DRC & Research News

This page shares the latest news in T1D research and DRC’s community.

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Researchers Identify a New Type of Diabetes

Many people are familiar with the two most common types of diabetes – type 1 diabetes and type 2 diabetes – but other forms exist such as gestational diabetes. According to a recent study, researchers have discovered another type as well: checkpoint inhibitor-associated autoimmune diabetes or CIADM.

Immune checkpoint inhibitors are often used in the treatment of advanced cancers to block programmed cell death-1 (PD-1) receptors. However, one of the potential adverse effects of anti-PD-1 therapy is CIADM. Patients who develop this condition experience a sudden loss of insulin as well as variable glycemic control and require insulin to manage the condition.

The retrospective cohort study included 538 patients who were treated for metastatic melanoma between March 2015 and March 2018. Patients had either received only anti-PD-1 therapy, a combination of anti-PD-1 and ipilimumab, or a combination of anti-PD-1 and either ipilimumab or a placebo. Of these 538 patients, six who received only anti-PD-1 and four who received anti-PD-1 and ipilimumab developed CIADM. Demographic information showed that 90 percent were male, the median age was 62, and only one patient had a prior history of diabetes. In addition, all 10 were negative for islet antigen 2 antibodies, insulin antibody, and zinc transporter 8 antibody.

These findings open doors for larger studies and more in-depth research into this condition, which is not the same as type 1 diabetes despite requiring insulin to manage blood glucose levels. The Diabetes Research Connection (DRC) is interested to see where this study will lead and what it may mean for the future of diabetes, treatment, and understanding of the disease.

The DRC provides essential funding for early career scientists focused on studying issues related to type 1 diabetes. These studies not only aim to advance understanding and improve diagnosis, treatment, and quality of life, but also to one day find a cure.

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Could Hybrid Immune Cell Be Linked to Type 1 Diabetes?

Scientists understand a lot about the foundational cells that make up the body, but even still, they are always learning and discovering more. For instance, the body’s immune system is made of up B cells and T cells. These cells identify foreign invaders in the body – such as germs – and then attack and destroy them or create antibodies. In individuals with type 1 diabetes, these cells mistakenly destroy insulin-producing beta cells.

However, a recent study shows that scientists have discovered a hybrid cell that is a combination of both B cells and T cells. Not only does the surface of the cell have B cell and T cell receptors, it also expresses genes from both types of cells. In addition, these cells contain a unique genome sequence in B cell receptors that was only found in the cells of individuals with type 1 diabetes. Though some healthy individuals had this hybrid cell, they did not present with this specific B cell receptor sequence.

Upon further investigation, they found that this dual expresser cell binds very tightly to the HLA-DQ8 molecule, which is believed to play a major role in triggering the body’s attack on insulin-producing beta cells. Since this occurs in the early stages of type 1 diabetes development, researchers are interested in the potential for this discovery to one day support early diagnosis or prevention of the disease.

However, there are still many unanswered questions that exist. Scientists do not yet understand exactly how, why, when, or where the hybrid cells develop. While T cells originate in the thymus, B cells come from bone marrow and lymph nodes. Scientists are unclear where the overlap may occur that would combine these two distinct cells. They are also unsure why these dual expresser cells would go on to target insulin production.

This is the first time that this type of cell has been identified, so there is still a great deal of research that needs to be done. No one is exactly sure what this could mean for future understanding of type 1 diabetes and treatment options. That will come as more studies are done and more in-depth research is completed.

The Diabetes Research Connection (DRC) is excited to see where this discovery leads and the type of studies it generates. Though not involved with this study, the DRC provides critical funding to early career scientists for novel research projects related to type 1 diabetes. This is an integral part of advancing understanding and treatment of the disease.

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Exploring the Link Between Disturbed Eating and Type 1 Diabetes

 

Managing type 1 diabetes requires careful monitoring of food intake, activity, blood sugar, and insulin administration. Depending on what a person eats and when, it impacts their blood glucose levels. A recent study found that around one-third of individuals between the ages of 16 and 28 experience issues with disturbed eating behavior (DEB). Furthermore, many report restricting or omitting insulin.

