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Diabetes Research News
May 19, 2020

Could Insulin-Producing Beta Cells Play a Role in Triggering Onset of Type 1 Diabetes?

Researchers know that type 1 diabetes (T1D) occurs when the immune system mistakenly attacks and destroys insulin-producing beta cells. This leaves the body unable to self-regulate blood glucose levels because it produces little or no insulin on its own. What scientists have been striving to understand is what causes the body to destroy these cells in the first place.

A recent study found that the beta cells themselves may play a role in signaling the attack. The insulin-producing cells may be sending out signals that increase M1 macrophages that cause inflammation and the resulting cell destruction. The M2 macrophages that reduce inflammation and help repair tissue are not as heavily expressed.

The researchers looked specifically at Ca2+-independent phospholipase A2beta (iPLA2beta) enzymes and the resulting iPLA2beta-derived lipids (idles) and how they are activated by beta cells. The idols either stimulate M1 macrophages or M2 macrophages depending on the active signaling pathways.

The study involved two sets of mice – one group that had no iPLA2beta expression (knockout mice), and one group with overexpression of iPLA2beta. Researchers found that even when M1 macrophage activation was induced, the knockout mice experienced an increase in M2 macrophages and a reduced inflammatory state. The mice that had overexpression of iPLA2beta, on the other hand, experience an increase in M1 macrophages and inflammatory eicosanoids.

According to Sasanka Ramanadham, Ph.D., research co-lead, “To our knowledge, this is the first demonstration of lipid signaling generated by beta cells having an impact on an immune cell that elicits inflammatory consequences. We think lipids generated by beta cells can cause the cells’ own death.”

As scientists continue to learn more about lipid signaling and the potential role it plays in the development of type 1 diabetes, this could lead to improved methods of delaying or preventing onset or progression of the disease. This is yet another approach that researchers are taking to understand as much as they can about how and why T1D develops and how to better manage the disease.

It is this type of research that opens doors to advancements toward preventing or curing type 1 diabetes. Diabetes Research Connection (DRC) supports early-career scientists pursuing novel, peer-reviewed research studies focused on improving diagnosis, treatment, and prevention of T1D as well as improving quality of life for individuals living with the disease and one day finding a cure. Ensuring researchers receive necessary funding for their projects is critical. To learn more about current projects and support these efforts, visit https://diabetesresearchconnection.org.

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Diabetes Research News
May 14, 2020

Redifferentiating Beta Cells to Treat Type 1 Diabetes

All cells serve a specific purpose, and each one plays an integral role in the function and survival of the human body. However, in individuals with type 1 diabetes, insulin-producing beta cells are destroyed leaving the body unable to self-manage glucose levels. Scientists have been trying to determine exactly why this occurs, and how to stop, prevent, or reverse it for years. Each day they learn a little more.

A recent study out of Germany examines dedifferentiation of beta cells as a potential cause for type 1 diabetes. Researchers believe that insulin-producing beta cells may lose their identity, which in turns causes a regression in function. They sought to target the affected cells using diabetic mouse models to see if they could redifferentiate the beta cells back to normal function, or at least preserve existing function if regression is caught early.

To do this, they invoked diabetes in mice using streptozotocin but left some functional beta cells. Then, they administered a combination of Glucagon-like peptide-1 (GLP-1) and estrogen in conjunction with long-acting insulin. The drug was directed to the dedifferentiated beta cells, and results showed that this combination treatment helped to “normalize glycemia, glucose tolerance, to increase pancreatic insulin content and to increase the number of beta cells.” They also found that when GLP-1/estrogen was used together, rather than each substance on its own, human beta cells also showed improved function.

The mice in the study showed no signs of systemic toxicity even when high doses of the drug were administered. This could help to ease the way when the treatment is ready to be used in human trials. Researchers want to further explore whether this treatment could be used as a form of regenerative therapy to redifferentiate dedifferentiated beta cells and stimulate insulin production. If type 1 diabetes was detected early on, the therapy could potentially be used to slow or stop cell regression.

This study could change the way that some researchers approach their work and inspire new studies aimed at treating or curing type 1 diabetes. Diabetes Research Connection (DRC) supports early-career scientists in pursuing this type of work by providing necessary financial resources. With proper funding, scientists can move forward with their projects and improve not only understanding of the disease, but also treatment options. The goal is to one day discover a cure. To learn more about current projects and how to help, visit https://diabetesresearchconnection.org.

