, which can lead to high levels of blood sugar that eventually damage tissues and organs. A new study exposes how scientists successfully created billions of insulin-producing pancreatic beta cells from embryonic stem cells.(1)

The Harvard stem cell researchers report how they transplanted the stem cell-derived beta cells into the kidney of a diabetic mouse that showed no signs of the disease after two weeks. The study is a huge advance for patients with type 1 diabetes, and some with type 2 diabetes, many who require daily injections of insulin.

For their new technique to work in people with type 1 diabetes, the researchers must create a mechanism that halts a recipient’s immune system from attacking and destroying the 150 million or so beta cells they would receive. The team is currently collaborating with colleagues at the Massachusetts Institute of Technology (MIT) to develop an implant that protects the stem cell-derived beta cells from immune attack.

With human embryonic stem cells as a starting point, the scientists were able to produce, in the massive quantities needed for cell transplantation and pharmaceutical purposes, human insulin-producing beta cells that are equivalent in almost every way to normally functioning beta cells.(3) This is the first time this has been done.

The stem-cell-derived beta cells are currently undergoing trials in animal models, including non-human primates. Researchers have attempted to generate human pancreatic beta cells that could be cultured under conditions where they produce insulin. Cell transplantation as a treatment for diabetes is still experimental, using cells from cadavers, requiring the use of powerful immunosuppressive drugs, and having been available to only a small number of patients.

Richard A. Insel, chief scientific officer of JDRF, formerly known as the Juvenile Diabetes Research Foundation, said, “JDRF is thrilled with this advancement toward large-scale production of mature, functional human beta cells by Dr. Melton and his team. This significant accomplishment has the potential to serve as a cell source for islet replacement in people with type 1 diabetes, and may provide a resource for discovery of beta-cell therapies that promote survival or regeneration of beta cells and development of screening biomarkers to monitor beta cell health and survival to guide therapeutic strategies for all stages of the disease.”(4)

The work was funded by the Juvenile Diabetes Research Foundation, the Harvard Stem Cell Institute, the National Institutes of Health, the JPB Foundation, and Mike and Amy Barry.(4)

Learn More +

Diabetes Research News
October 18, 2014

Is Diabetes All in Your Head?

Researchers at Mount Sinai have identified a key mechanism behind diabetes that may start in the brain

Set of molecules found to link insulin resistance in the brain to diabetes

Does Diabetes Start in the Brain?

A key mechanism behind diabetes may start in the brain, with early signs of the disease detectable through rising levels of molecules not previously linked to insulin signaling, according to a study led by researchers at the Icahn School of Medicine at Mount Sinai published today in the journal Cell Metabolism.

Past studies had found that levels of a key set of protein building blocks, branched-chain amino acids (BCAAs), are higher in obese and diabetic patient, and that this rise occurs many years before someone develops diabetes. Why and how BCAA breakdown may be impaired in diabetes and obesity remained unclear going into the current study.

“Our study results demonstrate for the first time that insulin signaling in the mammalian brain regulates BCAA levels by increasing BCAA breakdown in the liver,” said Dr. Christoph Buettner, MD, PhD, Associate Professor of Medicine at the Icahn School of Medicine and senior author of the new study.

“This suggests that elevated plasma BCAAs are a reflection of impaired brain insulin signaling in obese and diabetic individuals.”

“What’s important is that rodents with impaired insulin signaling exclusively in the brain have elevated plasma BCAA levels and impaired BCAA breakdown in liver,” said Dr. Andrew C. Shin, PhD, an Instructor of Medicine at the Icahn School of Medicine at Mount Sinai and the first author of this study. “Since disrupted brain insulin signaling may cause the early rise of BCAAs seen in persons who eventually develop diabetes, the insulin resistance that leads to diabetes may actually start in the brain.”

“The results suggest that levels of BCAAs may prove to reflect brain insulin sensitivity,” Dr. Shin added. Dr. Shin also pointed out that the team’s newly discovered pathway is also found in organisms ranging from humans to rodents to worms. Mechanisms “conserved” across evolution are often of fundamental biological importance.

The initial discovery that started this line of investigation was made after proteomic and metabolomic studies of liver and plasma from rats that had been infused with insulin into the brain pointed toward a role of brain insulin signaling in BCAA catabolism. “Our study provides an example of how proteomics and metabolomics, techniques that survey proteins and metabolites allow researchers to come up with a hypothesis. They are also great discovery tools,” said Dr. Buettner.

The team then went on to test the concept in a variety of animal models such as mice, rats, and round worms. They were also able to confirm in prediabetic monkeys as well as obese and diabetic humans that elevated BCAAs are associated with decreased BCAA breakdown in liver.

