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Recapping Current Research Regarding Type 1 Diabetes Development and Cardiovascular Risks

Our bodies are formed from an innumerable number of cells and molecules. Both DNA and RNA play a role in determining cells’ function and purpose. At a conference of the National Congress of the Spanish Diabetes Society, researchers revealed new studies regarding the potential role of long non-coding RNAs (lncRNAs) in the development of type 1 diabetes, as well as the risk of cardiovascular problems in individuals with the disease.

A recent study found that lncRNA, which are use in transcriptional and post-transcriptional regulation of cells and are not translated into proteins, may be involved in the destruction of insulin-producing beta cells. There may be some forms of lncRNAs that affect inflammation and cell death, which are factors in the development of type 1 diabetes.

Dr. Izortze Santín Gómez, a professor at the University of the Basque Country and a researcher at the Biocruces Bizkaia Research Institute is studying the fundamental characteristics of the lncRNAs and how they may affect pancreatic beta cells on a genetic-molecular level. Once this is better understood, researchers could begin modifying the lncRNAs to create a targeted therapy that increases survival rate and viability of the pancreatic beta cells.

Another study that was presented at the conference involved cardiovascular risk for individuals with type 1 diabetes. Joseph Ribalta, a professor at the Rovira i Vigili University of Reus, found that “more than 30% of heart attacks occur in people with apparently normal LDL cholesterol.” High cholesterol is a key risk factor for heart attacks. His findings have revealed that individuals with T1D may be at greater risk because “LDL particles are more numerous and smaller, that their HDLs work less effectively and/or that there are some lipoproteins (remnants) that the body has trouble eliminating.”

Identifying these potential risk factors and knowing how to test for or treat them could help reduce hidden cardiovascular risk in individuals with T1D. For instance, focusing on triglycerides rather than cholesterol may be beneficial for patients who meet certain criteria.

There is a lot of interesting work coming out of laboratories and universities around the world regarding type 1 diabetes. Researchers are constantly improving and refining their understanding of the disease and possible ways to prevent, treat, or cure it. Diabetes Research Connection (DRC) is committed to contributing to this wealth of knowledge by providing critical funding to early-career scientists pursuing novel research studies focused on type 1 diabetes. Learn more about current projects and how to help by visiting https://diabetesresearchconnection.org.

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Increasing Cell Protection Against Immune System Attacks

One of the challenges researchers have faced with using cell therapy to treat type 1 diabetes is that the body’s immune system may still attack and destroy transplanted cells. This process may be slightly delayed depending on the approach used, but it often still occurs. That means that patients may still need to rely on immune suppression medications in conjunction with cell therapy. However, immunosuppression can increase risk of infection or other complications.

A recent study found that targeting highly durable cells that have the ability to escape immune attacks and survive may be key in developing a more effective treatment for type 1 diabetes. Dr. Judith Agudo has identified stem cells with this “immune privilege” and is working to determine exactly what contributes to this level of protection and how to replicate it with beta cells. Dr. Agudo is an assistant professor in the department of immunology at Harvard Medical School and in the department of cancer immunology and virology at the Dana-Farber Cancer Institute.

If scientists can engineer insulin-producing beta cells that have the ability to avoid attacks from the immune system while still performing their intended functions, this could be a huge step forward in potentially treating type 1 diabetes. The beta cells would be able to stimulate insulin production without requiring the patient to take immune suppression medications, meaning their immune system could continue to function as normal and fend off infection.

Once Dr. Agudo is able to develop these durable beta cells, they will be tested in animal models, followed by humans a few years later. It is important to conduct thorough testing to ensure this method is both safe and effective. If it is, the goal would be to eventually make it available to anyone who requires the use of insulin.

Diabetes Research Connection (DRC) is excited to see how this study evolves and what it could mean for the future of diabetes treatment. While not involved in this study, the DRC plays an integral role in providing critical funding for early career scientists focused on research for type 1 diabetes. Scientists continue to advance understanding of the disease and potential approaches to improve diagnosis, treatment, management, and quality of life for individuals living with type 1 diabetes. Learn more about current DRC projects and how to support these efforts by visiting 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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Improved Protection for Transplanted Stem Cell-Derived Islets

Insulin-producing beta cells are essential for effective blood sugar control. However, in individuals with type 1 diabetes, these cells are mistakenly destroyed by the immune system. That means exogenous insulin must be used instead to manage blood sugar. For years, scientists have been researching ways to replace or reproduce these islet cells. Two of the most common challenges faced, however, have been the need for long-term immunosuppression to protect transplanted cells from rejection, and limited availability of donor cells.

