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Exploring the Use of Targeted Proteins in Managing Type 1 Diabetes

Currently, the most effective treatment for type 1 diabetes is the administration of insulin, but this is not a perfect solution. Since the body is unable to produce enough – or in some cases any – insulin on its own, individuals are tasked with carefully determining when and how much they need to keep blood sugar levels in check. This in itself can be challenging, and too much or too little insulin can lead to potentially life-threatening hyper- or hypoglycemia.

In addition to controlling blood sugar, insulin also helps regulate ketones within the blood. Ketones are created when lipids are broken down by the liver because the body is lacking glucose. Increased ketone levels can lead to diabetic ketoacidosis. Trouble controlling fat in the blood can put individuals at a greater risk for cardiovascular problems.

However, a recent study by researchers at the University of Geneva in Switzerland reveals that combining insulin with high doses of the protein S100A9 may improve regulation of glucose as well as lipids. Though it has only been tested in insulin-deficient diabetic mice thus far, the researchers are in the process of gaining approval for phase I human clinical trials. Other studies have already shown that there is a reduced risk of diabetes in individuals with higher levels of S100A9, so they are hopeful that this protein can play an integral role in diabetes management as well.

Another interesting discovery that the researchers made was that S100A9 was only effective when cells with TLR4 receptors were present as well. At this point, they are unsure exactly what the relationship is and why TLR4 is necessary for the process to work. However, their study leads the way toward reducing the amount of insulin necessary to effectively control blood glucose and ketone levels by combining it with the S100A9 protein.

Though not involved in this study, Diabetes Research Connection (DRC) is excited to see how it progresses once human clinical trials begin as it has the potential to impact treatment for millions of people living with type 1 diabetes. The DRC supports the advancement of research and treatment through providing critical funding to early career scientists pursuing novel research studies for the disease. Find out how to support these efforts and learn more about current projects by visiting https://diabetesresearchconnection.org.

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Islet Transplantation May Have Long-Term Benefits for Type 1 Diabetes.

Islet transplantation is not a new concept, but it is one that scientists are continually trying to refine and improve. A major challenge with this procedure is rejection or destruction of the transplanted cells. However, researchers followed up with a group of 28 patients who had undergone islet transplantation and found that 10 years later, there were still lasting benefits.

A recent study looked on how patients fared a decade after receiving transplants. Fourteen of the patients received only an islet transplant, while the other 14 had a kidney graft in addition to the islet transplant. Regardless of procedure, researchers found that “28% remained completely independent of exogenous insulin” after 10 years, a slight decrease from the 39% who were independent of insulin use after five years. However, even those participants who did return to needing insulin had improved glycemic control and a lower exogenous insulin requirement than prior to transplantation. In addition, they had fewer severe hypoglycemic events.

A major factor in the effectiveness of the transplant was graft function. Those individuals who had optimal graft function maintained insulin independence longer than those who had poorer graft function. Immunosuppression was used to help support graft survival, but there were some serious adverse events as a result. In the 28 participants, there were eight instances of infections or skin carcinomas and 11 diabetes-related events that were cardiovascular.

Five participants experienced symptomatic cardiovascular events and six experienced asymptomatic myocardial ischemia. One person died of a stroke. However, researchers report that “mortality rate in patients similar to those in the current study but who did not undergo islet transplantation is three to four times higher with causes of death largely being severe hypoglycemia or ischemic heart disease.”

It is encouraging to see that a decade after islet transplantation, participants are still experiencing positive outcomes in regarding to diabetes management, with some maintaining insulin independence. As researchers continue to learn more and are able to refine and improve islet transplantation, more patients may benefit long-term from this treatment option and potentially achieve insulin independence.

Diabetes Research Connection (DRC) stays abreast of the latest findings in the field and provides critical funding for early career scientists to pursue research related to type 1 diabetes. It is through this work that improved treatments become available and scientists enhance their understanding of the disease. Learn more about these efforts and how to support existing projects by visiting https://diabetesresearchconnection.org.

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Could Closed-Loop Systems Improve Blood Glucose Management?

One of the latest technologies being tested for managing type 1 diabetes is a closed-loop system. This system uses a continuous glucose monitor (CGM) to measure blood glucose levels. When blood sugar begins to rise outside of the target range, it sends information to an insulin pump to automatically administer insulin. When blood sugar begins to fall, insulin is not administered. It is a closed loop because the patient is not deciding when to inject insulin or how much, but rather the system does so automatically.

