What Have Slow Progressors Taught Us About T1D-Mind the Gap!

Area of Science:

• Immunology
• Endocrinology
• Metabolic Diseases

Background:

• Islet autoimmunity often presents early in life, with ~70% developing type 1 diabetes (T1D) within 10 years.
• A significant portion of individuals with high-risk autoantibodies progress very slowly, remaining diabetes-free for decades.
• Recent genetics indicate ~50% of T1D is diagnosed in adulthood, posing a diagnostic and pathogenic puzzle.

Purpose of the Study:

• To review the phenomenon of slow progression from islet autoimmunity to clinical diabetes.
• To explore the characteristics of slow progressors with high-risk autoantibody profiles.
• To address the gap in understanding adult-onset T1D pathogenesis and identify at-risk adults.

Main Methods:

• Review of existing literature on islet autoimmunity and type 1 diabetes progression.
• Analysis of birth cohort studies and recent genetic findings.
• Discussion of the discrepancy between slow progressors and adult-onset T1D cases.

Main Results:

• The rate of progression from islet autoimmunity to clinical diabetes is highly variable and unpredictable.
• Slow progressors with high-risk autoantibodies represent a distinct group that challenges current models of T1D development.
• The high incidence of adult-onset T1D suggests a need for further research into adult populations for identifying at-risk individuals.

Conclusions:

• Slow progressors with islet autoimmunity are a critical focus for understanding T1D pathogenesis.
• The current understanding of adult-onset T1D is incomplete, necessitating longitudinal studies in the general adult population.
• Identifying and characterizing both rapid and slow progressors in adults is essential for future T1D research and management.