The study evaluated the responses of 300 participants to the Diabetes Eating Problem Survey-Revised (DEPS-R) as well as to questions regarding diabetes distress, depressive symptoms, and self-management of the disease. They were divided into four groups based on their DEPS-R scores for baseline and then one year later. The groups were low DEB (65.7%), increasing DEB (8%), decreasing DEB (7.3%), and persistent DEB (19%).

While mean DEPS-R scores were stable from baseline to one year later, the scores were higher in females than in males – 16.53 and 15.57 in females versus 8.71 and 8.96 in males. All groups reported varying levels of insulin restriction and omission, but it did not differ significantly between males and females.

Individuals who fell into the persistent DEB group showed the highest levels of diabetes distress and depressive symptoms while those in the low DEB group showed the lowest levels.  The low DEB group also had the lowest HbA1c levels, while the persistent DEB group had the second highest. The study also found that “self-management decreased when DEB increased, and vice versa.” This could in turn lead to poorer glycemic control and increased health care costs.

The researchers found overall that DEB can occur at any age and any stage of the disease, but that evaluating adolescents and young adults for DEB and eating disorders may be beneficial in supporting better diabetes management and glycemic control.

The Diabetes Research Connection, though not involved with this study, supports early career scientists in conducting research aimed improving prevention and finding a cure for type 1 diabetes as well as minimizing complications and improving quality of life for individuals living with the disease. Through donations from individuals, corporations, and foundations, scientists can secure the critical funding they need to move forward with their research.

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Could Type 1 Diabetes Slow Brain Development in Children?

Since type 1 diabetes occurs when the pancreas produces little to no insulin, it is often diagnosed in childhood when this deficiency become more apparent. The body is unable to naturally manage blood sugar levels since the immune system mistakenly attacks and destroys insulin-producing beta cells. This means that parents must take over this responsibility until children are able to effectively manage their condition on their own.

Many parents are hesitant to overtreat and end up allowing blood sugar levels to remain slightly elevated (hyperglycemia) rather than risk having them drop too low (hypoglycemia). Neither condition is desirable as they can both lead to health complications. The goal is to create a management plan that enables blood sugar levels to remain as normal as possible.

A recent study found that hyperglycemia in children with type 1 diabetes may actually slow brain development and impact brain structure, cognitive function, and sensory processing. The study followed 138 children with type 1 diabetes between the ages of four and seven. Participants had been living with diabetes for an average of 2.4 years. These children were compared to 67 age-matched controls without type 1 diabetes.

After approximately 4.5 years, researchers found that those children with type 1 diabetes had decrements in both full-scale and verbal IQ, which was associated with hyperglycemia and an average HbA1c of 8%. The target goal for children is an HbA1c of less than 7.5%.

However, a larger study found that although full-scale, verbal IQ, and vocabulary were lower in those with T1D, there was no significant difference in processing speed, memory, or learning scores compared to the control group. The brains of children with T1D seemed to compensate for areas where there were challenges, and executive function was similar between groups.

Nelly Mauras, MD, chief of the Division of Endocrinology, Diabetes, and Metabolism at Nemours Children’s Health System and part of the Diabetes Research in Children Network (DirecNet) noted, “We are not suggesting that these youngsters aren’t performing academically. So far, these differences have not translated into functional outcomes in performance, at least not yet.”

Researchers continue to follow these groups in order to gather more information and determine the impact over a longer duration of time. They are interested in learning more about whether advanced technology can make it easier to maintain near normal glucose levels and whether HbA1c guidelines should be lower than 7.5% for children with type 1 diabetes to minimize hyperglycemia.

