Type 1 diabetes is an autoimmune illness in which the body attacks the cells that make insulin, called beta cells. For the last few decades, scientists have been researching ways to interrupt this autoimmune process. The two main focuses for this research are preventing or delaying diagnosis and slowing the disease progression for people who are already diagnosed.
TrialNet, a global research effort, has collected data on over 160,000 people with a relative with type 1 diabetes. Their work has been critical for helping researchers understand more about type 1 diabetes and autoantibodies, as well as continuing to work towards the prevention of type 1 diabetes.
Since 2015, the American Diabetes Association, JDRF and the Endocrine Society have classified the onset of type 1 diabetes into a three staged process.1
- Stage 1: no symptoms, normal blood glucose levels but positive for 2 or more type 1 diabetes associated islet autoantibodies
- Stage 2: positive for 2 or more autoantibodies, with abnormal blood sugars but not yet requiring insulin
- Stage 3: glucose levels are out of range, autoantibodies are positive, and now the person has symptoms of type 1 diabetes (the usual excessive thirst, urination, hunger, fatigue, weight loss, etc.). At this stage, treatment with insulin is required.
It’s still unknown what triggers the autoimmune response that causes type 1 diabetes in humans. But if we know that people have autoantibodies that are associated with type 1 diabetes, there are some ways that researchers have found to help prevent their diabetes from progressing as quickly as it would have without intervention. One possibility is a treatment called teplizumab that has been shown to delay the onset of diagnosis in people who were autoantibody positive and in stage 2 of the disease.2
A biopharmaceutical company called Provention Bio is hoping to bring this treatment to market to help prevent and improve outcomes for people at risk for type 1 diabetes. The way that teplizumab works is that it helps modify the cells that are thought to kill off beta cells, CD8+ T lymphocytes, which is a complicated way of saying it helps interrupt the autoimmune process for type 1 diabetes.
In a study conducted by TrialNet, participants were given intravenous infusions of teplizumab daily, over a two-week period. There are some side effects that people experienced, most commonly a rash and a drop in white blood cell count. These resolved and there was not an increase in infections despite the drop in white blood cell count. Out of the 76 participants, 44 were given the teplizumab treatment and 32 were given placebo. Of those treated with teplizumab, the median time to diagnosis of type 1 diabetes was 48.4 months versus 24.4 months for those on the placebo treatment. This is a significant delay.
One of the challenges faced by scientists working to prevent type 1 diabetes is getting people screened for type 1 diabetes autoantibodies and identifying people who do not have any relatives with type 1 diabetes that are autoantibody positive. According to TrialNet, the risk for the general population of getting type 1 diabetes is around 1 in 300. For those with a first degree relative with type 1, the risk increases to 1 in 20. This is why TrialNet has focused on screening first for those with relatives with the type 1 diabetes.
Type 1 diabetes is also often associated with other autoimmune illnesses. Expanding the screening process to this population could help identify more diagnoses earlier. If you are a relative of someone with type 1 diabetes, you may be eligible for free screening through TrialNet. In addition, JDRF offers screening through a program called a T1Detect. You can order a screening kit online for $55 and it will be delivered to your home. The testing kit available to anyone who wants to get tested, not only to those who have a family member with type 1 diabetes.
Another benefit that researchers found is that teplizumab slows down the decline of C-peptide, which has been shown in many studies to be protective of complications and poor outcomes with diabetes.2 This slowing of C-peptide decline can also be helpful in newly diagnosed people with type 1 diabetes and is one of the areas of focus in ongoing teplizumab research. To find out what clinical trials are still enrolling, you can search on clinicaltrials.gov. This is a great way to get involved in clinical research trials and find out what research is going on near you.
Teplizumab is being evaluated by the FDA, and there is hope that we will have access to this immune therapy and others in the years to come. For more information about TrialNet you can check out our recorded CWD Screenside Chat with Dr. Carla Greenbaum from January 2021. For more information about the JDRF T1Detect screening program, you can visit www.jdrf.org/t1d-resources/t1detect/.
References:
- Staging Presymptomatic Type 1 Diabetes: A Scientific Statement of JDRF, the Endocrine Society, and the American Diabetes Association
- An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes
Written and clinically reviewed by Marissa Town, RN, BSN, CDCES
