Endocrine News Podcast: Type 1 Diabetes – Immunotherapies and Early Detection

Episode ENP103 | October 1, 2025
Guest: Dr. Desmond Schatz, Professor of Pediatrics and Medical Director, Diabetes Institute, University of Florida
Host: Aaron Lohr, Endocrine Society

Episode Overview

This episode of the Endocrine News Podcast centers on current advances and challenges in the prevention and treatment of type 1 diabetes, with a specific focus on immunotherapies and the need for early detection and screening. Dr. Desmond Schatz, a leading figure in pediatric diabetes research and care, shares insights from his talk at the Endocrine Society’s Type 1 Diabetes Fellows Series Program. Together with host Aaron Lohr, Dr. Schatz explores the underlying mechanisms of type 1 diabetes, the promise of new immunotherapies like teplizumab, and the vital importance of screening in at-risk populations.

Key Discussion Points & Insights

1. Barriers to Preventing Type 1 Diabetes

• Current State: Type 1 diabetes still cannot be prevented, mainly due to limited understanding.
  • "Right now, we cannot prevent type 1 diabetes, and we have to sort of ask the question, you know, why is that?" — Dr. Schatz [02:24]
• Reasons for Difficulty:
  • Incomplete understanding of disease mechanisms and heterogeneity.
  • Lack of informative biomarkers for early pancreatic changes.
  • Limitations of peripheral blood tests and reliance on animal models.
  • Challenges in enrolling early-stage human study participants.
  • Delayed and limited interest from large pharmaceutical companies.
  • Existing treatments only manage symptoms, not modify disease progression.

2. Is Type 1 Diabetes an Autoimmune 'Suicide' or 'Homicide'?

• Autoimmunity Questioned: Is the destruction self-inflicted (autoimmunity) or triggered by external agents?
  • "Is this a suicide of the pancreas, where your own body's white blood cells ... attack and kill the insulin producing cells?... Or is it a homicide where you actually have something that has now gone in, causing the beta cell to be destroyed..." — Dr. Schatz [04:54]
• Implication: The unclear mechanism impacts targeted treatment development.

3. Disease-Modifying Therapies: Beyond Insulin and Devices

• Current Therapies: Innovations in technology (CGMs, closed-loop systems) and improved insulin therapy have helped, but don’t preserve native beta cell function.
  • “Insulin is not a cure... None of those interventions have led to the preservation of beta cell secretion...” — Dr. Schatz [06:38]
• Goal of Disease-Modifying Therapy: Intervene in the autoimmune destruction, not just treat glucose levels. Focus areas include B/T cell modulation and other immune targets.
  • C-peptide is used as a marker for preserved endogenous insulin production.

4. Staging and Clinical Trials for Immunotherapies

• Stages of Type 1 Diabetes:
  • Pre-Type 1: Genetic risk and single autoantibody presence.
  • Stage 1: Two or more autoantibodies, normal glucose.
  • Stage 2: Two or more autoantibodies with abnormal glucose tolerance.
  • Stage 3: Symptomatic onset.
• Clinical Trials Targeting: Most interventional studies focus on Stage 3, but there’s a push to move therapies earlier.
  • “If you can show... preservation of the ability of the pancreas to make insulin, perhaps we can take that drug... much earlier in the disease...” — Dr. Schatz [08:42]

5. Immunotherapy Advances and Teplizumab

• Short-Term Successes: Several agents (rituximab, ATG, CTLA4-Ig, teplizumab, JAK inhibitors, anti-TNF agents, verapamil, IL-21 antibodies) have shown short-term C-peptide preservation.
  • “All these therapies... have been shown in the short term to be effective.” — Dr. Schatz [11:19]
• Teplizumab Milestone: First FDA-approved drug to delay the clinical onset. Median delay: 2 years.
  • "Compared to placebo... about 54% of teplizumab treated patients were free of diabetes [at 2 years]." — Dr. Schatz [11:19]
  • Differential responder rates point towards the need for precision medicine approaches.

6. Promise and Limits of Teplizumab

• Impact: Proof that intervening in the autoimmune process can delay (and potentially prevent) type 1 diabetes onset.
  • “It’s really the first drug to demonstrate preservation of beta cell function, leading to delay in onset and really potentially in some patients, the prevention of clinical type 1 diabetes.” — Dr. Schatz [15:00]
• Personalized Medicine: Identifying responders, e.g., those with certain biomarkers (ZNT8, HLA, low proinsulin-to-insulin ratio).

7. Urgency of Early Detection & Screening

• Who Should Be Screened: Relatives of people with type 1 diabetes, those with high genetic or autoimmune risk.
• Benefits:
  • Reduces ketoacidosis-related morbidity and mortality at diagnosis.
  • Enables entry into prevention trials and better understanding of disease etiology.
  • “40 to 60% of patients are still diagnosed in diabetic ketoacidosis. And... there is... a morbidity and a mortality.” — Dr. Schatz [17:00]
• Current Screening Tools: TrialNet, ASK study.
• Population-Level Screening: Not yet practical, but may become so with more effective therapies.
  • “Once we develop therapies... then I think we will get to the point where... we’ll certainly get involved with, you know, more generalized screening.” — Dr. Schatz [17:00]

8. Are We on the Way to a Cure?

• Hope vs. Optimism: Dr. Schatz differentiates hope (active pursuit) from optimism (attitude).
  • “There’s a difference between optimism... and hope, which is doing something that we can in order to have an effective outcome.” — Dr. Schatz [20:52]
• Promising Paths:
  • Stem-cell derived islets, gene editing for insulin restoration.
  • The necessity for combination therapies (as in cancer/AIDS) to halt autoimmunity and restore lost function.
  • “Do I think there will be a cure? The answer is yes. Is it going to be tomorrow? The answer is no. But some of the studies ... show incredible promise.” — Dr. Schatz [20:52]

Notable Quotes & Memorable Moments

• On Complexity and Limitations:

  • “We do not know the precise mechanisms to type 1 diabetes... we don't understand the complexity... There's perhaps limited big pharma interest really until now.” — Dr. Schatz [02:24]

• On the Promise of New Therapies:

  • “It’s an exciting time. We’re trying to define who those responders may be. We certainly know that patients who had the ZNT8 marker... some responded better than others.” — Dr. Schatz [15:00]

• On the Need for Broad Inclusion in Research:

  • “I think that the fellows who are attending this and others... can really be part of, of really something exciting.” — Dr. Schatz [13:50]

Timestamps for Important Segments

• [02:24] — Why can’t we prevent type 1 diabetes yet?
• [04:54] — Suicide vs. homicide: Understanding autoimmunity
• [06:38] — Disease modifying therapy concepts
• [08:42] — Clinical trials and staging in type 1 diabetes
• [11:19] — Immunotherapies: current evidence and precision medicine
• [15:00] — What makes teplizumab promising?
• [17:00] — Early detection and screening: who, why, and how
• [20:52] — The pursuit of a cure and future prospects

Conclusion

This episode provides a nuanced exploration of the state of type 1 diabetes research and treatment. Dr. Desmond Schatz highlights both the remarkable progress—such as the approval of teplizumab—and the ongoing necessity for better early detection and precision therapy. The conversation balances candid realism about the challenges facing a cure with invigorating hope, emphasizing the critical role of both scientific advancement and broad-based screening in creating a better future for those at risk for or living with type 1 diabetes.