The Diabetes Research Connection (DRC), though not involved with this study, will continue to follow study progress to see what future comparisons hold and how this may impact treatment options and guidelines for children with type 1 diabetes. Current results may stimulate new research opportunities and increase understanding of the greater impact of T1D on health and development. The DRC provides critical funding for early career scientists to pursue novel research projects related to type 1 diabetes.

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Later Onset Type 1 Diabetes Often Misdiagnosed as Type 2

Type 1 diabetes used to be commonly known as juvenile diabetes because it was often diagnosed in childhood. In individuals with this disease, the body mistakenly attacks and destroys insulin-producing beta cells, and eventually the body is no longer able to generate enough insulin to support normal blood sugar levels. Therefore, individuals must monitor their own blood-glucose and inject themselves with insulin.

However, research has shown that around 42% of people with type 1 diabetes were diagnosed after age 30. A recent study found that some people are mistakenly diagnosed with type 2 diabetes instead due to the late onset of the disease as well as clinical and genetic characteristics. This can make it difficult to properly differentiate between the two conditions.

The study examined data from 583 participants diagnosed with diabetes after age 30 who are part of the Exeter Diabetes Alliance for Research in England (DARE). Their data was compared to 220 DARE participants with the same study criteria but who were diagnosed with type 1 diabetes before age 30.

The researchers wanted to know how many of those diagnosed after age 30 had severe endogenous insulin deficiency (meaning their body naturally produced little to no insulin on its own), whether diagnosed with type 1 or type 2 diabetes. Severe insulin deficiency is a classic sign of type 1 diabetes but C-peptide and other tests are not always conducted to check for this condition in adults age 30 or older. However, the study found that 21 percent of participants who were treated with insulin had this condition, and 38% of participants not treated with insulin at diagnosis had it.

Individuals who required rapid insulin within one year of diagnosis or who were treated with insulin within three years of diagnosis had a higher likelihood of severe endogenous insulin deficiency; 85% and 47% respectively. This means that they likely had type 1 diabetes rather than type 2, regardless of what their initial diagnosis was. Participants diagnosed after age 30 shared very similar clinical and biological characteristics with the younger cohort.

It is critical that physicians conduct necessary testing to differentiate type 1 from type 2 diabetes regardless of age of onset. There are often different protocols for treating each of these conditions, and individuals with type 1 diagnoses have greater access to necessary resources such as continuous glucose monitoring (CGM) devices, insulin-pump therapy, and targeted diabetes education.

With more awareness of the frequency of type 1 diabetes onset after age 30 and associated characteristics, hopefully medical providers will be better able to assess and accurately diagnose this condition more quickly to provide essential treatment.

The Diabetes Research Connection (DRC) strives to support early career scientists in pursuing novel research studies that focus on the prevention, diagnosis, and treatment of type 1 diabetes as well as improving quality of life for individuals living with this disease. Research is critical to one day finding a cure.

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Is it Possible to Delay the Onset of Type 1 Diabetes?

Living with type 1 diabetes (T1D) is challenging. It requires constant monitoring and adjustment of one’s blood sugar. Since T1D is commonly diagnosed in childhood, it can put additional strain on parents who must carefully manage their child’s condition. However, a recent study reveals that scientists may have found a way to delay the onset of type 1 diabetes by two years or more.

An antibody drug developed by Jeffrey Bluestone, an immunologist at the University of California, San Francisco, helps to shut down activated T cells thereby reducing the body’s immune system attacks on insulin-producing beta cells. It is the destruction of these cells that triggers T1D. Bluestone partnered with Kevan Herold, an endocrinologist at Yale University, to begin researching the potential of this drug in delaying the development of diabetes.

They first experimented with the drug on mouse models who were at high risk of developing type 1 diabetes, and it was effective in staving off the disease in many of the mice. In 2000, they shifted their work to human trials. The key was figuring out exactly when to administer the drug. If they gave it too early, there was not enough T cell activation so there was not much to protect against. Too late and there was too much T cell activity to manage. They had to find the precise time when diabetes was on the verge of developing or had been newly diagnosed.

