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Preserving Endogenous Insulin Production

Preserving Endogenous Insulin Production in Newly Diagnosed Type 1 Diabetes Patients

A hallmark of type 1 diabetes is the body loses its ability to naturally produce enough (or any) insulin to effectively manage blood glucose levels. This is due to the mistaken destruction of insulin-producing beta cells by the immune system, a process that researchers are continually learning more about. In many cases, when type 1 diabetes (T1D) is first diagnosed, there is a short window of time (up to about six months) where the body still creates insulin, but not enough to meet demand.

A recent study explored a new way to try to preserve endogenous insulin production and reduce the amount of insulin newly diagnosed patients required. The study involved 84 patients ages 6 to 21 who had been diagnosed with T1D within 100 days of the start of the trial. Approximately two-thirds of participants were given the drug golimumab, while the other one-third received a placebo. Golimumab is an anti-tumor-necrosis-factor (TNF) therapy that is already approved by the Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis, ulcerative colitis, and other autoimmune conditions. It has not yet been approved for use in patients with T1D.

The patients who received golimumab self-administered the drug via injection every two weeks. Results showed that these patients achieved markedly better glycemic control that patients receiving the placebo. After 52 weeks of treatment, “41.4% of participants receiving golimumab had an increase or less than 5% decrease in C-peptide compared to only 10.7% in the placebo group.”

Furthermore, patients who were still in the “honeymoon phase” of their diabetes, or the first 3-6 months after diagnosis where there is still some endogenous insulin production and not as much injected insulin is needed, also showed improvement once transitioning out this phase and continuing to take golimumab. Those patients showed a smaller increase in injected insulin than the placebo group requiring just 0.07 units per kilogram more per day versus 0.24 units per kilogram per day respectively. Another notable improvement is that patients between the ages of 6 and 18 experienced 36% fewer episodes of level 2 hypoglycemia, a condition that can be potentially life-threatening and negatively impact the quality of life.

Since golimumab is already FDA-approved for other conditions, these phase 2 study results play an important role in moving the process forward to show that it may be an effective treatment for T1D as well. This therapy may be able to help newly diagnosed patients retain some of their body’s natural insulin-producing abilities and decrease the amount of injected insulin needed to maintain good glycemic control.

Golimumab may become another option for patients with type 1 diabetes in the future and change how the disease is managed when caught and treated early on. It is encouraging to see new ways to preserve beta-cell function. Diabetes Research Connection (DRC) is interested to see how this study unfolds and whether golimumab is approved for the treatment of type 1 diabetes.

Although not involved in this study, DRC supports early-career scientists in pursuing studies like these and other projects related to preventing and curing T1D as well as minimizing complications and improving the quality of life for individuals living with the disease. Scientists can receive up to $50K in funding to advance their research. To learn more about current projects and support these efforts, visit https://diabetesresearchconnection.org.

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Study Affirms Safety and Effectiveness of U.S. Insulin Products

When an individual with type 1 diabetes (T1D) administers insulin to control their blood sugar levels, they want to feel confident that no matter what U.S. retail pharmacy they purchased their insulin from, it will work. Differences in consistency and potency of insulin could have a detrimental impact on patient health and their ability to manage their T1D.

A recent study looked at samples of human and analog insulin products from across manufacturers and found that they were all correctly labeled and contained the expected quantity of active insulin. Since individuals with T1D rely on insulin injections multiple times per day, it can be reassuring to know that the product they are using adheres to how it is labeled.

The study was a joint effort between JDRF, the American Diabetes Association (ADA), and the Leona M. and Harry B. Helmsley Charitable Trust. The study was conducted within a single year, so now the team is looking to expand to a second phase that measures for any variations again, this time looking at “potential seasonal variations in reported insulin activity.”

Diabetes Research Connection (DRC) is proud to see that manufacturers are producing quality insulin products that meet consistency and potency standards. Worrying about the quality of their insulin is not something that individuals with T1D should have to do. The DRC supports early-career scientists in pursuing novel, peer-reviewed research focused on the prevention and cure of type 1 diabetes as well as minimizing complications and improving quality of life for individuals living with the disease. To learn more, visit https://diabetesresearchconnection.org.

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Combination Therapy May Help Improve Blood Sugar Management

Maintaining stable blood sugar levels and minimizing complications is a constant challenge for many individuals living with type 1 diabetes. They must always be alert to whether their blood sugar is too low or too high and how much insulin to administer. However, researchers are continually exploring ways to improve blood sugar management by better understanding how diabetes affects the body.

