A New Era for Type 1 Diabetes: Delaying the Disease in Children Before Symptoms Start

The story of a type 1 diabetes (T1D) diagnosis typically begins with a crisis: a child in the emergency room with excessive thirst, weight loss, and the immediate, life-altering start of insulin therapy.

Today, UCSF is changing that story from crisis response to prevention and preparedness.

A First-of-its-Kind Therapy

This shift is driven by a breakthrough therapy called Teplizumab (or Tzield). In 2022, it became the first-ever drug approved by the FDA to delay the onset of symptomatic T1D.

This approval marked the culmination of decades of research, with the UCSF Division of Pediatric Endocrinology playing an instrumental role in the foundational science and clinical trials that made this therapy possible.

A National Leader in Early Intervention

The UCSF At-Risk for T1D Clinic is the clinical home for this new approach. As the second busiest center in North America for Teplizumab infusions, the clinic is helping lead a national shift toward identifying and treating T1D before symptoms start.

We spoke with Stephen Gitelman, MD, director of UCSF's Pediatric Diabetes Program and lead investigator for UCSF’s Teplizumab trials, about the impact of his work and what comes next.

The Gift of Time: What Delaying T1D Means for Families

Teplizumab can delay the need for insulin by an average of two years, and sometimes much longer. What does this mean for a child and their family, especially during critical developmental years?

Delaying diabetes symptoms is invaluable. From a clinical perspective, diabetes care and technology are evolving so rapidly that the average delay of two or three years with teplizumab therapy means a patient will face the disease with better tools when they do progress. Over a third of people who received teplizumab have remained free from the development of clinical T1D for over seven years, and we continue to monitor them.  

A delay in diabetes onset can have profound benefits at any age, giving an individual more time to grow and mature before they (and their family) have to take on the complexity of managing clinical diabetes. These tasks include careful attention to carbohydrate intake and delivering the appropriate amounts of insulin to match meals, with adjustments for exercise and glucose levels.

The delay in onset of clinical disease can be particularly helpful for younger children, who may have more unpredictable daily routines and not yet have the skills to fully communicate with their care providers.

Learning A Child is At Risk

How do families typically discover that their child is at risk for T1D and could benefit from Teplizumab?

Typically, families have an existing family member with T1D, and we inform them about autoantibody screening. This screening is critical, as an unaffected sibling has a lifetime risk for T1D that is 10 to 15 times higher than that of the general population.

Families can get screening at no cost through the NIH-sponsored study TrialNet, which we are a part of, or other programs such as ‘ASK’ (Autoimmune Study of Kids). Samples can often be obtained at home via a fingerstick, or families can get a kit to bring to a local laboratory to have blood drawn and shipped for analysis.

However, in most cases, new-onset T1D occurs in an individual who has no family history. We are now working to raise screening awareness in the general population and incorporate T1D screening into routine well-care visits. We are starting by focusing on individuals and families with other autoimmune diseases, like thyroid or celiac disease, or other conditions associated with a higher risk for T1D, like trisomy 21 or Turner syndrome.

What are the biggest barriers for families seeking this treatment?

The biggest barrier is the treatment program itself: daily IV infusion for 14 consecutive days. Families have to weigh the risk versus the benefit. They may not have the time to take on the infusions, or they may weigh the benefits differently than our diabetes team does.

There is also uncertainty regarding how long the delay in progression will last for a given individual. We’ve seen some patients go more than 10 years after this infusion, while some progress to clinical diabetes in the ensuing months. We review all these short- and long-term considerations when consulting with families.

What is the long-term vision for the At-Risk for T1D Clinic?

We want to continue to increase screening in the general population. Even if individuals found to be at risk elect not to pursue Teplizumab, we want to engage them in ongoing monitoring, with further assessment of the autoimmune response and assessment of insulin-producing beta cell function over time. This allows us to catch the disease at its earliest, silent stages, and help prevent a child from having diabetes first appear as a crisis requiring hospitalization, such as in diabetic ketoacidosis.