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Diabetes Research News
May 12, 2020

New Oral Treatment May Help with Managing HbA1c for Type 1 Diabetes

Keeping HbA1c levels within a healthy range can be challenging for those living with type 1 diabetes. It requires constant vigilance when it comes to monitoring blood sugar levels and administering the appropriate amount of insulin. Even with careful management, there can be complications.

A recent study found that a once-daily pill used in conjunction with insulin may help reduce HbA1c levels by as much as 0.32% after 12 weeks. The pill, known as TTP399, activates glucokinase in the liver. This, in turn, stimulates the body to improve glucose utilization which can lead to lower blood glucose levels. Overall, this could help improve HbA1c levels as well as time spent within a healthy glucose range.

A randomized, double-blind, adaptive study compared participants taking the TTP399 pill versus those on a placebo. Those who received the pill showed improved glucose response and fewer symptomatic hypoglycemic episodes. The average improvement in HbA1c was 0.21%, and there was also an average of an 11% reduction in the dosage amount of total daily mealtime bolus insulin needed.

On the other hand, the placebo group showed a 0.11% increase in HbA1c after the 12-week trial period. Neither group reported any incidences of diabetic ketoacidosis, and there was only one incident of severe hypoglycemia, which occurred in the placebo group.

This phase 2 study involved 85 participants. They were all currently either administering daily injections or using an insulin pump. If they were using a continuous glucose monitor (CGM), they had to be on it for at least three months prior to the start of the study to be included.

According to Steve Holcomb, president and CEO of vTv Therapeutics, “Consistent with FDA guidance, a 0.3% improvement in HbA1c is considered clinically meaningful and coupled with the well-controlled population of patients and favorable safety data from our clinical trials to date, this provides a strong basis for moving this potential first-in-class program forward.”

The pill could be used in conjunction with insulin therapy as a way of further managing and reducing HbA1c levels. This an exciting step forward in terms of type 1 diabetes management and supporting individuals in staying within healthy ranges for HbA1c and daily blood sugar levels.

Diabetes Research Connection (DRC), though not involved with this study, is interested to see how it evolves moving forward, and what it could mean for the future of oral treatment involving noninsulin products.

Research for type 1 diabetes continues to improve and advance every single day, and DRC helps makes this possible by providing critical funding to early-career scientists pursuing novel research studies on type 1 diabetes. Through generous donations from individuals, corporations, and foundations, they are able to provide researchers with up to $50K in funding to support studies aimed at improving prevention measures, enhancing quality of life, reducing complications, and finding a cure. Learn more by visiting https://diabetesresearchconnection.org.

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Diabetes Research News
April 21, 2020

Investigating a New Form of Diabetes Management – a Smart Patch

The traditional method of managing type 1 diabetes is testing blood sugar levels, then dosing and administering the correct amount of insulin to keep blood sugar within the target range. This is done over and over again throughout the day, each and every day. Researchers are constantly seeking improved methods of managing the disease that are less patient intensive.

Over the years, scientists have created continuous glucose monitors, insulin pumps, artificial pancreases, and other systems to assist with managing type 1 diabetes (T1D). Each device has its pros and cons depending on the patient and their situation. Patients must find what works best for their needs.

A recent study is investigating yet another treatment option: a smart insulin patch. This small patch contains tiny microneedles with glucose-sensing polymer. When blood sugar begins to rise, the polymer is activated and releases doses of insulin. As blood-glucose levels return to normal, it stops administering insulin.

This technology removes the burden of constantly testing blood by patients and handles the testing and administration on its own. The needles penetrate the skin just far enough to be effective without causing much more than a pinprick of pain. The current model is designed to manage blood sugar levels for up to 24 hours and has been tested on mice and pigs. After 24 hours, the patch would need to be replaced with a fresh one.

Researchers are in the process of obtaining approval to begin human trials for the smart insulin patch. Although it may be several years before this technology could potentially be brought to market, it is a step in the right direction toward creating a more effective, efficient way of managing T1D. Researchers also believe that it may help reduce risk of insulin overdoses which can lead to hypoglycemia.

Though not involved with this study, Diabetes Research Connection (DRC) is excited to see what happens in the future if the patch is approved for human trials. It has the potential to become one more tool for individuals with T1D to use to manage the disease and enhance their quality of life. The DRC is committed to supporting research regarding T1D and providing funding to early career scientists for novel, peer-reviewed studies. Click to learn more about current projects and provide support.

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