Diabetes Dialogue: The Push for Early-Stage T1D Screening and Treatment, With Linda DiMeglio, MD, MPH

Welcome back to Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives!

In this episode of Diabetes Dialogue recorded on-site at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2026 in Las Vegas, Nevada, cohosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, interview Linda DiMeglio, MD, MPH, professor of pediatrics and division chief at Indiana University School of Medicine, following her plenary keynote and receipt of the Ellen Garber Award. DiMeglio outlines her broad work in type 1 diabetes research, including prevention strategies, beta cell preservation, diabetes technology, TrialNet leadership, and neurocognitive studies in young children living with diabetes.

The discussion centers on early-stage type 1 diabetes, with DiMeglio reviewing the evolving framework of risk identification and staging, from genetic predisposition and single autoantibody positivity through stage 1, stage 2, and stage 3 disease. She highlights the growing momentum behind both general population and family-based screening, emphasizing the importance of early detection not only to prevent diabetic ketoacidosis but also to enable timely intervention with disease-modifying therapies. She notes the recent expansion of teplizumab approval down to age 1 for stage 2 disease as a major milestone and describes the broader therapeutic goal as ultimately ending insulin dependence for people living with type 1 diabetes.

DiMeglio and the hosts discuss how the field has shifted significantly over the past decade, particularly with the reframing of “cure” as a combination of multiple targeted approaches rather than a single intervention. She underscores the importance of combination immunotherapy strategies, citing recent TrialNet work using rituximab followed by abatacept, as well as the need for more personalized approaches based on individual disease etiology and immune characteristics. She also stresses the need for better intermediate endpoints beyond the traditional 2-year C-peptide model to accelerate therapeutic development and trial efficiency.

The group also examines the increasing role of patient and family perspectives in clinical trial design, particularly through TrialNet’s community advisory board, which DiMeglio believes will improve recruitment and trial execution. They discuss the broader implications of immune-modifying therapies in type 1 diabetes, including parallels with oncology treatment models and the potential for these advances to inform management strategies for other autoimmune diseases. DiMeglio also reflects on how these therapies are reshaping endocrinology practice itself, requiring clinicians to become more familiar with immunomodulation, cytokine management, and interdisciplinary care.

A major focus of the conversation addresses the complexity of autoantibody interpretation, particularly around GAD antibodies and low-titer positivity. DiMeglio emphasizes that a single positive islet autoantibody test should never be considered definitive and should always be repeated, ideally in a separate gold-standard laboratory such as TrialNet. She explains that antibody specificity varies by type and titer, with higher titers often offering greater diagnostic confidence, while acknowledging ongoing uncertainty around interpretation in adults, diverse populations, and long-standing diabetes. The hosts also discuss the practical challenges of coding, insurance coverage, and patient counseling as early-stage diabetes diagnosis becomes more common.

The episode concludes with a discussion of emerging questions around antibody fluctuation over time, circadian variation in antibody measurements, and the role of genetic screening. DiMeglio notes that antibody status may shift over years and may even vary by time of day, introducing additional complexity into monitoring strategies. While genetic risk screening remains promising, she explains that large-scale antibody-based population screening may currently be more practical from a public health perspective. She closes by reinforcing that although much remains nuanced and unresolved, the field is rapidly advancing toward earlier intervention, more individualized treatment, and a fundamentally different future for type 1 diabetes care.

Editors’ Note: Isaacs reports disclosures with Dexcom, Abbott, Lilly, Novo Nordisk, Medtronic, Insulet, and others. Bellini reports disclosures with Abbott Diabetes Care, MannKind, Povention Bio, and others. DiMeglio reports disclosures with Amgen, Lilly, Mannkind, Medtronic, Merck, Ascendis, and others.

References

1. DiMeglio L. Early-Stage Type 1 Diabetes: Screening, Monitoring, Treatments and Future Directions (Alan J. Garber, MD Lectureship). Presented at the American Association of Clinical Endocrinology Annual Meeting 2026, Las Vegas, NV. April 22-24, 2026.