A recent study involving 168 individuals with type 1 diabetes between the ages of 14 and 71 were part of a six-month trial using a closed-loop system. One hundred and twelve people were randomly assigned to the closed-loop group while the remaining 56 people used a sensor-augmented pump and were considered the control group. All 168 participants completed the trial. There were no incidences of hypoglycemia and only one incidence of diabetic ketoacidosis, which occurred in the closed-loop group.

The results showed that the closed-loop group remained in the target range for glucose levels (70-180 mg/dL) a greater percentage of time than those in the control group. On average, their time in the target range increased from 61% to 71%, while the control group remained around 59%. In addition, the closed-loop group spent less time with glucose levels above 180 mg/dL or below 70 mg/dL. Throughout the duration of the six-month trial, participants in the closed loop group remained in closed-loop mode (with the system automatically managing glucose monitoring and insulin administration) a median of 90% of the time.

While the closed-loop system is not perfect, these findings show that it improved time spent in the target glucose range, which is desirable in diabetes management. It also reduces the manual tracking and input from individuals with type 1 diabetes in managing the disease. While more research and testing are needed, it is a step in the right direction toward developing what many refer to as an “artificial pancreas.”

Diabetes Research Connection (DRC) is interested to see how this system will continue to advance and improve diabetes management in the future and continues to follow its progress.  These types of devices play an integral role in supporting individuals with T1D and helping them to maintain more normal blood glucose levels. The DRC supports early career scientists in pursing novel research studies geared toward improving understanding, diagnosis, and treatment of T1D with the goal of one day finding a cure. Learn more about these efforts and how to help by visiting http://diabetesresearchconnection.org.

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Improved Transplantation of Islet Organoids May Support Type 1 Diabetes Treatment

One approach to treating type 1 diabetes is transplanting insulin-producing beta cells into the body, or cells that can develop to perform this function. However, there are still many challenges in getting the body to accept these cells without extensive immunosuppression. Even still, the cells often have a limited survival rate.

In a recent study, scientists examined the potential of creating insulin-producing organoids to regulate blood sugar and treat type 1 diabetes. They combined dissociated islet cells (ICs) with human amniotic epithelial cells (hAECs) to form islet organoids, or mini pancreas-like organs. These organoids, which can contain multiple types of cells and cell functions, were transplanted into the portal vein because the area is easily accessible and has a low morbidity rate.

In similar approaches, researchers have been faced with cell death due to poor revascularization of the transplanted cells as well as inflammation. However, in this study, they found that by introducing hAECs, they were able to curb some of these effects. hAECs not only secrete proangiogenic growth factors, but anti-inflammatory growth factors as well including insulin-like growth factors and associated binding proteins. Furthermore, they produce high levels of hyaluronic acid which suppresses tumor growth factor β and stimulates VEGF-A production which supports improved revascularization. They also found that hAECs improved protection of IC-hAEC organoids against hypoxic stress thereby reducing risk of cell death.

Results showed that 96% of diabetic mice who received IC-hAEC organoid transplants achieved normoglycemia within one month. The median rate for this process to occur was 5.1 days. In addition, at one-month post-transplant, the mice showed similar glucose clearance as non-diabetic mice.

While this study has only been performed on mouse models so far, the goal is to achieve similar results in human trials. Additional research and testing are needed to determine if the process is translatable. This approach has the potential to improve management of type 1 diabetes and could lead to a possible cure for the disease if results are sustainable in the long-term.

Though not involved in this study, Diabetes Research Connection (DRC) supports advancements in type 1 diabetes research and treatment by providing critical funding to early career scientists. It is these types of studies that assist in transforming the future of diabetes care. Learn more and support these efforts by visiting http://diabetesresearchconnection.org.

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Rotavirus Vaccine May Reduce Risk of Type 1 Diabetes

There is no single factor that is entirely responsible for the development of type 1 diabetes. Scientists believe that both genetic and environmental factors play a role. One area that they are examining more closely is the impact of enteroviruses. Studies have found that since the introduction of two rotavirus vaccines in 2006 and 2008, the incidence of type 1 diabetes in children has decreased.

A recent study compared data from 2001 to 2017 for nearly 1.5 million infants in the United States. They looked at the incidence rate of type 1 diabetes in those who received the full series of either rotavirus vaccine (pentavalent RotaTeq or monovalent Rotarix), those who received only partial vaccination, and those who were unvaccinated either by parental choice or because the vaccinations had not yet been developed. They also looked at incidence rates among children who received both a rotavirus vaccine and the diphtheria, tetanus, and pertussis (DTaP) vaccines at the same time, and those who received only the DTaP vaccines.

