Diabetes Core Update – Special Edition: Early Identification and Delay of Type 1 Diabetes (April 2025)

Podcast: Diabetes Core Update
Date: April 14, 2025
Episode: Special Edition – Early Identification and Delay of Type 1 Diabetes April 2025
Presenters: Dr. Neil Skolnick (Host), Dr. Jay Shubrook (Guest, Touro University)

Overview of the Episode

This special edition focuses on the emerging and crucial topic of identifying individuals at risk of developing type 1 diabetes (T1D) before clinical onset and utilizing recent advancements to delay its onset. The episode explores the distinction between type 1 and type 2 diabetes, pre-clinical disease stages, optimal candidates for screening, and new preventive therapies, highlighting practical insights for frontline clinicians and offering guidance on how to incorporate screening into practice.

Key Discussion Points and Insights

1. Why Early Identification of Type 1 Diabetes Matters

• Traditional Diagnosis: Many T1D diagnoses occur when patients present in diabetic ketoacidosis (DKA), which is traumatic and dangerous (03:42).
  • Quote (Dr. Shubrook, 02:55):
    “Those people who are diagnosed with type 1 diabetes often find out when they're in DKA. This is a traumatic crash landing…”
• Emerging Tools: FDA-approved therapies now exist to delay onset if detected in pre-clinical phases, making early detection actionable.
• Real-life Impact: Example of even physician families missing subtle signs, reinforcing need for proactive strategies (03:42–04:50).

2. Distinguishing Type 1 vs. Type 2 Diabetes

• Etiology:
  • T1D: Autoimmune destruction of pancreatic beta cells; not caused by lifestyle (04:50).
  • T2D: Metabolic, multifactorial, often associated with overweight/obesity and lifestyle factors.
• Misconceptions:
  • Age is no longer a clear diagnostic cue; T1D is increasingly diagnosed in adults and T2D in youth (05:53).
  • Have a ‘healthy suspicion’ for T1D across all ages.
• Diagnosis: Key roles for clinical symptoms (polydipsia, polyuria, weight loss) and lab findings.
  • Quote (Dr. Shubrook, 06:50):
    “Type 1 diabetes, if it goes to the point where they're severely hyperglycemic, they're going to present with the polys...”

3. The Pre-Clinical Stages of Type 1 Diabetes

• Stage 1: Presence of islet autoantibodies, normal glucose.
• Stage 2: Islet autoantibodies, abnormal/prediabetic glucose.
• Stage 3: Diagnostic hyperglycemia with clinical symptoms, i.e. traditional T1D onset (07:52–08:56).
  • Quote (Dr. Shubrook, 07:52):
    “Stage one means you have markers of autoimmunity and normal glucose. Stage two, you have markers… but prediabetes range glucose…”

4. Whom, When, and How to Screen for Preclinical T1D

• Who: First-degree family members of people with T1D; those with personal/family history of autoimmune diseases (09:05).
  • Quote (Dr. Shubrook, 09:05):
    “If you have a first degree family member who has type 1 diabetes, you are at a much higher risk…”
• When: Highest risk for developing autoantibodies in childhood; suggested repeat screens at ages 2, 6, and 10 (10:13).
  • After age 15 with negative antibodies, de novo risk diminishes.
• Frequency: Based on age/initial screen; families often desire repeated screening (10:13–10:56).
• Testing: Use a four-antibody panel (GAD65, ZnT8, IAA, IA-2); simple “type 1 diabetes panel” order often available (14:17).

5. Practicalities and Counseling Around Screening

• Insurance: Generally covered, but options for free community/research-based screening (e.g., TrialNet, Breakthrough T1D) exist (13:31–14:05).
• Education: Critical to communicate both risks and limits, to avoid undue anxiety and misunderstandings (11:53–12:29).
  • Quote (Dr. Skolnick, 13:04):
    “We can reassure our patient there's a better than 90% chance that their family member isn't going to develop type one...”
• Risk Numbers: General population risk is 0.3–0.4%. Father with T1D = 7%, mother = 1.5–3%, sibling = 6–7% (12:29).