A recent study found that an improved source of encapsulation may protect islet cells from an immune response without decreasing their ability to secrete insulin. By using a conformal coating that is only a few tens of micrometers thick (as opposed to hundreds of micrometers thick), not only could insulin flow more freely through the encapsulation, so could oxygen, nutrients, and glucose as well. Yet larger immune cells were still unable to penetrate the barrier. In addition, the thinner coating allowed for more cells to be contained in a smaller space, and the capsule could be implanted in a wider range of locations so long as there was strong vascular function.

The encapsulated cells were implanted in NOD-scid mice and compared with non-coated stem cells as well as human islets. There were no statistically significant differences in performance of the cells and their ability to regulate glucose levels. The mice all showed a reversal in diabetes with the transplanted cells and returned to hyperglycemia once the cells were explanted.

The use of a microencapsulation method allows for more variability in placement of transplanted cells and helps protects against hypoxia-induced islet death and cell rejection. Furthermore, the thinner coating enabled islets to obtain better oxygenation because they are closer to blood vessels. It also allowed insulin to be secreted more quickly because it flowed more freely through the barrier.

One drawback that researchers noted was that encapsulated islets are unable to shed dead cells because they are contained within the capsule and have a lower absolute quantity of insulin secretion when compared to non-coated stem cell-derived islets.

Through this study, the researchers concluded that, “CC (conformal-coated) mouse islets can reverse diabetes long-term in a fully MHC-mismatched model.” While additional research is necessary to explore the effectiveness of this process in humans, it is a step in the right direction toward one day potentially curing type 1 diabetes.

Though not involved with this study, Diabetes Research Connection (DRC) stays abreast of the latest advancements in the field and provides critical funding to early career scientists pursuing novel research studies for type 1 diabetes. It is through these types of projects that researchers are able to improve quality of life for individuals living with the disease and move closer to finding a cure. To learn more about current DRC-funded projects or support these efforts, visit https://diabetesresearchconnection.org.

 

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Exploring Why the Immune System May Attack Insulin-Producing Beta Cells

Insulin-producing beta cells are essential for effective blood sugar control. However, in individuals with type 1 diabetes, these cells are mistakenly destroyed by the immune system. That means exogenous insulin must be used instead to manage blood sugar. For years, scientists have been researching ways to replace or reproduce these islet cells. Two of the most common challenges faced, however, have been the need for long-term immunosuppression to protect transplanted cells from rejection, and limited availability of donor cells.

A recent study found that an improved source of encapsulation may protect islet cells from an immune response without decreasing their ability to secrete insulin. By using a conformal coating that is only a few tens of micrometers thick (as opposed to hundreds of micrometers thick), not only could insulin flow more freely through the encapsulation, so could oxygen, nutrients, and glucose as well. Yet larger immune cells were still unable to penetrate the barrier. In addition, the thinner coating allowed for more cells to be contained in a smaller space, and the capsule could be implanted in a wider range of locations so long as there was strong vascular function.

The encapsulated cells were implanted in NOD-scid mice and compared with non-coated stem cells as well as human islets. There were no statistically significant differences in performance of the cells and their ability to regulate glucose levels. The mice all showed a reversal in diabetes with the transplanted cells and returned to hyperglycemia once the cells were explanted.

The use of a microencapsulation method allows for more variability in placement of transplanted cells and helps protects against hypoxia-induced islet death and cell rejection. Furthermore, the thinner coating enabled islets to obtain better oxygenation because they are closer to blood vessels. It also allowed insulin to be secreted more quickly because it flowed more freely through the barrier.

One drawback that researchers noted was that encapsulated islets are unable to shed dead cells because they are contained within the capsule and have a lower absolute quantity of insulin secretion when compared to non-coated stem cell-derived islets.

Through this study, the researchers concluded that, “CC (conformal-coated) mouse islets can reverse diabetes long-term in a fully MHC-mismatched model.” While additional research is necessary to explore the effectiveness of this process in humans, it is a step in the right direction toward one day potentially curing type 1 diabetes.

Though not involved with this study, Diabetes Research Connection (DRC) stays abreast of the latest advancements in the field and provides critical funding to early career scientists pursuing novel research studies for type 1 diabetes. It is through these types of projects that researchers are able to improve quality of life for individuals living with the disease and move closer to finding a cure. To learn more about current DRC-funded projects or support these efforts, visit https://diabetesresearchconnection.org.

 

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Understanding the Impact of GABA on Insulin Secretion and Regulation

In order to manage blood glucose levels, pancreatic beta cells release insulin in pulses. These bursts of insulin help the body to regulate and stabilize blood sugar. In individuals with type 1 diabetes, however, the pancreatic beta cells that normally secrete insulin are mistakenly destroyed by the body. This leaves the body unable to effectively regulate blood sugar on its own. Understanding the interaction between insulin-producing beta cells and other processes in the body may help researchers improve treatment and prevention options when it comes to diabetes.

