University Hospitals Offers Infusion Shown to Delay Progression of Type 1 Diabetes

Innovatoins in Diabetes & Metabolic Care | Fall 2024

University Hospitals Cleveland Medical Center is the first health system in Northeast Ohio to offer TZIELD® (teplizumab-mzwv), the only disease-modifying therapy available to delay onset of stage 3 type 1 diabetes (T1D) in adults and children ages 8 and older who have Stage 2 T1D. 

TZIELD received approval from the U.S. Food and Drug Administration in 2022. The novel drug binds to CD3 antigens on the surface of T cells, which may deactivate autoreactive T cells that target pancreatic beta cells. Treatment is administered via intravenous infusion for 14 consecutive days.

The Importance of Screening

Lily Tranchito, DO

Natalie Bellini, MD

“Type 1 diabetes is a life-altering autoimmune disease, so this medication is changing the landscape,” says Lily Tranchito, DO, an endocrinologist at University Hospitals Diabetes & Metabolic Care Center and a Clinical Assistant Professor at Case Western Reserve University School of Medicine. “Before this, if we screened people, there was nothing we could offer. Now we have something that may delay the progression of their disease.”

Parents, siblings and children of individuals with T1D have a 15-fold increased risk of developing the condition. The American Diabetes Association (ADA) and other major organizations recommend screening for first-degree relatives. Individuals with celiac or thyroid disease or rheumatoid arthritis should also be screened. Current guidelines indicate that children with a first-degree relative with T1D should be screened at age 2, between 4 and 6, and between 9 and 11 because those are the times when antibodies can wax and wane.

The UH Diabetes & Metabolic Care team is spreading the word to primary care providers and pediatricians that patients who are found to be at risk will have access to follow-up care and treatment. “We have spots held in our program for individuals who test positive,” says Natalie Bellini, DNP, an Endocrine Nurse Practitioner and Program Director of Diabetes Technology at UH Cleveland Medical Center and Assistant Professor of Medicine at School of Medicine. “We are committed to seeing them within two weeks and working with primary providers to provide ADA Standards of Care in our practice.” 

Stages of Type 1 Diabetes

Before 2015, little was known or published about the development of T1D. “That year, the ADA published an article defining the three stages of the disease based on antibodies that typically develop in early childhood,” Bellini says. “If a person has two of the four positive antibodies, they are staged based on their glucose.”

In stage 1 T1D, there are no glucose fluctuations, even after a carbohydrate load. In stage two, the person has glucose fluctuations after a glucose load, but the fluctuations are not severe enough to need insulin. The first two stages are non-symptomatic. stage 3 T1D is defined by higher glucose and the need for lifelong insulin replacement. 

“If an individual has two or more positive antibodies at the time of screening, their lifetime risk of developing T1D approaches 100 percent,” Bellini says. “Five years after these antibodies are detectable, the probability of progressing from stage 1 T1D to stage 3 T1D is 44 percent. At 10 years, it is 70 percent.” 

The four antibodies are:

• Insulin autoantibodies
• Glutamic acid decarboxylase 65 autoantibodies
• Islet antigen-2 antibodies
• Zinc transporter 8 autoantibodies 

“These antibodies may be detected years before a person develops clinical type 1 diabetes,” Dr. Tranchito says. “We hope to draw attention to the benefit of early screening and make people aware that we will see them and develop a plan for monitoring and treatment even if their blood glucose levels are not currently elevated.”

Reducing Risk of Serious T1D Complications

As many as 40 percent of people with the condition do not know they have T1D until they experience a life-threatening hyperglycemic event such as diabetic ketoacidosis (DKA). DKA develops when the body is unable to produce enough insulin, causing ketones to build up in the blood and collect in the urine. 

“DKA is debilitating,” Dr. Tranchito says. “It can cause long-term brain changes, affect glycemic control over time and increase the risk of morbidity and mortality of T1D. When people are aware they have these antibodies, and we are monitoring their risk progression, we can reduce the risk of DKA from 21 to 56 percent down to almost zero.” 

A Hopeful Advancement

The first University Hospitals patient to receive TZIELD is doing remarkably well. The UH Diabetes & Metabolic Care team will continue to follow her hemoglobin A1C and track her glucose trends via a continuous glucose monitor, and results of treatment will vary.

There is no way to predict how long after infusion a person will develop symptomatic stage 3 T1D, in part because it is impossible to know how long patients have been experiencing increased glucose levels at the time of initial screening. Still, there is reason for hope.

“This is the first time we have been able to offer an intervention that may slow T1D progression and improve long-term risk profiles,” Dr. Tranchito says. 

For more information, contact Dr. Tranchito at Lily.Tranchito@UHhospitals.org or Natalie Bellini at Natalie.Bellini@UHhospitals.org. 

Contributing Experts:
Lily Tranchito, DO
Endocrinologist
University Hospitals Diabetes & Metabolic Care Center
University Hospitals Cleveland Medical Center
Clinical Assistant Professor
Case Western Reserve University School of Medicine

Natalie Bellini, DNP, FNP-BC, BC-ADM, CDCES 
Endocrine Nurse Practitioner and Program Director of Diabetes Technology
University Hospitals Diabetes & Metabolic Care Center
University Hospitals Cleveland Medical Center
Assistant Professor of Medicine
Case Western Reserve University School of Medicine