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Research Study for type 1 diabetes

Proactively Identifying Type 1 Diabetes

Identifying Type 1 Diabetes Development

Type 1 diabetes develops when the body mistakenly attacks and destroys insulin-producing beta cells. As the number of cells depletes, the body is unable to adequately control blood sugar levels. Researchers have been striving to find a way to prevent this destruction from occurring or to find a way to replace these cells so that the body can once again manage its own blood sugar.

A recent study took a closer look at exactly when this transformation begins to take place and beta cells begin dying off. They found that in many participants, the decline started at least six months prior to when patients would meet clinical requirements for a type 1 diabetes diagnosis. Diagnostic thresholds are currently a “fasting glucose of ≥126 mg/mL or 2-hour glucose of ≥200 mg/dL.”

The study involved 80 patients split into three categories: younger than age 11, ages 11 to 20, and older than age 20. All participants were first- or second-degree relatives of someone with type 1 diabetes and were diagnosed themselves while undergoing oral glucose tolerance tests (OGTTs) every six months. The results showed that across all age groups, C-peptide levels started declining around 12 months before diagnosis but showed the most significant changes in function in the 6 months prior to and 12 months following diagnosis.

By tracking these changes in individuals who are considered at-risk of developing type 1 diabetes, doctors may be able to catch declining beta-cell function early on and intervene with treatment before patients reach diagnostic thresholds for the disease. This could potentially be a way to prevent or slow the onset of type 1 diabetes through proactive immunotherapy.

More research is needed to further explore these findings and expand them to a larger group of participants. However, it provides researchers with insight on when type 1 diabetes may begin to develop and some changes to focus on. Diabetes Research Connection (DRC), though not involved with this study, supports early-career scientists in pursuing novel research studies around type 1 diabetes to help advance prevention and treatment efforts as well as minimizing complications, improving quality of life, and finding a cure. Learn more about current studies and how to support these projects by visiting https://diabetesresearchconnection.org.

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Medical Technology

Helping Drive Technology Advancements

Diabetes Patients Are Helping Drive Technology Advancements

Managing type 1 diabetes is an around-the-clock job. Patients must always be aware of what their blood sugar level is, whether it is trending up or down, whether or not to administer insulin, and if they do need insulin, how much. While there have been many advancements in technology to help with monitoring and insulin administration, the development and approval process is often long and drawn out. There are a limited number of devices approved by the government for use.

Patients with type 1 diabetes have begun taking their health into their own hands and improving treatment options. There are free directions online for how patients can connect their continuous glucose monitor (CGM) and their insulin pump with their smartphone to create a closed-loop system that tracks their blood glucose and automatically administers insulin as necessary. This type of artificial pancreas is something that researchers and pharmaceutical companies have been working on for years, but to date, there is only one commercially available closed-loop system available for use in Canada.

Jonathan Garfinkel, a Ph.D. candidate in the Faculty of Arts at the University of Alberta, took his chances and used the patient-created instructions for setting up the closed-loop system two years ago, and it has been life-changing. Previously, he was having a lot of difficulty managing his blood sugar overnight, and it would drop dangerously low. With the closed-loop system, his blood sugar has become much stabler overnight, and he is not tasked with regularly doing finger pricks and figuring out insulin dosing on his own.

These advancements in technology that patients with diabetes are developing have prompted pharmaceutical companies to quicken their own pace when it comes to getting devices created and approved for commercial use. Patients are becoming increasingly more comfortable with technology and relying on smartphones, sensors, and other devices to help them stay abreast of their health.

Garfinkel himself is also working on a project to advance technology for diabetes treatment. He is in the process of developing “a more affordable glucose sensor that would sit on top of the skin, rather than being inserted subcutaneously.” It was a project he began in collaboration with Mojgan Daneshmand, an engineer and Canada Research Chair in Radio Frequency Microsystems for Communication and Sensing, who was unfortunately killed in a plane crash in January 2020. Garfinkel is continuing the work that they started together and was awarded a U of A seed grant to help.

There are so many young researchers with incredible potential who can benefit from funding that will allow them to carry out their plans and see the results. The Diabetes Research Connection provides up to $50K in funding to early-career scientists to empower them in moving forward with their novel research projects focused on type 1 diabetes. These opportunities open doors to improving the prevention, treatment, and management of type 1 diabetes, as well as improving quality of life, minimizing complications, and one day finding a cure. Learn more by visiting https://diabetesresearchconnection.org.

