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Pancreatic beta cell regeneration

Examining Pancreatic Beta Cell Regeneration Processes

Researchers often use cell cultures and tissue slices to study the function and processes of various cells. One of the challenges of this approach, however, is the viability of these samples. For instance, pancreatic tissue slices typically show significant cell death after less than 24 hours due to poor oxygenation. This means that only short-term studies are possible, using samples while they are most viable and representative of the integrity of the native organ.

But, researchers are looking to change that. In a recent study, scientists altered how human pancreatic slices (HPSs) are cultured and managed to preserve function for 10 days or more. This is significant when it comes to being able to conduct longer-term longitudinal studies. Studies were also conducted on tissue samples from non-transgenic mice.

Traditionally, HPSs are preserved in standard transwell dishes. In this model, tissue is placed on top of a liquid-permeable membrane and surrounded with an air-liquid medium. However, oxygenation begins to decrease within several hours, and signs of anoxia appear. A new approach uses perfluorocarbon (PFC)-based dishes. This model places tissue atop a liquid-impermeable membrane providing direct contact with oxygen. An air-liquid medium also surrounds the slice. A variety of testing shows that PFC-based cultures have improved oxygenation and lower levels of anoxia.

In turn, this allowed scientists to more effectively study pancreatic beta-cell regeneration processes. HPSs retain “near-intact cytoarchitecture” of the organ in its native state in the body. Combined with the longer-term viability of the samples in the PFC-based setting, researchers were able to focus in on how and where beta cells were regenerating. They used HPSs from non-diabetic individuals as well as those with type 2 diabetes to enhance their understanding of how to stimulate this regeneration and improve insulin production.

When samples were left to rest for 24 hours to reduce the impact of stress from slicing and then treated with Bone morphogenetic protein 7 (BMP-7) proteins, scientists found that they showed higher levels of beta-cell regeneration than controls that were not treated with BMP-7. Much of this cell development occurred in regions corresponding to pancreatic ducts. Some new cells emerged from existing beta cells, while others transitioned from alpha to beta cells.

Improved oxygenation methods are changing how scientists are able to interact with HPSs and the types of testing they are able to conduct. According to the study, “Our goal in refining the conditions for the long-term survival of HPS was to allow for the real-time detection and quantification of endocrine cell regeneration.” While more in-depth and extensive studies are needed, these findings may lead the way toward improved understanding of the pathology of pancreatic beta-cell regeneration and new treatment options for individuals with type 1 diabetes.

Diabetes Research Connection (DRC) is committed to supporting these types of advancements and efforts by providing critical funding to early-career scientists pursuing novel, peer-reviewed research related to type 1 diabetes. With adequate funding, scientists are able to bring their ideas to life and contribute to not only greater understanding of the disease, but improved methods and therapies for diagnosing, treating, managing, and eventually curing type 1 diabetes. Learn more about current projects and support these efforts by visiting https://diabetesresearchconnection.org.

 

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Could Insulin Management be Controlled with an App?

Determining the appropriate amount of insulin to administer in response to drops in blood sugar can be challenging, but it is something that individuals with type 1 diabetes must do daily in order to manage their health. If left untreated, low blood sugar (or hypoglycemia) can be potentially fatal.

A team of researchers and physicians at Oregon Health & Science University (OHSU) are looking to improve diabetes management through a new app called DailyDose. While there are similar types of apps that exist, what sets DailyDose apart is that has demonstrated statistically relevant outcomes through multiple clinical studies. The AI algorithm for the app was originally developed entirely through a mathematical simulator, but when real-world data was used, the recommendations generated by the app aligned with recommendations provided by physicians, or were still considered safe, more than 99% of the time. In addition, improved glucose control was achieved. This was determined after 100 weeks of testing conducted in four-week trials.

Each trial involved 16 patients with type 1 diabetes and combined information from a continuous glucose monitor or wireless insulin pen with the app. Nearly 68% of the time, the recommendations generated agreed with those of physicians.

