Juicebox Podcast: Type 1 Diabetes

Episode #1643 – Grand Rounds: Stephen E. Gitelman, MD
Date: October 3, 2025
Host: Scott Benner
Guest: Dr. Stephen E. Gitelman, Director, Children’s Diabetes Program — UCSF

Episode Overview

This episode of the Juicebox Podcast spotlights Dr. Stephen Gitelman, a leading pediatric endocrinologist and researcher, in a “Grand Rounds” conversation delving into the complexities of type 1 diabetes (T1D). Dr. Gitelman shares his personal and professional journey, discusses the evolving landscape of diabetes research—especially in risk prediction, prevention, and intervention—and provides practical insights for patients and clinicians on supporting those living with T1D. The conversation also explores the interplay of genetics, environmental triggers, mental health, and emerging therapies.

Guest Background and Personal Connection

• Personal Motivation for a Diabetes Career

  • Family history: Multiple relatives, including his grandfather (diagnosed after the discovery of insulin), experienced T1D or autoimmune conditions.
  • Early exposure: “He lived many decades. His life wasn’t easy...I heard how he had to take a train from upstate New York to Boston to pick up his regular allotments of insulin and how my grandmother modified her recipes to make them more appropriate for someone with diabetes.” (Dr. Gitelman, 03:03)
  • Father’s influence: His father, a nephrologist, observed the consequences of poorly managed diabetes; prompted Dr. Gitelman to “try and help the field” (04:23).

• Path into Endocrinology and Pediatrics

  • Intrigued by biology and patient interaction.
  • Found clinical research more fulfilling than pure laboratory work.
  • Maintains involvement with diabetes camps, which he credits as deeply influential: “That one week experience, to me was just revelatory.” (Dr. Gitelman, 56:13)

Key Discussion Points & Insights

1. The Research Landscape: Prediction, Prevention, and Replacement

• Three Pillars of Intervention

  • Prevention: Identify high-risk individuals and intervene before clinical onset.
  • Preservation: Intervene soon after diagnosis to extend the "honeymoon phase."
  • Replacement: Restore lost beta cells for long-term management.
  • “Prevention, preservation, replacement. So if I was going to make a T-shirt for my research team, I think that would be the, that.” (Dr. Gitelman, 09:24)

• Screening & Risk Identification

  • Genetics alone offer limited predictive value; focus has shifted toward screening for autoantibodies and early metabolic changes.
  • Staging T1D:
    • Stage 1: 2+ autoantibodies, normoglycemic, preclinical.
    • Stage 2: Autoantibodies plus mild metabolic changes.
    • Stage 3: Clinical onset, symptomatic, requires insulin.
  • "If you have two or more of these markers, eventually you’re very likely to develop type 1 diabetes… Stage one, two or more autoantibodies... we now call that the onset of type 1." (Dr. Gitelman, 13:08)

2. Environmental Triggers & Epidemiology

• Unpacking Triggers

  • Early feeding practices (breastfeeding vs. cow’s milk), viral exposures, and non-specific inflammation have all been explored, but true causal factors remain elusive.
  • “Maybe the beta cell just isn’t a very robust cell and doesn’t handle stress very well.” (Dr. Gitelman, 18:04)
  • Viral involvement: Elevated incidence at higher latitudes; potential for Coxsackie and other viruses as risk factors; vaccine research ongoing.
  • “There’s a seasonality to type one presentations... so it starts to suggest infection and maybe virus is part of this.” (17:54)

• Complexity of Causality

  • Interplay between genetics and environment creates a “complex stew”—no single causative factor has emerged.
  • Identical twin studies: Even with same genetics, onset and progression can diverge by decades.
  • T1D transcends ethnicity, with rising incidence in various populations worldwide.

3. Theories in the Field

• Accelerator Hypothesis:
  • Obesity and insulin resistance may hasten onset in predisposed individuals.
• Hygiene Hypothesis:
  • Reduced early-life microbial exposure could shift the immune system into an autoimmune-prone mode.
  • “Maybe in a more sterile world we’ve increased our risk for autoimmunity. The risk is increasing not just for type one, but for all autoimmune conditions.” (Dr. Gitelman, 33:20)

4. Notable Breakthroughs & Hopeful Horizons

• Teplizumab and Immune Modulation

  • First therapy shown to delay clinical onset of T1D in at-risk individuals (average delay: 2–3 years).
  • “That’s the first prevention trial that’s worked. We can talk through the details. We probably don’t have time for all that.” (Dr. Gitelman, 40:59)
  • About a third of treated subjects had extended response; long-term responders noted.
  • Therapy is currently burdensome (14-day IV infusions), but work is ongoing to simplify and improve protocols.