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Sleep Disturbances with Type 1 Diabetes

Sleep Disturbances Common with T1D

Type 1 diabetes is a disease that must be monitored around the clock. When children are awake, it is easier to tell when blood sugar may be spiking too high or dropping too low. At night, this is more challenging, and it is essential to continue testing blood sugar levels to stay within the target range and administer insulin as necessary.

Children typically rely on their parents to manage their diabetes and monitor blood sugar, whether done manually or through a continuous glucose monitor (CGM). A recent study found that children who use a CGM often sleep better at night, but it is their parents who have more disturbances in their sleep due to reacting to CGM data.

As part of a larger study, researchers evaluated the sleep quality of 46 parents of children with type 1 diabetes. The children were between the ages of 2 and 5, and some used CGMs while others did not. Parents reported on the time their children went to bed, woke up, and how long they slept. The average was 10.4 hours per night. Also, all 11 families who used CGMs wore accelerometers that tracked their sleep patterns for a minimum of four nights. The accelerometer showed an average of 9.8 hours of sleep per night for children.

According to the study, “Among the full cohort, 63% of parents reported checking their child’s blood glucose levels at least a few nights per week. Parents of children using CGMs reported a higher frequency of nighttime blood glucose monitoring compared with parents of children without a CGM.”

The percentage of parents who experienced sleep disturbances concerning blood glucose monitoring was noticeably higher than the percentage of children, at 78.3% and 17% respectively. Parents of children with CGMs reported higher levels of sleep disturbance, especially when the child’s diabetes was more difficult to manage. Additional research with a larger group of participants across a longer period of time is necessary to better understand the impact of diabetes management on sleep for parents and children.

It is important for physicians to keep in mind not just the impact a CGM or other device could have on the child’s health and quality of life, but also on the parent. Parents benefit from having proper support systems in place and information to help them cope with the challenges of managing their child’s type 1 diabetes.

Diabetes Research Connection, though not involved in this study, is committed to supporting early-career scientists focused on studying type 1 diabetes and ways to improve prevention, treatment, and quality of life, as well as one day finding a cure. One hundred percent of donations go directly to the scientists for their research. To learn more about current projects and how to help, visit https://diabetesresearchconnection.org.

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Enhancing Protection for Islets

Enhancing Protection for Islets Following Transplantation

One treatment approach for type 1 diabetes that researchers have been experimenting with and refining for more than 20 years is islet transplantation. The goal is to take insulin-producing islets from cadavers (or another source) and transplant them into individuals with type 1 diabetes so that these cells will thrive and allow the body to begin producing insulin once again.

A common challenge with this approach is protecting the cells from immune system attack or cell death from lack of oxygen. A recent study has found a way to overcome some of these obstacles by encapsulating the islets in a jelly-like substance made of collagen. This helps create a scaffolding that will not initiate an immune response yet contains the islets while allowing them to grow new blood vessels that will ultimately provide them with oxygen. Since this blood vessel regrowth can take time, the researchers also injected the scaffolding with calcium peroxide. As the calcium peroxide breaks down, it releases oxygen which is used to keep the cells alive as they settle in and begin working.

In traditional organ transplantation, the organ is surgically connected to the circulatory system meaning that the organ automatically begins receiving the oxygen and nutrients it needs for survival. Islet transplants do not work this way since the cells are not a solid organ. In addition, the cells are typically injected into the liver rather than the pancreas where they would normally occur. There is a greater risk of the pancreas having a negative reaction and destroying the islets than the liver.

The researchers tested this new bioscaffold in diabetic mice. Some mice received islets on their own, some received islets in the bioscaffold, and some received islets and calcium peroxide in the bioscaffold. The diabetic mice who received the islets and calcium peroxide demonstrated greater blood glucose control over four weeks than the other two groups. The team is now looking at the possibility of injecting the scaffolding with stem cells as well to further enhance islet survival and function.

These types of advancements in treatment are encouraging when it comes to type 1 diabetes. It is expected that the U.S. Food and Drug Administration (FDA) will approve islet transplantation as a valid treatment for T1D, rather than an experimental treatment, this year. This could increase the number of options available to patients for effectively managing the disease.

Diabetes Research Connection continues to stay abreast of changes in the field and provides critical funding for early-career scientists pursuing novel research around T1D. Learn more about current projects and how to support these efforts by visiting https://diabetesresearchconnection.org.

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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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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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