6. Management Following Positive Screen

• Interpretation:
  • Zero antibodies: Low risk; consider re-screening based on age.
  • One antibody: Intermediate risk; monitor, not diagnostic.
  • Two or more: High risk; confirm with repeated test (persistent positivity), proceed to oral glucose tolerance test (OGTT) for staging (14:54–16:46).
• Next Steps by Stage:
  • Stage 1: Consider trial enrollment; education.
  • Stage 2: Education plus now an FDA-approved option: teplizumab to delay onset (17:19–18:03).
  • Stage 3: Initiate T1D management.

7. Teplizumab: The New Frontier in Delay

• Mechanism: 14-day infusion, immune-modulatory agent (18:09).
• Efficacy: Delays clinical T1D by 2 years (5-year results), nearly 3 years at 6 years.
  • Quote (Dr. Shubrook, 18:09):
    “Essentially, this is a 14 day infusion… that's given to the person that has been shown to delay the progression to type 1 diabetes by two years in a five year measurement and almost three years at a six year measurement…”

8. Evolving Models & Population Approaches

• Traditional Model: Physician-driven, individual risk-based screening.
• Population-based Proposals: Ongoing studies where all newborns/children are screened; not yet standard, but results suggest higher-than-expected prevalence (19:45–20:54).
• EHR and Outreach: Potential to leverage electronic health records to prompt family-based screening, foster communication, and decrease missed opportunities (21:04–22:55).
  • Quote (Dr. Skolnick, 21:40):
    “Our institution… identifies individuals who are the appropriate age and who have had colonoscopy… one could imagine a time… individuals with type 1 get sent a message that you might consider screening your family members.”

9. Implementation Challenges and Shared Decision-Making

• Barriers: Awareness, persistent myths, time constraints, and need for clinician/patient education.
• Shared Decision-Making: Essential to present data, honor preferences, and avoid pressure or anxiety (23:28–24:28).
  • Quote (Dr. Shubrook, 23:28):
    “Many patients… say, yes, I want to be screened or I want my family screened, but some say no. And I think we have to respect that.”

Notable Quotes & Memorable Moments

| Timestamp | Speaker | Quote | |-----------|---------|-------| | 02:55 | Dr. Shubrook | “Those people who are diagnosed with type 1 diabetes often find out when they're in DKA. This is a traumatic crash landing…” | | 04:50 | Dr. Shubrook | “Type 1 diabetes is an autoimmune disease… Your body attacks the beta cell of the pancreas, so it's autoimmune.” | | 07:52 | Dr. Shubrook | “Stage one means you have markers of autoimmunity and normal glucose. Stage two… prediabetes range glucose…” | | 13:04 | Dr. Skolnick | “We can reassure our patient there's a better than 90% chance that their family member isn't going to develop type one…” | | 18:09 | Dr. Shubrook | “Teplizumab... has been shown to delay the progression to type 1 diabetes by two years in a five year measurement and almost three years at a six year measurement.” | | 21:40 | Dr. Skolnick | “One could imagine a time when… individuals with type 1 get sent a message that you might consider screening your family members.” | | 23:28 | Dr. Shubrook | “Many patients… say, yes, I want to be screened or I want my family screened, but some say no. And I think we have to respect that.” |

Key Timestamps for Important Segments

• 00:02: Episode introduction and context
• 02:55: Why early identification matters; DKA and lived experience
• 04:50: Differentiating T1D and T2D; modern epidemiology
• 07:52: The stages of preclinical and clinical T1D
• 09:05: Who should be screened; method of screening
• 10:13: Frequency and timing of pediatric screening
• 12:29: Risk percentages by family member
• 14:17: The autoantibody panel: which tests to order
• 14:54: What to do with positive screens; counseling and next steps
• 17:19: Actions and options for Stage 2 T1D (preclinical)
• 18:09: Evidence for teplizumab and impact on disease course
• 19:45: Population and community-based screening pilots
• 21:04: EHR-driven approaches to screening and outreach
• 23:28: Barriers to implementation, importance of choice and SDM
• 24:34: ADA initiatives, resources, and upcoming webinars

Final Thoughts and Resources

• ADA Initiatives: Upcoming ADA webinar, new screening advisory group working to support workflow innovation (24:34).
• Action Item for Clinicians: Be proactive in discussing and offering screening where indicated; educate and empower families while mitigating risks of anxiety.
• Broader Message: This approach is new and evolving, with the field expecting major advances in the next years.

For more details and journal content, visit www.diabetesjournals.org