This study was conducted through partnerships with Pacific Northwest National Laboratory, Pennsylvania State University College of Medicine, Duke University Medical Center, University of Ulm, University Medical Center Hamburg-Eppendorf and Oregon National Primate Research Center.

The study was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to Drs. Shin and Dr. Buettner and the American Diabetes Association to Dr. Buettner.

About the Mount Sinai Health System

The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven member hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services—from community-based facilities to tertiary and quaternary care. The System includes approximately 6,600 primary and specialty care physicians, 12-minority-owned free-standing ambulatory surgery centers, over 45 ambulatory practices throughout the five boroughs of New York City, Westchester, and Long Island, as well as 31 affiliated community health centers. Physicians are affiliated with the Icahn School of Medicine at Mount Sinai, which is ranked among the top 20 medical schools both in National Institutes of Health funding and by U.S. News & World Report.

For more information, visit Mount Sinai, or find Mount Sinai on Facebook, Twitter and YouTube.
Contact:
Mount Sinai Press Office
newsmedia@mssm.edu
212-241-9200
The Mount Sinai Hospital / Mount Sinai School of Medicine
@mountsinainyc

Learn More +

Diabetes Research News
October 14, 2014

Long Acting Insulin Versus Immediate Acting Insulin for Type 1 Diabetes Patients Compared in Review

For many people Long acting insulin with type 1 diabetes, daily treatment and management of the condition is a big part of their life. But is one form of treatment better than others?

A new review explored long-acting insulin in the treatment of type 1 diabetes. The researchers found evidence that this treatment method was more effective at controlling type 1 diabetes than immediate-acting insulin. They also found that long-acting insulin was tied to fewer safety concerns, including weight gain and severe diabetic episodes.

In type 1 diabetes, which is often diagnosed during youth, the body doesn’t produce insulin — a hormone that helps turn sugar into energy — causing issues with blood sugar levels. Because the body of type 1 diabetes patients doesn’t produce insulin, insulin therapy is required.

According to the authors of this study, which was led by Andrea C. Tricco, PhD, of the Li Ka Shing Knowledge Institute at St. Michael’s Hospital in Ontario, Canada, some have suggested that newer, long-acting insulin treatments (like glargine and detemir) might be better than immediate-acting versions of insulin therapy (like Neutral Protamine Hagedorn).

To explore the topic, Dr. Tricco and team identified 39 studies comparing the two insulin therapy methods in 7,496 adult type 1 diabetes patients.

In reviewing the studies, the researchers found that long-acting methods were slightly more effective at reducing glycosylated hemoglobin (A1C) levels — a measure of average blood sugar levels over several months.

The patients on long-acting insulin also gained less weight and were less likely to experience severe hypoglycemia — when blood sugar drops so low that medical attention is required.

When looking at cost-effectiveness, the majority of studies found that long-acting insulin was more expensive, but more effective.

“Patients and their physicians should tailor their choice of insulin according to preference, cost and accessibility,” wrote the review authors.

It is important to note that these findings were based on a review of previous studies. Dr. Tricco and team noted that further research comparing long-acting and immediate-acting insulin treatment options is needed.

This study was published October 1 in The BMJ.

Funding for the study was provided by the Canadian Institutes for Health Research/Drug Safety and Effectiveness Network (CIHR/DSEN). No conflicts of interest were reported.

Citation:

The BMJ, “Safety, effectiveness, and cost-effectiveness of long-acting versus intermediate-acting insulin for patients with type 1 diabetes: a systematic review and network meta-analysis”

Last Updated:

October 1, 2014

Source:

dailyrx.com

Learn More +

DRC & Research News
October 11, 2014

A New Approach to Diabetes Discovery

Welcome to the Diabetes Research Connection, the first nonprofit to use crowd funding to enable innovative diabetes investigations.

We give early-career researchers the opportunity to innovate in an environment where conventional research continues to win most of the available government funding. We give people affected by diabetes an opportunity to make a uniquely personal impact in the fight against this disease.
We use the expertise of more than 70 top diabetes researchers to assure that projects approved are MERITORIOUS and INNOVATIVE.
We have no employees, so our overhead is minimal. Donations go to science, not operations.
We publish ALL research results, because they add to our body of knowledge.
Donors can choose the research projects they wish to support. Not only do donors know EXACTLY where their contribution is going, they can follow the scientist’s progress throughout the investigation.

Imagine being in on the ground floor of a major discovery!

Learn More +

DRC & Research News
October 10, 2014

Novel Diabetes Research

The Diabetes Research Connection is pleased to present THREE extraordinary research projects. Scientists from the University of Florida, University of Washington, and University of Michigan seek your support in order to pursue novel investigations into a cure for diabetes.