While partial vaccination had no impact on risk of type 1 diabetes, infants who completed the rotavirus vaccine series showed a 33% reduction in risk, with those receiving the pentavalent vaccine experiencing a 37% lower risk. In addition, children who were vaccinated had lower hospital admission rates due to enteroviruses within 60 days of being vaccinated than children who were unvaccinated. According to the study, in terms of type 1 diabetes risk, “Overall, there was a 3.4% decrease in incidence annually in children ages 0-4 in the United States from 2001-2017, which coincides with the vaccine introduction in 2006.”

When the rotavirus and DTaP vaccines were administered together, there was a 56% reduction in risk of developing type 1 diabetes than when DTaP vaccines only were given. This leads scientists to believe that the rotavirus vaccine plays an integral role in risk reduction. While it does not entirely prevent infants from developing type 1 diabetes at some point in their life, it may reduce their risk of the disease.

Previous studies have shown that rotavirus infection may increase the destruction of insulin-producing beta cells in diabetes-prone mice. In addition, children who had multiple rotavirus infections had increased islet antibody levels which may contribute to islet autoimmunity, which in turn is linked to type 1 diabetes risk.

Though more research is necessary including longer longitudinal studies to determine if type 1 diabetes was prevented entirely or only delayed, this study is a step in the right direction toward potentially reducing diabetes risk. Encouraging families to get their children the rotavirus vaccine – which is covered at no cost under most health insurance plans – could be an effective strategy in decreasing risk of type 1 diabetes.

Diabetes Research Connection (DRC) is interested to see how these findings may impact the future of prevention efforts for type 1 diabetes and what additional research will discover. The DRC supports early career scientists in pursing novel research regarding type 1 diabetes including diagnosis, prevention, treatment, and management of the disease. To learn more about current projects and how to support these efforts, visit http://diabetesresearchconnection.org.

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Exploring C-Peptide Persistence in Type 1 Diabetes

In diagnosing diabetes, be it type 1 or type 2, one of the key factors doctors look for is C-peptide levels. Traditionally, scientists have believed that low C-peptide levels indicated type 1 diabetes as the body is unable to produce an adequate supply (if any) of insulin, while higher C-peptide levels were associated with type 2 diabetes as the body made insulin but was unable to effectively use it.

However, a recent study shows that this may not be entirely accurate. In a large cohort study in Scotland, there was a broad range of variability in C-peptide persistence across individuals of different ages and duration of disease. Individuals who were older when diagnosed and were close to age of diagnosis had higher C-peptide levels than those who were adolescents when diagnosed and had been living with the disease for a longer period of time. Scientists believe this may point toward there being multiple genetic networks that impact diabetes risk.

The findings also showed that similar C-peptide levels may be present in individuals with adult-onset type 1 diabetes who did not immediately require insulin treatment as those who were diagnosed with type 2 diabetes. Many people with higher C-peptide levels also have increased amounts of proinsulin, which is a prohormone precursor to insulin. However, the cells do not respond to primary stimuli which could mean that they are in a stunned state. If this is the case, there is a potential that they could recover and once again play an active role in insulin production.

The ratio of proinsulin to C-peptide may also be influenced by genetic risk of diabetes. Both genetics and environmental factors may come into play regarding damage to beta cells and their ability or inability to produce insulin.

This study challenges previous understanding about the differences in type 1 and type 2 diabetes when it comes to diagnosis and treatment. There may be the potential to stimulate pancreatic beta cell function in individuals with type 1 diabetes depending on their levels of proinsulin, insulin, and C-peptide.

Diabetes Research Connection (DRC) is interested to see how this may impact the future of diagnosis and treatment of diabetes. It could certainly lead the way to more in-depth research opportunities, and the DRC provides critical funding to support these types of initiatives. Early career scientists can receive up to $75K from the DRC to pursue novel research projects focused on type 1 diabetes. To learn more, visit http://diabetesresearchconnection.org.

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Could Improving Cell-to-Cell Communication Enhance Cell Replacement Therapy Options for Type 1 Diabetes?

Researchers have been exploring the potential of stem cell therapies for years, however this is a very challenging endeavor because there are many factors that influence cell development, differentiation, and fate. In the case of type 1 diabetes, researchers have been studying methods for preventing the destruction of insulin-producing beta cells, stimulating the generation of new cells, and directing differentiation of stem cells among other strategies.