In a trial involving 12 patients, after one year, nine of the participants had maintained or increased their body’s natural insulin production. This meant that their body was better able to manage glucose levels on its own and required less insulin to be injected.

After some setbacks and skepticism, Bluestone, Herold, and their team arranged for another trial. This time, they included participants who were at a high risk of developing type 1 diabetes within five years. They recruited 76 participants, 44 of whom received the drug (now known as teplizumab), and 32 of whom received a placebo. The drug was administered via IV infusion over 14 consecutive days. The results showed that while individuals who received the placebo were diagnosed with diabetes after an average of two years, those who received teplizumab were diagnosed after an average of four years. In addition, 72% of placebo recipients developed diabetes after five years compared to only 43% who received the experimental drug.

There is still a great deal of research and clinical testing that must be done, but this is a step forward in delaying onset of type 1 diabetes and eventually perhaps preventing development of the disease all together in high-risk individuals. Even delaying the disease by two years as the current study showed is monumental in improving quality of life. It is two fewer years of daily disease management and potential complications.

This discovery could lead to a greater understanding of diabetes prevention or delaying disease progression. It could stimulate new research and studies from scientists as they seek to advance results. The Diabetes Research Connection, though not involved with this study, provides critical funding that allows early career scientists to move forward with novel research projects. There’s no telling exactly what impact their findings could have on the future of type 1 diabetes or when the next major breakthrough will occur.

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Scientists Uncover New Insight into Autoimmune Response

Autoimmune diseases are challenging to treat because the immune system plays a critical role in keeping the body healthy. However, when this system is destroying its own cells even without the presence of an infection, it can be problematic and potentially life-threatening. Millions of people suffer from autoimmune diseases such as type 1 diabetes (T1D), lupus, and scleroderma, and treatment options—as well as their effectiveness—are limited.

However, researchers at the University of Leeds and the University of Pennsylvania have made a new discovery that could change treatment in the future. They found two proteins—BRISC and SHMT2—that together are responsible for controlling the body’s response to infection or what it deems foreign invaders.

The team is aiming to figure out a way to target these proteins and keep the immune system from attacking and destroying the body’s own cells. This could eventually generate a new class of drugs for treating autoimmune disorders, though this type of treatment is still a long way off as a wealth of research and testing still needs to be conducted regarding this process.

It is encouraging to see new developments occurring and progress being made toward better understanding autoimmune diseases such as type 1 diabetes. With advanced research, scientists can formulate improved treatment options and perhaps one day a cure.

The Diabetes Research Connection, though not involved with this study, is part of the effort toward improving prevention, treatment, and quality of life for individuals living with T1D. Through donations from individuals, corporations, and foundations, early career scientists are able to receive critical funding to support novel, peer-reviewed research projects.

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Exploring Protective Factors Against Diabetic Kidney Disease

One of the complications that can stem from living with diabetes is the risk of developing diabetic kidney disease. The kidneys play a critical role in filtering waste and excess water out of the blood and sending it out of the body. Prolonged high blood sugar and/or blood pressure can damage the kidneys and prevent them from functioning effectively. Eventually, individuals may require dialysis or a kidney transplant if damage is too extensive.

However, a recent study from the Joslin Diabetes Center found that some people have biological protective factors that may be effective in reducing risk of diabetic kidney disease. Their bodies have certain enzymes that affect glucose metabolism and protect the kidneys. Researchers studied cohorts of individuals who have been living with type 1 or type 2 diabetes for more than 50 years with minimal or no complications. They are referred to as Joslin Medalists.

One key finding was that the Medalists had increased PKM2, an enzyme in the blood that protects against diabetic kidney disease. There were also other metabolites and proteins that appeared at higher levels as well in their plasma. An interesting discovery was that the presence of an amyloid precursor protein (APP)—which is known to signal increased risk of Alzheimer’s disease—may actually work as a protective factor against diabetic kidney disease.