A recent study examined the different roles gamma amino-butyric acid (GABA) plays in cell activity. In the brain, GABA is released from nerve cell vesicles each time a nerve impulse occurs. The GABA prepares cells for subsequent impulses by working as a calming agent. Researchers previously believed that this process worked in much the same way in the pancreas.

However, in the pancreas, GABA is evenly distributed throughout the beta cells rather than contained within small vesicles, and it is transported via the volume regulatory anion channel. This is the same channel that helps stabilize pressure inside and outside of cells so that they maintain their shape. Furthermore, research showed that GABA is released in a similar pattern and frequency as pulsatile in vivo insulin secretion. Just like in the brain, GABA plays an integral role in preparing and calming cells to make them more receptive to subsequent insulin pulses.

Scientists are interested in learning more about how GABA signaling can support the regulation of insulin secretion and potentially protect cells from autoimmune activity. This opens new doors for biomedical research that has the ability to impact diabetes care.

It is encouraging to see different types of researchers all coming together and learning from and building upon one another’s work in order to advance understanding, prevention, and treatment of various diseases, including diabetes.

Diabetes Research Connection stays abreast of the latest discoveries in the field and supports early career scientists in contributing to this body of work by providing critical funding for their projects. It is essential that scientists have the resources to pursue novel research in order to develop improved prevention, treatment, and management options for type 1 diabetes. Learn more and support current projects by visiting https://diabetesresearchconnection.org.

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Could Higher-Dose and Lower-Dose Insulin Glargine be Equally Effective in Managing Type 1 Diabetes?

In an effort to maintain greater blood-glucose stability throughout the day and minimize highs and lows, some individuals with type 1 diabetes use insulin glargine, which is a once-a-day, long-acting insulin. It is an analogue, or laboratory-created, insulin which has been modified to act more uniformly in managing glucose levels.

Insulin glargine comes in varying strengths, and a recent study found that there were no significant differences in safety or effectiveness between insulin glargine 100 U/mL and insulin glargine 300 U/mL when administered in children and adolescents. Data from 463 EDITION JUNIOR study participants between the ages of 6 and 17 were compared over 26 weeks. Of those participants, 233 were randomly assigned to insulin glargine 300 U/mL, and 228 were randomly assigned to insulin glargine 100 U/mL. Both groups continued to follow their normal routine for mealtime insulin but injected insulin glargine once per day.

Results showed that all participants experienced a reduction in HbA1c levels over the 26 weeks. However, there were fewer instances of severe hypoglycemia among participants using the insulin glargine 300 U/mL, though overall, results were comparable between groups. Both insulins were effective in achieving target study endpoints and did not demonstrate any unexpected safety concerns.

In comparing insulin glargine 100 U/mL and insulin glargine 300 U/mL, researchers may be able to use insulin glargine 300 U/mL as yet another treatment option for children and adolescents with type 1 diabetes. It is currently under review by the FDA, and researchers are evaluating data from a six-month safety follow-up.

It is encouraging to see that more options are being explored to meet the needs of individuals living with type 1 diabetes in order to maintain target glucose levels with fewer fluctuations. Diabetes Research Connection (DRC) will continue to follow these types of studies to see how they impact the future of diabetes management and accessibility to care.

DRC provides critical funding for early career scientists pursuing novel, peer-reviewed research studies for type 1 diabetes. Projects aim to improve prevention and treatment of the disease, as well as enhance quality of life and eventually find a cure. To learn more about current studies and support these efforts, visit http://diabetesresearchconnection.org.

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Unraveling the Process of Fetal Pancreas Development

Cell replacement therapy has been at the forefront of type 1 diabetes research for many years. Researchers have explored different ways to reintroduce insulin-producing beta cells into the pancreas or stimulate the body to begin producing these cells once again. A major challenge is often rejection of the cells by the body, or limited sustainability due to poor vascularization or an autoimmune response.

However, a recent study looks at the function of human multipotent progenitor cells (hMPCs) during development of the pancreas in human fetuses. Scientists were able to safely recover live cells from fetal tissue during the second trimester of development. They found that hMPCs located within the tip of the epithelium contained both SOX9 ad PTF1A transcription factors. However, according to their research, “tip cells did not express insulin, glucagon, or amylase,” which demonstrated their lack of lineage-specific markers. That means that they were uncommitted cells and could potentially differentiate into any of the three major types of pancreatic cells: ductal, endocrine, or acinar.

The proportion of SOX9+/PTF1A+ cells greatly decreased during the second trimester, however.  They accounted for more than 60% of cells up to 13.5 weeks of gestation, but after that, there was a significant decrease over the following weeks to less than 20%. During the second trimester, hMPCs also begin the process of branching morphogenesis and divide between tip and truck cells.  Truck cells become ductal and endocrine cells, but tip cells become acinar cells.

