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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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Targeting the Effects of Specific Drugs on Pancreatic Islets

The production of insulin and glucagon used to regulate blood sugar levels come from pancreatic islet cells. In individuals with type 1 diabetes, the immune system mistakenly attacks and destroys these cells leaving the body unable to naturally regulate blood sugar. That means that individuals must continuously monitor and manage these levels themselves.

A recent study examined the impact that specific drugs have on pancreatic islet cells and their function. Researchers were able to fine-tune single-cell transcriptomics to remove contamination from RNA molecules that could interfere with results and negatively affect reliability of the data.

Once they had created decontaminated transcriptomes, they tested three different drugs that relate to blood glucose management. They found that one drug, FOXO1, “induces dedifferentiation of both alpha and beta cells,” while the drug artemether “had been found to diminish the function of alpha cells and could induce insulin production in both in vivo and in vitro studies.” They compared these drugs in both human and mouse samples to determine if there were any differences in how the cells responded. One notable difference was that artemether did not have a significant impact on insulin expression in human cells, but in mouse cells, there was reduced insulin expression and overall beta cell identity.

Single-cell analysis of various drugs could help guide future therapeutic treatments for type 1 diabetes as researchers better understand their impact. Targeted therapies have become a greater focus of research as scientists continue to explore T1D at a cellular level.

Diabetes Research Connection (DRC) is interested to see how single-cell sequencing and the ability to decontaminate RNA sequences could affect diabetes research. The organization supports a wide array of T1D-focused studies by providing critical funding to allow early-career scientists to advance their research. To learn more and support these efforts, visit https://diabetesresearchconnection.org.

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

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

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

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

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

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

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

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

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Redifferentiating Beta Cells to Treat Type 1 Diabetes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Exploring the Impact of Type 1 Diabetes on Bone Health

The body continually goes through a cycle of bone formation and bone resorption. As bone tissue is broken down and calcium is released, new microstructures are formed to support bone growth. Issues with bone metabolism, such as low bone mineral density (BMD), can lead to osteoporosis and other conditions. Studies have shown that adults with type 1 diabetes often have lower BMD.

A recent study found that individuals with type 1 diabetes may be at risk for decreased BMD compared to individuals without the disease. In a study of 173 children and adolescents with T1D compared to 1,410 non-diabetic peers, there was a significant difference in bone turnover markers in participants with T1D. Researchers looked at three different markers based on BMD measurements and blood samples and found that individuals with T1D had fewer of all three types of markers. However, there was no significant difference between bone turnover markers and diabetes duration, or in BMD levels between the two groups.

According to Dr. Jens Otto Broby Madsen, a physician in the department of pediatrics and adolescent medicine at Herlev Hospital in Denmark, “Decreased bone turnover markers might be the first warning of a negative effect of type 1 diabetes on bone health. Bone turnover markers might be a way of screening for early changes, long before changes can be seen by DXA scans.”

This may help improve health, quality of life, and disease management in the future to decrease risk of other conditions in conjunction with T1D, or at least improve early detection. Diabetes Research Connection (DRC) strives to support novel research studies by providing critical funding to early career scientists to help them move forward with their work. It is these types of efforts that increase understanding about the disease and can improve diagnosis, prevention, treatment, and management of T1D. To learn more about current projects and how to help, visit https://diabetesresearchconnection.org.

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Advancements in Type 1 Diabetes Management Technology

One of the challenges – and frustrations – of living with type 1 diabetes (T1D) is multiple finger sticks each day to test blood sugar levels. Individuals want to ensure that they are staying on top of blood sugar in order to administer insulin or glucose as needed. Even continuous glucose monitors require a tiny needle stick in order to monitor blood sugar levels.

In a recent study, researchers share advancements using laser technology, rather than blood samples, in order to measure glucose concentration. The device they developed uses Raman spectroscopy, which shines near-infrared light on the skin to determine its chemical composition. This includes reading the signal given off by glucose located in the interstitial fluid that surrounds skin cells.

The near-infrared light only has the ability to penetrate a few millimeters into the skin, so researchers needed to find a reliable way to measure glucose from this reading. Initially, they were comparing the chemical composition of the tissue with blood samples taken simultaneously to determine glucose levels. However, there was too much unpredictability since movement of the patient or changes in the environment could alter results. In addition, it required a great deal of calibration.

The Laser Biomedical Research Center at MIT has spent more than 20 years working on developing a glucose sensor using Raman spectroscopy, and they have made a lot of advancements over the years. The latest device has evolved from indirect measurement of glucose concentrations, like those mentioned above, to direct measurement. Researchers found that by using a small fiber to collect the Raman signal after shining the near-infrared light at a 60-degree angle, they could filter out unwanted signals from other solid components in the skin. Testing the device on pigs, they were able to get an accurate glucose reading for up to an hour, and it only required about 15 minutes of calibration.

One drawback to the current technology is that the device is approximately the size of a desktop printer, meaning it is not easily portable. With a slightly smaller system, individuals could have a testing device at home or at work where they could place their finger on a sensor and Raman spectroscopy would be used to check blood sugar. Eventually, researchers would like to create a wearable monitor that would act as a continuous glucose monitor but without any needles.

After more than two decades, researchers are finally getting closer to their goal of creating a laser-based glucose sensor that can be used for everyday monitoring. It is encouraging to see advancements that seek to take some of the pain and inconvenience out of blood sugar monitoring by eliminating the need for so many needles.

Diabetes Research Connection (DRC) is excited to see how this technology continues to advance and what it may mean for the future of continuous glucose monitoring and diabetes management. Researchers around the world are focused on improving the prevention, treatment, and management of type 1 diabetes. The DRC supports these efforts by providing up to $75K in funding to early-career scientists pursuing novel research for T1D. Learn more by visiting https://diabetesresearchconnection.org.

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