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Type 1 Diabetes Prevention Update

A recent article in Nature Reviews: endocrinology gave a summary of the studies in the area of type 1 diabetes prevention to date.  We wanted to share these advances and give a brief explanation.

“Low-dose IL-2 is seemingly safe and expands the number of CD4+CD25+ regulatory T (Treg) cells in children with type 1 diabetes mellitus (T1DM)”

  • Autoimmune disease is, in part, due to malfunctioning regulatory T cells. These cells are responsible for the identification of antigens (things the body identifies as foreign and attacks) when these cells under function (this study identifies IL-s deficiency as a possible case for under-functioning in persons with autoimmune type 1 diabetes)  the body attacks its own cells (Auto-immune disease) administration of low levels of IL-2  reduced antibody rates and reduced damage to beta cells of the pancreas that make insulin. In persons with established type 1 diabetes, this has been shown to reduce beta-cell damage and improve the individual’s ability to generate beta cells.
  • In newly diagnosed children this effect increased the body’s own produced insulin levels.
  • Studies continue into the potential for this as a treatment to delay diabetes onset, reduce treatment needed, and even prevent the development of diabetes and other autoimmune diseases.
  • Limitations: IL-2 has been used as an immunosuppressant in transplant surgery in large doses. Side effects can be severe including severe infection, pulmonary edema, liver failure, and cancer. However, studies have established a safe effective low dose with minimal side effect risk.
  • Currently in phase 2 clinical trials.

“The first study of a monoclonal anti-IL-7R antibody in patients with T1DM finds a dose that reduces effector and memory T cell numbers while preserving Treg cell populations in patients with T1DM”

  • IL-7R is believed to block effector T cell from targeting beta cells, stopping autoimmune attacks on these cells.
  • Mice treated with IL-7R with established diabetes showed a reversal of diabetes and generation of beta cells and insulin production. Mice who were treated with transplanted cells showed no loss of beta-cell insulin production with administration of IL-7R.
  • initial safety studies in humans have shown minimal test-related side effects and positive impact on T cells reducing diabetes-related autoantibody production (kind of like hitting restart on the immune system’s memory allowing it to unlearn that the body’s own cells are foreign), and increasing number and activity of regulatory Tcell productions. Further study continues on the actual impact on autoimmune diseases including type 1 diabetes.

“Post-hoc metabolic outcome analysis of two earlier trials indicates that oral insulin slows the decline of islet metabolic function in high-risk pre-symptomatic individuals.”

  • Studies have shown a sharp reduction in metabolic function of beta cells 1-2 years before diabetes diagnosis and symptom (hyperglycemia) onset.
  • Studies have shown that the administration of oral insulin reduced and delayed this metabolic loss leading to higher levels of insulin production maintenance in persons identified to have genetic markers and/or + GAD autoantibodies correlated to a diabetes diagnosis.
  • Mechanism of action is unclear but is believed to be similar to oral exposure therapy used in allergy treatment in which exposure to an antigen by oral administration reduces the body’s autoimmune response to the antigen.
  • Studies completed on first-generation relatives of persons with type 1 diabetes.
  • Phase 2 clinical trials in progress.

“A successful public health application of islet autoantibody screening was carried out in 2015–2019 in German pre-school children to identify, stage and provide care for children with pre-symptomatic T1DM”

  • A German national health system study conducted widespread auto-antibody testing on over 90,000 children in primary care settings.
  • Children identified to carry positive GAD auto antibodies were enrolled in early diabetes education and support services.
  • Incidence of DKA among children participating in this study and identified as having the risk of type 1 diabetes was less than 5% compared to the general population rate of 20% of children with type 1 being diagnosed in DKA in Germany and 40% in the US. Likely due to education and providers being more vigilant for diabetes onset.
  • However, a similar US study has shown difficulties in getting a broad demographic population, struggling most to capture data from adults, racial and ethnic minorities, parents of children with type 1, and persons in more remote or rural areas. Until these limitations can be overcome the efficacy of screening studies will be reduced or biased. Costs of widespread screenings and a lack of national databases to share patient information are extremely limiting factors to widespread screening.
  • Studies have shown that a 14-day low dose of teplizumab was able to significantly delay the diagnosis of type 1 diabetes in persons at high risk for Type 1 diagnosis (first-generation relatives of persons identified as carrying genetic markers believed to be contributors to diabetes development and those tested positive for antibodies linked to diabetes development) This success points to the benefits of more widespread screening for high risk of diabetes onset in order to prevent and delay onset.
  • Stress levels of caregivers of children diagnosed with diabetes after pre-identification screenings were far lower than stress levels reported by caregivers who did not have the forewarning of potential diabetes onset. This stress reduction leads to better outcomes for children both in diabetes management and overall wellness and in psychosocial and academic development.

The original summary article can be viewed at nature.com with a subscription, and studies referenced in the above information can be found in the references without a subscription.