These findings are important because they show that the app may be effective in supporting individuals with type 1 diabetes in reducing risk of hypoglycemia by better managing insulin administration and blood glucose levels between appointments with their endocrinologist. Larger clinical trials are needed over longer periods of time to further determine the accuracy and effectiveness of the app in relation to other treatment strategies.

Technology is becoming increasingly more popular and advanced in terms of managing type 1 diabetes. There are numerous devices and apps already available and more in the works. This gives individuals with type 1 diabetes a wider variety of options in order to determine what works best for their needs and lifestyle.

Though not involved with this study, the Diabetes Research Connection (DRC) strives to continue growing understanding of type 1 diabetes and improving prevention and treatment methods as well as one day finding a cure. Early-career scientists can receive critical funding through the DRC to pursue novel research studies around T1D. Learn more about current projects and how to support these efforts at http://diabetesresearchconnection.org.

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Could Advancements in Gene Editing Reverse Type 1 Diabetes?

Gene therapy is not a new approach when it comes to treating type 1 diabetes. Scientists have been experimenting with many different options in order to stimulate the body to once again produce its own insulin and reduce or eliminate the need for insulin injections. However, some of the problems that scientists often encounter when introducing new cells into the body are that patients typically require immunosuppressant drugs which can lead to a variety of complications, the body rejects the cells over time, or the cells stop working. Finding a long-term, effective solution has been challenging.

Scientists are making strides in their efforts, though. A recent study examined the potential of using the gene-editing tool CRISPR to correct genetic mutations and create induced pluripotent stem cells that can be transformed into pancreatic beta cells. In mouse models, after the new cells were injected, mice achieved normoglycemia within a week and maintained this status for at least six months.

This approach has not yet been tested in humans, however, because it comes with its own set of challenges. First, the study was done using cells from patients with Wolfram syndrome, a condition that causes diabetes and deafness. This condition can be pinpointed to a single genetic mutation, whereas type 1 diabetes cannot. Type 1 diabetes has been tied to multiple gene mutations, as well as environmental factors. Gene-editing would have to be personalized for each individual, which could take a lot of time.

In addition, it could take billions of cells to effectively reverse diabetes in a patient, and generating this massive number of cells could take months, so it could end up being a long process to treat even one person. Plus, scientists are not entirely sure where the best place to transplant these cells is yet. They must find the spot where they will be most beneficial and able to carry out their intended purpose.

Another study using CRISPR technology is being conducted by a different group of researchers and is focused on using stem cells from the human cell line rather than from individual patients. This would make it easier to produce mass quantities of cells in a shorter period of time. It also would not require scientists to correct specific genetic mutations. CRISPR would be used to edit cells to prevent them from being attacked and destroyed by the body’s immune system.

A challenge with these approaches is that there are a lot of questions and regulations when it comes to gene-editing and using CRISPR on human subjects. Clinical trials are still in very early stages. Studies involving induced pluripotent stem cells are also relatively new in the United States. There is still a lot of work, research, and testing that needs to be done before gene-editing therapy could potentially be used on humans.

Diabetes Research Connection (DRC) will continue to follow these advancements and what they could mean for future diabetes treatment. DRC supports early-career scientists in contributing valuable discoveries and information of their own to the field by providing critical research funding. All projects funded by the DRC are focused on the prevention, treatment, and cure of type 1 diabetes, as well as minimizing complications and improving the quality of life for individuals living with the disease. Learn more and support these efforts by visiting https://diabetesresearchconnection.org.

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Exploring the Impact of Type 1 Diabetes on COVID-19

For the past several months, the world has been struggling to contain the spread of COVID-19 and effectively treat patients diagnosed with this disease. It is a new strain of coronavirus that researchers continue to learn more about every day. One thing that is known about the virus is that individuals with underlying health conditions are at increased risk of developing severe illness and complications.

