DRC & Research News

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.

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.

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.

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.