In a recent study, scientists focused on enhancing cell-to-cell communication in order to influence differentiation of embryonic stem cells. They examined the role of Connexin 43 (Cx43) specifically, which is a gap junction (GJ) channel protein. Scientists found that by using the AAP10 peptide to activate Cx43 GJ channels, they could steer differentiation of cells toward definitive endoderm and primitive gut tube lineages. In turn, with improved communication between cells triggered by the AAP10 peptide, definitive endoderm cells were more likely to become pancreatic progenitors and pancreatic endocrine progenitors.

Pancreatic progenitors (PP) and pancreatic endocrine progenitors (PE) play a role in the development of pancreatic islet cells which produce insulin and glucagon. These are the same cells that the body mistakenly attacks and destroys in individuals with type 1 diabetes. The ability to influence the differentiation of human embryonic stem cells into PPs and PEs may support improved cell replacement therapies for diabetes.

There is still a great deal of research to be done as it is difficult to manipulate the mechanisms of cell communication in order to produce desired results. Scientists are also continuing to investigate whether improved intercellular communication could lead to an increased production of pancreatic islet cells.

Researchers involved in this study include Dr. Wendy Yang, Dr. Laura Crisa, and Dr. Vincenzo Cirulli. Yang’s research is funded by Diabetes Research Connection (DRC) and Crisa and Cirulli are part of the DRC’s scientific review committee. To learn more about the DRC and the funding it provides to support type 1 diabetes research, visit http://diabetesresearchconnection.org.

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Antibody-Drug Conjugate May Help Reduce Allograft Rejection.

Cell transplantation has been an area of focus in developing treatment for type 1 diabetes. Many studies have examined both autologous and allogeneic transplants and the benefits and risks they provide. A major challenge continues to be rejection and the body’s destruction of these cells, whether initially derived from its own cells or not.

However, a recent study found that an anti-CD103 antibody-drug conjugate (M290-MC-MMAF) may reduce pancreatic islet allograft rejection in mice. This drug decreased the amount of CD103+CD8+ effector T cells while at the same time increasing the amount of CD4+CD25+ regulatory T cells. This balance led to improved survival rate of the allograft and supported immunosuppression without causing systemic toxicity. When CD103+CD8+ levels were increased, allograft rejection quickly followed.

While this study has only been conducted in mouse models, it shows potential for pancreatic islet allografts in treating type 1 diabetes. Further research is necessary to determine how this process translates to human cells. M290-MC-MMAF could eventually be used as a therapeutic intervention to reduce risk of allograft rejection in humans.

Diabetes Research Connection (DRC), though not involved in this study, stays abreast of the latest discoveries in the field and supports early career scientists in pursuing novel, peer-reviewed research projects related to type 1 diabetes. Scientists receive funding that is critical to conducting research and improving the diagnosis, treatment, and management of the disease and one day finding a cure. To learn more about current projects and how to support these efforts, visit http://diabetesresearchconnection.org.

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Early Biomarker for Pancreatic Beta Cell Loss Related to Type 1 Diabetes Identified.

For years, researchers have known that pancreatic beta cell death plays a major role in the development of type 1 diabetes. They have been striving to detect this process early on in order to better assess risk for the disease and develop potential treatments to stop progression. When the body destroys insulin-producing beta cells, it is no longer able to effectively manage blood glucose levels resulting in type 1 diabetes (T1D), a condition that currently has no cure.

In a recent study, researchers used diabetic mice and serum samples from individuals with various stages of T1D as well as INS-1 cells and human islets “to detect an early biomarker of T1D-associated beta-cells loss in humans.” The enriched microRNA (miR-204) that they discovered is released by beta cells during cell death and is detectable in human serum. However, it is only present in elevated levels in individuals with T1D and those who are autoantibody positive, not in individuals with type 2 diabetes.

This discovery may play a role in improving early detection of pancreatic beta cell death prior to full onset of T1D. In turn, that may open doors to new research and developments in treatment in order to reduce risk of T1D.

Diabetes Research Connection (DRC) is excited to see what this discovery could mean for the future of T1D diagnoses and prevention efforts. The DRC supports early career scientists in pursuing novel, peer-reviewed research projects focused on the diagnosis, prevention, treatment, and eventual cure of type 1 diabetes. Learn more about current projects and how to support these efforts by visiting http://diabetesresearchconnection.org.

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Could Gluten Impact HbA1c Levels?