In a recent study, researchers from Stanford University have taken a new approach by combining two FDA-approved drugs and developing a way for them to work in tandem as they naturally do in the body through a single injection. In addition to insulin, individuals with type 1 diabetes (T1D) would also take a drug based on the hormone amylin. This drug is already FDA-approved, but less than 1% of patients with diabetes take it. This could be because they do not want to administer a second shot every time they take insulin. When combined, insulin and the amylin-based drug work together just as they do when naturally occurring in the body. Amylin is produced by the same insulin-producing beta cells in the pancreas.

According to researchers, amylin works in three ways:

“First, it stops another hormone, glucagon, from telling the body to release additional sugar that has been stored in the liver. Second, it produces a sense of “fullness” at mealtimes that reduces food intake. Third, it actually slows the uptake of food by the body, reducing the typical spike in blood sugar after a meal. All three are a boon to diabetes care.”

However, in their current states, insulin and the amylin-based drug are too unstable to combine in one syringe. To combat this problem, the researchers have developed a protective coating that encompasses each molecule individually, allowing them to stably exist together. This molecular wrapper has a Velcro-like feature that “reversibly binds to both insulin and amylin separately, shielding the unstable portion of each molecule from breakdown.” Once administered, the coating dissolves in the bloodstream.

With this protective coating – known as cucurbituril-polyethylene glycol (CB-PEG) – the combination of insulin and the amylin-based drug showed stability for at least 100 hours. This could give it a shelf life that is long enough to be used with an insulin pump. Researchers have tested the combination therapy on diabetic pigs and are working toward gaining approval for human trials. Since both drugs are already FDA-approved, this could help to move things along more quickly.

Diabetes Research Connection (DRC) is excited to see what this could mean for the future of T1D treatment and blood glucose management. This combination therapy could help alleviate some of the challenges that patients face and improve management of the disease. Though not involved with this study, the DRC is committed to supporting research around type 1 diabetes in order to improve diagnosis, treatment, prevention, and the pursuit of a cure. The organization provides critical funding to early-career scientists to advance their research. Learn more about current projects and how to support these efforts by visiting https://diabetesresearchconnection.org.

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Glucose-Sensing Neurons Work Together to Manage Blood Sugar

Whereas insulin is necessary to combat high blood glucose levels, a different hormone is necessary to manage low ones: glucagon. This hormone helps to regulate glucose production and absorption bringing glucose levels back into an acceptable range.

A recent study from researchers at Baylor University and other institutions found that there is a specific group of neurons in the brain that may play an integral role in blood sugar regulation and preventing hypoglycemia. Within the ventrolateral subdivision of the ventromedial hypothalamic nucleus region, there are estrogen receptor-alpha neurons that are also glucose-sensing.

What the researchers found particularly interesting was that half the neurons became more active when blood sugar levels were high (glucose-excited), and the other half became more active when blood sugar levels were low (glucose-inhibited). Furthermore, each group of neurons used a different ion channel to regulate neuronal firing activities. However, they both led to the same result – increasing blood glucose levels when they were low – even though they were activating different circuits in the brain. This leads to a perfect balance in managing blood sugar.

The next step in the study is to investigate whether the fact that all of the neurons in this specific group that expressed estrogen receptors play a role in the glucose-sensing process. In turn, this could lead to more gender-specific studies to determine differences in neuronal function when it comes to blood sugar regulation.

One important factor to note is that all of these studies were conducted on hypoglycemic mice. The researchers did not identify whether the process is believed to be the same in humans.

This is another step forward in better understanding how diabetes affects the body, brain, and functioning. Diabetes Research Connection strives to empower early-career scientists in pursuing novel, peer-reviewed studies related to type 1 diabetes by providing up to $50K in funding. Research is focused on the prevention and cure of type 1 diabetes as well as minimizing complications and improving quality of life for individuals living with the disease. Find out how to support these efforts by visiting https://diabetesresearchconnection.org.

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Artificial Pancreas App Supports Type 1 Diabetes Management

Maintaining good glycemic control is challenging when living with type 1 diabetes. Individuals must carefully monitor their blood glucose levels throughout the day, then administer the appropriate amount of insulin to try to stay within target range. This can be more difficult than it sounds. Furthermore, many people with type 1 diabetes struggle with their blood sugar dropping overnight while they are asleep.

Patients living in the UK may have access to a new artificial pancreas app that takes away some of the stress and burden of constant blood sugar management. The CamAPS FX app works in conjunction with the Dana RS insulin pump and the Dexcom G6 continuous glucose monitor. Using a complex algorithm, the app tracks blood glucose levels, then automatically adjusts insulin administration accordingly. This reduces the demand for regular finger sticks to check blood sugar, and patients do not need to calculate how much insulin they require on their own.

The app has been approved in the UK for individuals age one and older, including pregnant women, who have type 1 diabetes. It was developed based on 13 years of clinical research conducted by Professor Roman Hovorka from the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust and his team at the Wellcome-MRC Institute of Metabolic Science. In addition, data from the app can be shared with patients’ healthcare teams allowing them to provide more personalized diabetes care.