One such underlying health condition that researchers are paying closer attention to is type 1 diabetes (T1D). Preliminary research from small studies appear to show that individuals with T1D are at increased risk of poorer health outcomes than those with type 2 diabetes (T2D) or no history of diabetes. A recent study of 64 individuals with T1D and confirmed or suspected COVID-19 in the United States found that “more than 50% of all cases reported hyperglycemia, and nearly one-third of patients experienced DKA.” Both hyperglycemia and diabetic ketoacidosis (DKA) can be life-threatening conditions if not properly treated in time.

Furthermore, research released from the United Kingdom’s National Health Service (NHS) revealed that hospitalized individuals with T1D are significantly more likely to die from COVID-19 than those with T2D. Scientists believe that hyperglycemia may enhance the immune system’s overresponse thereby exacerbating the impact of severe infections.

Being hospitalized can make it more difficult for individuals with T1D to maintain glycemic control because their body is already trying to fight off infection, and they may not have the mental clarity or ability to effectively monitor their own blood sugar. Diabetes Research Connection (DRC) sponsored a study by Addie Fortmann, Ph.D., regarding the use of continuous glucose monitors (CGMs) in hospital settings, which found that these devices were pivotal to glycemic control. As a result, Scripps deployed this technology across all of their hospitals to better support diabetes management.

But not every hospital in the United States allows patients to use their CGM while admitted, and not all staff is adequately trained in diabetes care. This can complicate things for patients struggling with T1D as well as COVID-19 and contribute to poorer health outcomes. Not only are patients fighting against the effects of COVID-19 including fever, shortness of breath, dry cough, nausea, body aches, and fatigue, if their blood sugar should go too high or too low, this can add to more symptoms and complications. In both patients with confirmed and suspected COVID-19 as well as T1D, DKA was the most prevalent adverse outcome.

It is essential that attention is given to managing underlying conditions such as diabetes in order to provide more effective treatment tailored to patient needs. Since 2012, the DRC has been providing critical funding for early-career scientists pursuing novel, peer-reviewed research related to type 1 diabetes. This work is essential to advancing understanding of the disease, improving prevention strategies and treatment options, minimizing complications, enhancing quality of life, and working toward a cure. Learn more about current projects and how to support these efforts by visiting https://diabetesresearchconnection.org.

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Taking Steps to Prevent Diabetic Ketoacidosis in Pediatric Patients with Type 1 Diabetes

There are many complications that can occur with type 1 diabetes, but one of the most serious is diabetic ketoacidosis (DKA). When the body does not produce (or have) enough insulin to help convert sugar to energy, it begins breaking down fat and using that as fuel instead. However, this releases acid known as ketones into the bloodstream, in turn leading to DKA when levels become too high.

A recent study found that DKA among newly diagnosed pediatric patients with type 1 diabetes is alarmingly high among patients around the world. During an 11-year study spanning from 2006 to 2016, researchers found that out of 59,000 children who had been diagnosed with T1D, 29.9% presented with DKA at diagnosis. The study examined data from children in Austria, the Czech Republic, Germany, Italy, Luxembourg, Norway, Slovenia, Sweden, Wales, Australia, New Zealand, and the United States.

Of these countries, prevalence rates in Luxembourg and Italy were found to be the highest at 43.8% and 41.2%, respectively, while Sweden and Denmark had the lowest rates at 19.5% and 20.8%, respectively. DKA at diabetes diagnosed increased over the 11-year study in the United States, Australia, and Germany. Overall, DKA tended to impact a higher proportion of females than males, except in Wales.

In order to help reduce risk of DKA at diagnosis, the researchers encourage improved screenings beginning with young children. For example, Bavaria, Germany tests for islet autoantibodies as part of a public health screening for children between the ages of 2 and 5. Studies showed that their prevalence of DKA at diagnosis came in at less than 5%. Increased screenings and education may be beneficial in raising awareness and catching potential problems early on before DKA develops.

Though not involved with this study, the Diabetes Research Connection (DRC) is committed to improving understanding, prevention, and treatment of type 1 diabetes by providing critical funding for novel, peer-reviewed research studies by early-career scientists. Find out how to support these efforts and learn more about current projects by visiting https://diabetesresearchconnection.org.