Researchers know that type 1 diabetes involves the body’s immune system mistakenly attacking and destroying insulin-producing beta cells, and that this can be affected by autoantibodies and antibodies. However, the body produces antibodies in response to many diseases, including celiac disease.

In a recent study, researchers explored the relationship between patients with celiac disease achieving antibody-negativity versus staying antibody-positive and the potential impact on type 1 diabetes. When individuals with celiac disease stop eating gluten, the body stops producing specific antibodies that react to gluten. Tight management of the disease may produce antibody-negative results during testing. If the person continues to eat some gluten, they will remain antibody-positive.

Scientists compared 608 pediatric patients with type 1 diabetes (T1D) and biopsy-proven celiac disease with 26,833 patients with T1D only. They found that those patients with both diseases who remained antibody-negative had lower HbA1c levels than those who were antibody-positive. The study also showed that, compared to patients with only T1D, those who had both celiac disease and T1D and were antibody-negative had lower total cholesterol, LDL-cholesterol, and frequency of dyslipidemia as well.

Though more research is necessary, achieving constant antibody-negative status may be associated with improved metabolic control and growth and have an impact on HbA1c levels. This could lead the way to advancements in treatment options for individuals with celiac disease and type 1 diabetes and perhaps type 1 diabetes alone as well.

Diabetes Research Connection (DRC) stays abreast of the latest developments in the field and supports early career scientists in pursuing peer-reviewed, novel research studies on type 1 diabetes. It is through these types of projects that researchers learn more about diagnosis, treatment, and prevention of this disease and move closer toward finding a cure. Learn more about current projects and how to support these efforts by visiting 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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Examining the Impact of Intensive Glucose-Lowering Treatment on Hypoglycemia Risk

One of the key indicators in effective diabetes management is HbA1c level. In healthy, non-diabetic adults, the target range is 4% to 5.6%, while in individuals with diabetes, the goal is to maintain an HbA1c level of less than 7%. However, some treatment guidelines aim for achieving levels of 5.6% or less, or between 5.7% and 6.4%.

Striving for these lower HbA1c levels through intensive glucose-lowering therapy may prove more risky than beneficial, though, especially for adults who are considered clinically complex, according to a recent study. These individuals may benefit from less intensive treatment and slightly higher target HbA1c levels to reduce risk of emergency department visits and hospitalizations for severe hypoglycemia.

The study included data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014, and “participants were categorized as clinically complex if 75 years or older or with 2 or more activities of daily living limitations, end-stage renal disease, or 3 or more chronic conditions.” They were considered to be engaged in intensive treatment if their HbA1c level was below 5.6% and they took any glucose-lowering medication, or if their HbA1c level was between 5.7% and 6.4% and they took two or more glucose-lowering medications.

In addition to NHANES data, other population-level studies were included as well when comparing data and outcomes. Overall, overtreatment was estimated to occur in up to 50% of non-clinically complex patients and up to 60% of clinically complex patients.

For the study, 662 nonpregnant adults who had diabetes and maintained HbA1c levels of less than 7.0% were used to represent around 10.7 million adults with diabetes in the United States. Of these participants, 20.1% were age 75 or older, 21.5% were treated intensively, and 32.3% were considered clinically complex. The researchers estimated that over two years, there would be 31,511 hospitalizations and 30,954 emergency department visits for severe hypoglycemia, and that around 4,774 hospitalizations and 4,804 ED visits could be directly attributed to intensive glucose-lowering therapies.

The study found that aggressive treatment of diabetes to achieve lower HbA1c levels could actually have a negative effect on overall health, especially for clinically complex patients who experienced severe hypoglycemic events. It is recommended that many elderly and clinically complex patients avoid intensive treatments and follow relaxed glycemic targets. Recommended HbA1c levels should be evaluated on an individual basis and take into account patient health, comorbidities, and clinical complexity.

There were limitations to this study, and researchers note that “true numbers are likely to much higher” regarding hypoglycemic events and the number that are directly attributable to intensive glucose-lowering therapy.

Type 1 diabetes management is a complex process, and researchers are continually advancing their understanding of the disease and effective treatment options. Diabetes Research Connection (DRC) follows advancements in the field and potential impact on individuals living with T1D.

DRC supports novel, peer-reviewed research studies regarding the diagnosis, treatment, and quality of life for those living with the disease. Learn more about current projects and how to donate to these efforts by visiting http://diabetesresearchconnection.org.

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Could Peripheral T Helper Cells Be Linked to Type 1 Diabetes Risk?