Scientists need to conduct additional research to further understand these potential protective factors and how they can be used to improve diagnosis and treatment of diabetic kidney disease or diabetes in general. Diabetic kidney disease can be a potentially fatal complication, so the more researchers understand about how it develops and the biological protective factors that can decrease risk, the better they can support individuals living with diabetes and their health.

Though not involved with this study, the Diabetes Research Connection (DRC) stays abreast of the latest research regarding type 1 diabetes and ways to improve diagnosis, treatment, and quality of life for individuals with the disease. Through donations from individuals, corporations, and foundations, the DRC provides critical funding for early career scientists to pursue novel research studies and further understanding of type 1 diabetes.

 

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Beta Cell Proliferation May Help Protect Against Type 1 Diabetes

In individuals with type 1 diabetes (T1D), the body’s immune system mistakenly attacks and destroys insulin-producing beta cells. For years, researchers have been looking at options for suppressing this immune system attack, as well as processes to replace beta cells or stimulate the body to produce more. A recent study by researchers at the Joslin Diabetes Center may have found a way to do both and increase protection against T1D.

Scientists found that by speeding up cell proliferation and flooding mouse models with beta cells, it stopped the immune system from destroying these cells. According to Dr. Rohit Kulkarni, HMS Professor of Medicine and Co-Section Head of Islet and Regenerative Biology at the Center, “We believe there are some alterations in the new beta cells where a number of cells being presented as autoantigens are reduced or diluted, and therefore, because of the slow presentation of the antigens, the number of autoreactive T cells are less pathogenic.” In addition, when these cells were transplanted into other mice, they appeared to have a greater resistance to stress, which could also help them to survive longer in adverse conditions.

Gaining a greater understanding of the role cell proliferation can play and determining when the ideal time to activate this process is could have a positive impact on improving protective factors against T1D. This process has not yet been tested in humans, and there would likely still be a need for some level of immune system suppression to manage lingering autoimmunity.

The Diabetes Research Connection (DRC) stays abreast of the latest developments regarding T1D and is interested to see how these findings impact future studies and treatment options for the disease. It is these types of projects that stimulate innovative studies from other researchers. The DRC provides critical funding to support early career scientists in pursuing novel, peer-reviewed research.

 

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Researchers Improve Cell Conversion to Support Diabetes Treatment

One of the methods of treating type 1 diabetes that researchers have been exploring is using patients’ own cells. They found that by converting stem cells into insulin-producing beta cells and then transplanting them into patients, it could stimulate the body to generate its own insulin. However, one of the challenges they faced is that beta cells only made up around 30 percent of the cells in the mixture following conversion.

Researchers in Douglas Melton’s lab at the Harvard Stem Cell Institute may have found a way to increase this percentage. A recent study found that by using single-cell sequencing, they were able to identify what the other 80 percent of cells in the mixture were. Then, by applying various molecular biology approaches, they could sort the cells based on expression patterns. Since beta cells contain a specific protein that other cells do not, they had another way to filter these cells out of the mix and increase the overall concentration that would be implanted into patients with type 1 diabetes.

Scientists at Semma Therapeutics also found a way to collect insulin-producing beta cells by separating all of the cells and then allowing them to cluster back together through their natural attraction to the same type of cell. This also increased the concentration of beta cells, and they could create a mixture that was around 80 percent beta cells versus the previous 30 percent.

The researchers are currently conducting more tests to determine what balance of beta cells versus other cells is most effective for regulating beta cell function and stimulating the production of insulin. However, now they have a greater understanding of the cell makeup during the conversion process and how to separate specific cell types.

This is another step toward improving treatment options for type 1 diabetes and potentially finding a cure. Advanced research is necessary for creating change. The Diabetes Research Connection provides funding for novel, peer-reviewed research studies focused on the prevention, treatment, and cure of type 1 diabetes, as well as improving quality of life for individuals living with the disease. Early career scientists can receive up to $50K to support their research.

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