As researchers gain a deeper understanding of how the pancreas develops and how cell expression and differentiation takes place, they may be able to enhance cell replacement therapy options. According to the study, “This first ‘snapshot’ of the transcriptional network of human pancreatic progenitors opens new avenue in understanding human pancreas development, pancreatic specification and supports our ultimate goal of understanding possible mechanisms for pancreas regeneration.”

Diabetes Research Connection (DRC) is interested to see how this research may influence future treatment options for individuals with type 1 diabetes.  By better understanding the pancreas at a cellular level, it could stimulate more advanced therapies. The DRC provides critical funding for novel, peer-reviewed research studies focused on the diagnosis, treatment, and eventual cure for type 1 diabetes. Early career scientists have the opportunity to move forward with their research and contribute to the growing understanding of the disease and treatment options. Learn more and support these efforts by visiting http://diabetesresearchconnection.org.

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Is Cannabis Use Safe for Individuals with Type 1 Diabetes?

Cannabis use has been a hot topic in recent years with more states legalizing recreational use in addition to medicinal use. Just like any drug, cannabis has its risks and benefits which can vary from person to person depending on their individual situation.

A recent study looked at how cannabis use may impact individuals with type 1 diabetes in regard to diabetic ketoacidosis (DKA). DKA occurs when the body does not make enough insulin and ketones build up in the bloodstream due to the breakdown of fats instead of sugars.

The study found that moderate cannabis users with type 1 diabetes are twice as likely to develop DKA than non-users. Researchers used data from 932 adults who participate in the T1D Exchange clinic registry (T1DX).

It is important for individuals with T1D to understand the risks associated with using cannabis and how it can potentially affect their overall health and well-being, especially in regard to diabetes management. DKA can develop very quickly and can be potentially fatal if left untreated.

Though not involved in this study, the Diabetes Research Connection (DRC) supports early career scientists in pursuing novel research studies to advance understanding of T1D as well as improve diagnosis, treatment, and prevention strategies. Learn more about current projects and how to support these efforts by visiting http://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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Evaluating the Effect of Specific T Cells on Type 1 Diabetes Risk and Treatment

As researchers delve more deeply into trying to understand the origins of type 1 diabetes (T1D), they become increasingly aware that there is not a single disease pathogenesis, but rather multiple paths that vary from person to person. While they know that T1D results from the immune system attacking and destroying insulin-producing beta cells in the pancreas, there may be several different factors that contribute to this risk.

A recent study examined a variety of T cells, T cell receptors, antigens, and autoantibodies that may play a role in the development of T1D. One common factor they found was that individuals with an elevated level of islet autoantibodies in the peripheral blood are at increased risk of developing T1D within their lifetime. Researchers also know that in addition to risk genes, human leukocyte antigen (HLA) genes and the autoantibody glutamic acid decarboxylase (GAD) could vary from person to person and impact the effectiveness of targeted therapies. Children who possess two or more islet autoantibodies have around an “85% chance of developing T1D within 15 years and nearly a 100% lifetime risk for disease development.”

However, the mere presence of islet autoantibodies does not demonstrate disease state, because it could be years before clinical T1D presentation. In its early stage (stage 1), while the autoantibodies are present, beta cell function remains normal. As risk for T1D advances (stage 2), metabolic abnormalities develop. Finally, with T1D onset (stage 3), there is both a presence of autoantibodies and loss of beta cell function in regard to blood glucose. The staging paradigm was derived from data from the United States’ Diabetes AutoImmunity Study in the Young (DAISY), Finland’s Type 1 Diabetes Prediction and Prevention Study (DIPP), and Germany’s BABYDIAB studies.

Given the similarities of mouse models and human models when it comes to diabetes, mouse models are often used to study disease risk, evaluate pathogenesis, and assess potential treatment options. Researchers have found that specific antigens and T cells affect pancreatic islets differently. Understanding these antigen subsets could be critical in determining effective clinical therapeutics for prevention and treatment.

Thanks to the Network for Pancreatic Organ Donors (nPOD), more than 150 cases have been collected from organ donors with T1D since 2007, as well as more than 150 from non-diabetic donors and dozens of donors with autoantibodies but no clinical diabetes. These tissue donations have provided researchers with islets, cells, and data from multiple facets of the ody that contribute to T1D risk.

Understanding tissue specific T cells, antigens, and autoantibodies may help identify biomarkers of disease activity which could improve targeted therapeutic interventions. Eventually, this may help reduce risk of T1D by creating early intervention strategies.

While not involved with this study, Diabetes Research Connection (DRC) is focused on advancing understanding of T1D and improving prevention, diagnosis, and treatment options as well as progress toward a cure. Early career scientists receive critical funding to pursue novel, peer-reviewed research projects regarding multiple aspects of T1D. Learn more by visiting http://diabetesresearchconnection.org.

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