Type 1 diabetes (T1D) is a complex disease. Researchers believe that both genetics and autoantibodies play a role in development of the disease. In individuals with T1D, the immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas. A new study has found that peripheral T helper cells may play a role in initiating this process.

The study showed that children with T1D, as well as those who were autoantibody-positive who developed the disease later on, both had an increase in the amount of peripheral T helper cells circulating in their blood. Researchers believe that much like follicular helper T cells, peripheral T helper cells may also be involved in activating B cells which target against proteins in pancreatic islet cells and contribute to the development of T1D.

The ability to identify children who are at increased risk for the disease due to genetics as well as the elevated presence of peripheral T helper cells may improve options for proactively monitoring and treating T1D. It could also support the development of new immunotherapies for the disease.

More research is necessary to better understand the role of this T-cell subset and how it impacts type 1 diabetes risk and development of the disease as well as how it could improve treatment or prevention options. Though not involved with this study, Diabetes Research Connection (DRC) follows the latest developments and advancements regarding type 1 diabetes understanding, treatment, and prevention.

DRC provides critical funding for early career scientists pursuing novel research studies related to the disease and hopes to one day find a cure. To learn more about current projects or how to help, visit http://diabetesresearchconnection.org.

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Does Timing of Exercise Affect Blood Glucose Levels for Individuals with Type 1 Diabetes?

Regular exercise is an important part of maintaining good health, and this goes for individuals with type 1 diabetes (T1D) as well. However, the question has often risen as to whether the time of day that individuals engage in exercise has an impact on their blood sugar management. A recent study compared results when resistance training was completed in the morning during a fasting state versus in the afternoon after blood sugar had been managed throughout the day.

The randomized study involved 12 participants between the ages of 18 and 50 who had been diagnosed with T1D for a least a year, did not take any medications (aside from insulin) that may impact their blood glucose levels, had no limitations on required exercises, and did not perform shift work. They were asked to keep a log of their food intake and insulin dosage because they were blinded to continuous glucose monitoring.

The results showed that engaging in resistance exercise in the morning (7 a.m.) led to a higher risk of hyperglycemic episodes than exercising in the afternoon (5 p.m.). Blood glucose levels tended to be higher during morning exercise and the 60-minute recovery period as well as during the next six hours. However, with afternoon exercise, blood glucose levels declined during exercise and returned almost to baseline during recovery. There was also less glycemic variability during the six hours post exercise.

It is essential that individuals with type 1 diabetes talk to their doctor before starting or changing their exercise routine, and that they carefully monitor their blood glucose before and after physical activity. Studies like these play an important role in helping individuals with T1D to better manage the disease and improve their quality of life.

Diabetes Research Connection (DRC) stays abreast of the latest developments in the field and supports early career scientists in pursuing novel, peer-reviewed research projects focused on prevention, treatment, and an eventual cure for T1D as well as improvement of quality of life. Learn more about current studies and how to support these efforts by visiting http://diabetesresearchconnection.org.

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Exploring the Potential Impact of Genetics and Infection on T1D Risk

There is no clear, concise explanation for why some people develop type 1 diabetes (T1D) and others do not, or what puts some people at greater risk for the disease. The origins and triggering factors for T1D are something that scientists have been studying for decades. A recent study looks at the possible relationship between genetic risk variants and viral infections and their impact on T1D development.

In some individuals, enteroviruses may trigger or accelerate disease development. However, in others, these same viruses may stimulate a variety of protective factors. Both genetic and environmental factors come into play, and researchers are exploring how to use these findings to improve treatment and prevention of T1D.

Scientists know that the destruction of insulin-producing beta cells plays a role in disease development. Some individuals present with autoantibodies long before T1D develops, and there are still beta cells present in many people even after living with the disease for many years. Yet they are still unsure about exactly what triggers beta cell destruction.

Studies have shown that around 50 percent of T1D risk is heritable. But just because a person carries this risk, does not necessarily mean they will develop the disease. There are around 60 different loci for single-nucleotide polymorphisms (SNP) that are associated with T1D and may contribute to risk.

Researchers believe that enteroviruses may also play a role. Many links have been found between enterovirus infections and the presence of various autoantibodies.  These infections may trigger beta cell autoimmunity in individuals who already have factors that put them at greater risk of developing T1D. By more effectively identifying individuals who have multiple risk factors, scientists may be able to create targeted antiviral treatments or preventive virus vaccines.