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Managing Blood Sugar During Exercise with Long-Acting Insulin

Engaging in regular physical activity is good for overall health. It helps with weight management, blood pressure, cardiovascular health, blood sugar, and more. Individuals with type 1 diabetes may find exercise helpful in improving insulin sensitivity and reducing the amount of insulin needed following activity. However, this can also be a challenge because they must carefully monitor their blood-glucose levels to ensure that they do not become too low or too high.

A recent study found that combining long-acting insulin (degludec) with the use of an insulin pump can be beneficial for managing glucose levels during and after exercise. Some individuals with T1D prefer to remove their insulin pump during exercise, and by administering degludec before starting exercise, they were able to remain in target range (70-180 mg/dL) for longer periods of time than when just using the insulin pump alone.

The study involved 24 physically active adults who participated in two phases of workouts that included five weeks of high- and moderate-intensity sessions. During one phase, they only used their insulin pump to control their basal insulin needs, and for the second, they used the insulin pump and the degludec. When using the insulin pump alone, they spent an average of 143 minutes (40% of the time) in target range, but when using the degludec, this time in range increased to 230 minutes (64% of the time).

The researchers found that “this was down to a significant 87-minute reduction in time spent in hyperglycemia, with no difference seen for hypoglycemia” as well. In addition, when using the hybrid insulin approach, blood sugar rose just 14.5 mg/dL after 30 minutes following exercise, compared to an 82.9 mg/dL increase using the insulin pump alone.

More than two-thirds of participants found the hybrid insulin regimen useful, and nearly half said they were somewhat or very likely to continue using this approach while exercising in the future. The researchers are looking at moving forward with a larger study to see if these results continue to be significant when more people are involved.

This study shows that there may be more than one effective option for improving glucose control during exercise for individuals with type 1 diabetes. They do not have to rely on the insulin pump alone, and some may find administering degludec beneficial when exercising without their insulin pump.

Diabetes Research Connection (DRC) is interested to see how this study plays out in the future and if more people can benefit from the hybrid insulin regimen while exercising. It is encouraging to see more options become available to help individuals better control their diabetes while improving their health and quality of life. DRC supports early-career scientists in pursuing novel research on type 1 diabetes by providing access to funding. The goal is to one day find a cure while also improving prevention, treatment, and management of the disease. Learn more by visiting http://diabetesresearchconnection.org.

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Could Benefits of Early Screening for Type 1 Diabetes Outweigh Costs?

Advances in science have improved the ability to identify warning signs for type 1 diabetes (T1D) early on. For instance, scientists can detect the destruction of insulin-producing beta cells before noticeable signs of diabetes emerge or conditions such as diabetic ketoacidosis (DKA) occur. They have also determined other key changes and factors that may put an individual at increased risk.

A recent study found that conducting health screenings on children can increase awareness regarding their risk of developing T1D, help prevent DKA occurrences, and encourage individuals to take better care of their health to reduce complications and impact of the disease.

Researchers at the Barbara Davis Center for Diabetes at the University of Colorado School of Medicine created the Autoimmunity Screening for Kids (ASK) study to determine if this type of health screening is beneficial. While it can be costly to conduct widespread screenings for children between the ages of 1 and 17, they found that there are a host of benefits such as those mentioned above. In addition, the long-term cost savings can quickly make up for screening expenses because when individuals know their risk and learn how to better manage their T1D, it can reduce complications and associated healthcare costs.

Now they are looking at how to effectively implement screenings, what the practice would look like, what the age schedule for screenings should be, and who would benefit most. Early detection can play an integral role in managing T1D and improving quality (and quantity) of life.

Diabetes research occurs at all stages of the disease, from the time patients are pre-symptomatic to those with the most serious complications. It covers everything from screenings to closed-loop systems for treatment to understanding the cellular and molecular impact of the disease. Diabetes Research Connection is committed to supporting a wide range of T1D research by providing critical funding to early-career scientists. Learn more about current projects and how to help by visiting 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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