Technology has made some significant advancements in type 1 diabetes care, and this is one more example of how it can impact management of the disease and improve health outcomes. Artificial pancreas technology is an area that researchers have been focused on improving over the years in order to give patients more options and reduce the burden of managing the disease.

Diabetes Research Connection (DRC) is excited to see more results from use of the app and what it could mean for future diabetes management, not just in the UK but around the world. Currently the app is only available to patients at select diabetes clinics in the UK. Though not involved with this project, the DRC is committed to advancing diabetes research to help prevent and cure type 1 diabetes, minimize complications, and improve quality of life for those living with the disease. Early-career scientists can receive up to $50K in funding to support novel, peer-reviewed research projects. To learn more about current studies and contribute to these efforts, visit https://diabetesresearchconnection.org.

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Generating Pancreatic Islet Organoids to Treat Type 1 Diabetes

In individuals with type 1 diabetes, the immune system mistakenly attacks and destroys insulin-producing beta cells. Without a naturally occurring supply of insulin to manage glucose, blood-glucose levels can quickly spiral out of control leading to hypo- or hyperglycemia. If left untreated, this can become potentially fatal.

A recent study found a way to generate an abundance of pancreatic islet organoids that are glucose-responsive and insulin-secreting. As such, they can help with management and potential reversal of type 1 diabetes. Researchers identified a cluster of protein C receptor positive (Procr+) cells in the pancreas of adult mice. These cells have the ability to differentiate into alpha, beta, omega, and pancreatic polypeptide (PP) cells, with beta cells being the most abundant.

The Procr+ islet cells can then be cultured to generate a multitude of islet-like organoids. When the organoids were then be transplanted into adult diabetic mice, they were found to reverse type 1 diabetes. More research is necessary to determine if human pancreatic islets contain these same Procr+ endocrine progenitors and a similar process could be used to treat type 1 diabetes in humans.

As scientists delve deeper into the cellular impact of the disease and how different cells respond and can be manipulated, it opens new doors to potential treatments or cures for type 1 diabetes. Though not involved in this study, this is the type of cutting-edge research that the Diabetes Research Connection (DRC) is committed to supporting. Early-career scientists can receive up to $50,000 in funding through DRC for novel, peer-reviewed research aimed at preventing and curing type 1 diabetes, minimizing complications, and improving the quality of life for individuals living with the disease. To learn more and support these efforts, visit https://diabetesresearchconnection.org.

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Type 1 Diabetes and the Coronavirus (COVID-19)

Those with Type 1 Diabetes (T1D) are members of an exclusive club which is more vulnerable to the effects of the Coronavirus (COVID-19), once it is contracted. Click here to learn more. We encourage you to follow the World Health Organization’s protective recommendations.

While T1D‘s are not at a greater risk of contracting the disease, it is important to take precautionary measures. These include measuring your blood glucose levels frequently and keeping them in the normal range. This will help ensure greater resistance and a faster recovery. More frequent monitoring of ketones is critical, especially if your blood glucose is elevated due to sickness, cold therapeutics containing sugar or syrup and inactivity. Steroidal decongestants are also likely to increase your blood glucose levels. Diabetic ketoacidosis (DKA) may exhibit flu-like symptoms, which is why it is important to measure ketones with test strips available from your local pharmacy or online. Additional amounts of insulin may be required under these circumstances. Contact your physician(s) immediately if you have been exposed to the virus or have symptoms.

Be sure to stock an adequate supply (a minimum of two weeks) of all your medications. For more advice managing T1D during this pandemic, please visit: https://www.jdrf.org/coronavirus/.

For the latest updates on the global impact of COVID-19 go to: https://www.worldometers.info/coronavirus/.

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Scientists Found a Way to Generate Insulin-Producing Beta Cells

More than one million people in the United States are living with type 1 diabetes according to statistics from the Centers for Disease Control and Prevention. There is a strong push to improve management of the disease and find a cure. The more researchers learn about T1D, the more precise their prevention and treatment methods become.

A recent study reveals that improvements in stem cell therapy have reversed T1D in mice for at least nine months and, in some cases, for more than a year. One of the challenges that scientists have faced with using human pluripotent stem cells (hPSCs) is that it can be difficult to zero differentiation in one specific type of cell. Often multiple types of pancreatic cells are produced. While there may be an abundance of cells that scientists want, the infiltration of excess cells that are not needed diminishes their impact (even though they are not harmful).

Scientists at the Washington University School of Medicine in St. Louis have found a way to generate insulin-producing beta cells without creating as many irrelevant cells. Their approach focuses on the cell’s cytoskeleton, which is its inner framework. Through this process, they were able to produce vast amounts of beta cells that are able to normalize blood glucose levels.