There is still a great deal of research to be done regarding the development of and triggers for T1D. Genetics, environment, and infection may all play a role, but their impact differs from person to person. There is also limited insight into factors such as ethnicity and gender, especially when looking at enteroviral etiology.

Though not involved with this study, the Diabetes Research Connection (DRC) contributes to current bodies of research through providing critical funding for early career scientists pursuing projects related to the diagnosis, prevention, treatment, and eventual cure for T1D. Scientists are learning more about the disease every day. Support these efforts by visiting http://diabetesresearchconnection.org.

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Asthma Medication May Help Treat Diabetic Retinopathy

A common complication associated with diabetes (T1D) is diabetic retinopathy. Poor blood sugar control can increase risk of this disease because it impacts the blood flow to the eye by blocking and damaging tiny blood vessels. It can eventually lead to blindness. Symptoms can be very mild and barely noticeable at first, so this is often a condition that is treated in later stages when the effects become more severe.

However, a recent study found that the administration of an FDA-approved asthma medication – montelukast, also known as Singulair – may help reduce damage to blood vessels and nerves in and around the eye. This indication has only been tested in mouse models so far, but because it is already an FDA-approved medication for use in children and adolescents, this may decrease the time it takes to shift into human clinical trials.

Researchers found that the medication suppresses inflammation enough to alter the signaling of inflammatory molecules and prevent pathology, but not enough to compromise the body’s innate immunity. If found effective in human trials, it could be used as a prevention method as well as to treat diabetic retinopathy in its early stages. This could be beneficial to children who are newly diagnosed with type 1 diabetes and even those who have been managing the disease for several years and are at risk for eye disease.

Though not involved with this study, the Diabetes Research Connection (DRC) is interested to see how it progresses and what findings show when used in human subjects. It is encouraging to see a potential new option for reducing risk of diabetic retinopathy and improving quality of life for individuals living with type 1 diabetes.

DRC supports early career scientists in pursuing novel, peer-reviewed research studies aimed at prevention, treatment, and an eventual cure for type 1 diabetes. To learn more about current projects and how to help, visit http://diabetesresearchconnection.org.

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Structured Mealtime Routines May Help Manage HbA1c Levels in Young Children with Type 1 Diabetes

Managing type 1 diabetes (T1D) can be challenging for anyone, but it can be especially difficult for parents of young children with the disease. They must carefully monitor their child’s diet and activity while regularly checking blood glucose levels. A recent study has found that those children who receive preprandial insulin and eat on a regular schedule tend to have improved HbA1c levels.

Researchers analyzed data from 22 Australian children age seven or younger. Their parents tracked the exact amounts and types of food and beverages offered and consumed by their children over a three-day period. They also answered 16 questions regarding mealtime routines and their child’s eating patterns, such as whether they grazed throughout the day or had set snack times and meal times. In addition, it asked about use of preprandial insulin.

The study found that 95% of children used preprandial insulin, and all children ate at least three meals per day. For 81% of children, their parent determined when they were offered food, but the other 19% followed child-led eating patterns. While there was no direct correlation between carbohydrate, protein, or fat intake on HbA1c, researchers did note that HbA1c levels were lower in those children who ate at regular mealtimes as opposed to grazing throughout the day.

Another interesting note was that the children with T1D ate similar diets as those children without the disease. Furthermore, none of the children in the study met the daily recommended vegetable intake, and only 28% ate recommended amounts of lean meats and protein. Additional research is necessary to evaluate the impact of diet quality on diabetes management.

It is these types of studies that provide further insight into improving management of type 1 diabetes. The Diabetes Research Connection (DRC) provides early career scientists with up to $75K in funding to support peer-reviewed, novel research studies focused on prevention, treatment, and management of type 1 diabetes as well as working toward a cure. To learn more and donate to current projects, visit http://diabetesresearchconnection.org.

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Nasal Glucagon Approved to Treat Severe Hypoglycemia

If you or someone you love is living with type 1 diabetes, you know that, in addition to blood sugar becoming too high, having it drop too low is a serious concern as well. When blood sugar falls below 70mg/dL, individuals often start feeling the effects such as shakiness, sweating, chills, lightheadedness, weakness, blurry vision, or tiredness.