• Building on Success

  • Potential for combination therapies: targeting immune system and supporting beta cells.
  • Exploring re-dosing intervals and earlier intervention for even greater effect.
  • "For me, I think we're at the end of the beginning. It's super exciting that tuplizumab has worked. You know, that idea that we learn from what we've done in the past and try and build on it. I mean, now's our time." (Dr. Gitelman, 46:55)
  • COVID-19 research provided reassurance about safety: "We don't think of this drug as immunosuppressive. We think of it as immunomodulatory." (Dr. Gitelman, 47:52)

• GLP-1 Medications

  • Anecdotes and emerging clinical experience suggest possible benefits on insulin requirements, weight, and possibly beta cell function.
  • “There's been some hope that that could be part of the missing puzzle and that if we combined immune therapy with this class of drugs, that's the secret sauce.” (Dr. Gitelman, 51:03)

5. Big Picture: Data, AI, and the Future

• The Role of Shared Data and AI
  • Scientific progress is collaborative, incremental; negative results are as valuable as positive ones.
  • “We just stand on the shoulders of the people that came before us.” (Dr. Gitelman, 22:45)
  • AI considered a promising tool to integrate and synthesize vast, growing data sets for actionable insights.
  • “There's so much information that we're collecting, but it is hard to know how to best sift through it.” (Dr. Gitelman, 38:54)

6. Clinical Care and Patient Support Philosophy

• The Power of Empathy

  • Dr. Gitelman’s diabetes camp experience reframed how he practices and supervises care: “I just happened to maintain my curiosity about diabetes... That one week experience, to me was just revelatory.” (Dr. Gitelman, 56:13)
  • Emphasizes understanding the day-to-day challenges and ensuring that providers appreciate the limitations of current management tools.

• Transitional Care & Extended Pediatric Support

  • Previously, care for young adults with diabetes often shifted too early to adult providers, creating gaps.
  • Now, extending pediatric support to age 25 (due to legislative changes) enhances transitional outcomes: “...we get to support people through those further years. And so I think the baton is passed... in a very different way.” (Dr. Gitelman, 57:51)
  • "You're focusing on this notion of interdependence... I just would not fully let go. It's too important an issue." (Dr. Gitelman, 60:22)

• Supporting Families

  • Critical period: adolescent-early adult years are when self-management drops, and parental support remains vital even amid pushback.
  • “Staying involved and supporting as best you can through those years is super important to their long term success.” (Dr. Gitelman, 60:53)

Memorable Moments & Quotes

• On Living the Questions:

  "It’s this complex stew of things that we have to disentangle to move things forward."
  — Dr. Gitelman (22:38)

• On Hope and Progress:

  "We are getting there. I think the things that we’re asking people to do with their diabetes today is going to get outmoded and get simpler and more definitive."
  — Dr. Gitelman (62:42)

• On Listening to Unusual Patient Stories:

  "Those are the kinds of stories, those are like the breadcrumbs that we were talking about earlier is if we know unusual cases and try and tease apart how and why things are happening there, that might give us important insights to what we do moving forward with a larger trial."
  — Dr. Gitelman (54:54)

Timestamps for Key Segments

• Dr. Gitelman’s Personal Background – 03:03
• Stages and Risk Prediction in T1D – 11:15, 13:08
• Environmental Triggers & the Role of Viruses – 17:02, 17:54, 22:14
• Complexity of Causality and Twin Studies – 25:22
• Accelerator & Hygiene Hypotheses Explained – 30:52, 32:31
• Teplizumab: The Breakthrough – 39:39–46:55
• GLP-1 Medications and Anecdotal Effects – 50:20–54:21
• Transitional Support for Young Adults – 57:45–60:22
• Final Thoughts & Optimism – 62:32

Conclusion

This in-depth Grand Rounds episode offers both hope and realistic perspective on living with, and studying, type 1 diabetes. Dr. Gitelman’s blend of personal motivation, clinical empathy, and research acumen shines through, making this episode a must-listen for families, patients, and healthcare professionals alike. Listeners walk away with an understanding of why T1D remains complex, why new therapies like teplizumab truly matter, and why connection, curiosity, and support are as important as scientific discovery.

“It's taking time, but we are indeed getting there.”
— Dr. Stephen Gitelman (62:46)