When transplanted into severely diabetic mice (blood glucose levels above 500 mg/dL), the cells effectively reversed the effects of diabetes and brought blood sugar levels down into target range within two weeks. Normoglycemia was maintained for at least nine months.

This is a major step forward in stem cell therapy and the use of hPSCs to potentially cure diabetes one day. There is still more testing and research that needs to be done before this approach is applied to human trials.

Ongoing research is essential for finding a cure for T1D. Diabetes Research Connection supports these efforts by providing critical funding to early-career scientists pursuing novel research studies on the disease. By giving them the means to complete their projects, these researchers can continue to advance knowledge and treatment options. Learn more about current studies and how to help by visiting https://diabetesresearchconnection.org.

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Controlling Beta Cell Proliferation and Apoptosis to Manage Type 1 Diabetes

A key indicator of type 1 diabetes is lack of insulin-producing beta cells in the pancreas. These cells are mistakenly attacked and destroyed by the immune system leaving individuals unable to naturally manage their blood sugar. With little to no production of insulin, the body cannot effectively process sugars and use them as fuel. Instead, individuals must constantly monitor their blood glucose levels and administer insulin as needed.

However, a recent study uncovered how an FDA-approved drug for treating breast cancer may also be effective in diabetes care. Neratinib is a dual inhibitor of HER2 and EGFR kinases, but researchers have also found that it is incredibly effective at blocking mammalian sterile 20-like kinase 1 (MST1) as well. MST1 plays a key role in regulating beta cell proliferation and apoptosis. By inhibiting MST1 expression, insulin-producing beta cells may be protected from this process leading to greater beta cell survival and improved function.

In addition, when mouse models and human islets were treated with neratinib, they showed a marked improvement in glucose control and maintained lower overall glucose levels. The drug also restored expression of specific transcription factors such as PDX1 that contribute to glucose metabolism and insulin production.

Neratinib is an FDA-approved cancer treatment drug currently being used for breast cancer, but its effectiveness in treating other forms of cancer is being explored as well. Now researchers are examining whether its indications could be expanded to include diabetes.  While it has been proven safe in cancer treatment, scientists are looking at ways to decrease its toxicity and improve specificity for diabetes.

In its current form, neratinib does not only target MST1 – it inhibits other kinases as well. Furthermore, there is concern that an extreme decrease in beta cell apoptosis could lead to increased expression of other cell types which could impact health. However, researchers can use this study as a foundation for exploring ways in which to refine the drug and improve beta-cell protection and function while minimizing other effects.

Diabetes Research Connection (DRC) is interested to see how this study impacts future treatment and prevention efforts in regard to type 1 diabetes. The DRC provides critical funding to early career scientists pursuing novel, peer-reviewed research projects focused on prevention, treatment, and improvement of quality of life for individuals living with the disease. This support can lead to scientific breakthroughs and have a significant impact on understanding of type 1 diabetes. To learn more about current projects and how to support these efforts, visit http://diabetesresearchconnection.org.

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Leveraging the Power of Light to Manage Type 1 Diabetes

A common problem in managing type 1 diabetes is maintaining relatively stable blood glucose levels. By the time a person realizes their blood sugar is rising or falling and begins to treat it, they may already experience spikes. This can be tough on the body and lead to over- or undertreatment in an effort to curb the highs or lows. Though technology has made it faster and easier to track blood glucose levels and more accurately administer insulin, it’s still not a perfect system.

A recent study reveals that researchers may have come up with a way to manage blood sugar without manually administering insulin. They engineered pancreatic beta cells to be responsive to exposure to blue light. By introducing a photoactivatable adenylate cyclase (PAC) enzyme into the cells, they produce a molecule that increases insulin production in response to high levels of glucose in the blood.

The molecule is turned on or off by blue light and can generate two to three times the typical amount of insulin produced by cells. However, it does not boost production when glucose levels in the blood are low. Furthermore, the cells do not require more oxygen than normal cells, which helps alleviate the common issue of oxygen starvation in transplanted cells.

The study was conducted on diabetic mice, so more research is needed to determine whether the process will be as effective in humans. If it is, this could mean that individuals with type 1 diabetes may have an option for controlling blood sugar levels without pharmacological intervention. When paired with a continuous glucose monitor (CGM) or other device as well as a source of blue light, it could create a closed loop model of managing the disease by functioning as a bioartificial pancreas.

This could be potentially life changing for individuals living with type 1 diabetes, and Diabetes Research Connection (DRC) is excited to see how the study progresses. Though not involved with this project, the DRC supports advancement of type 1 diabetes research and treatment options by providing critical funding for early career scientists pursuing novel research projects. Learn more by visiting http://diabetesresearchconnection.org.

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