If blood sugar continues to drop, it can lead to severe hypoglycemia where the person may be unable to treat their low blood sugar themselves due to confusion, seizures, or loss of consciousness. When this occurs, the individual with T1D often relies on medical personnel or a trained bystander to administer glucagon. Traditionally, glucagon is injected into the arm, thigh, or buttock. However, the medication must first be reconstituted, which involves injecting the contents of the syringe into a vial, mixing it together, then drawing it back into the syringe to inject into the person. In an emergency situation, this can be a lot of steps to follow and there is plenty of room for error.

In an effort to simplify the process, Eli Lilly and Company has manufactured the first ever FDA-approved nasal glucagon, Baqsimi. The device is pre-loaded with 3 mg of glucagon and ready to use for patients age 4 and older. The medication stimulates the liver to release glucose and was found to effectively reverse insulin-induced hypoglycemia based on three studies encompassing more than 200 participants. There were no major safety concerns, and the potential adverse reactions were similar to those of injectable glucagon with the addition of watery eyes and nasal congestion. However, nasal glucagon is not recommended for individuals with pheochromocytoma or insulinoma.

Nasal glucagon provides yet another option for individuals with T1D to quickly – and more easily – treat episodes of severe hypoglycemia. It is simple to use because there is no reconstitution, multi-step processes, or injections necessary. The drug is expected to hit the U.S. market around the beginning of September 2019.

We are excited to see this new product come to market and is interested to see how it impacts diabetes care and management for individuals who experience severe hypoglycemia.

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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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Enteroviruses May Be Linked to Higher Type 1 Diabetes Risk

As with many diseases, type 1 diabetes is triggered by both genetic and environmental factors. There is not a single cause that can be pinpointed when it comes to why insulin-producing beta cells are destroyed by the body. However, researchers are constantly discovering different factors that may contribute to this process. A recent study found that children diagnosed with type 1 diabetes (T1D) may have higher levels of enterovirus A (EV-A) in their gut than children without T1D.

In comparing faeces and plasma viromes and data for a birth cohort of 93 Australian children, results showed that 62 percent of children tested positive for at least one vertebrate-infecting virus. The researchers tested samples for all known vertebrate-infecting viruses, and five EV-A types came back as significantly abundant in children at the onset of T1D diagnosis than in control cases.

Viruses often survive longer in the gut than in the blood, so the prolonged presence of enteroviruses in the gut may increase the risk of these infections spreading to the pancreas. In turn, this may contribute to the body’s immune system attacking and destroying insulin-producing beta cells and triggering T1D.

The study opens doors for additional research regarding EV-A and viral load in general as it relates to T1D. These findings could potentially lead to the development of targeted vaccines for these identified viruses to help protect against the development of type 1 diabetes. It is yet another step toward understanding this complex disease and working toward a cure.

The Diabetes Research Connection (DRC), though not involved in this study, stays abreast of the latest research and discoveries in the field to support future advancements. The DRC provides critical funding to early career scientists to support novel, peer-reviewed studies related to the diagnosis, treatment, and prevention of type 1 diabetes.

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HbA1c Levels May Influence Preterm Birth Risk

Maintaining healthy HbA1c levels is essential for individuals with type 1 diabetes (T1D), but it may be especially critical for women seeking to have children. A recent study out of the Karolinska Institutet in Stockholm found that higher HbA1c levels during the periconceptional period may increase risk of preterm birth.

The study compared incidences of preterm birth for 2,474 babies born to women with type 1 diabetes, and 1,165,216 babies born to women without diabetes. They were all single births; no multiples. The researchers found that, overall, preterm birth occurred in 22.3 percent of babies born to women with T1D verses 4.7 percent of babies to women without diabetes. Broken down even further, the results revealed that the higher the woman’s periconceptual HbA1c level, the higher the risk for preterm birth. When the HbA1c level was below 6.5 percent, there was a 13.2 percent incidence of preterm birth compared to a 37.5 percent incidence when the HbA1c level was at or above 9.1 percent.

However, it is important to note that researchers found, “Preterm birth among women with T1D was strongly linked to periconceptual HbA1c levels, although women whose HbA1c levels were consistent with recommended target values were also at increased risk for preterm birth as well as other adverse pregnancy outcomes.”

This study helps to raise awareness about the risk of preterm birth for women with T1D and the importance of monitoring and managing blood sugar levels. T1D can impact many aspects of an individual’s life, and that includes pregnancy. Gaining a better understanding of these effects can support improved treatment and overall healthcare.

The Diabetes Research Connection (DRC) stays abreast of the latest industry findings and provides critical funding for early career scientists pursuing T1D-related research. Donations from individuals, corporations, and foundations make it possible for these projects to move forward and for innovative research to continue.

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