Beta cell function and ongoing autoimmunity in long-standing, childhood onset type 1 diabetes

Area of Science:

• Endocrinology
• Immunology
• Metabolic Disorders

Background:

• Type 1 diabetes is an autoimmune disease characterized by the destruction of insulin-producing beta cells.
• Long-standing type 1 diabetes typically involves a significant loss of endogenous insulin production.
• Understanding the persistence of beta cell function is crucial for managing the disease and exploring therapeutic strategies.

Purpose of the Study:

• To determine the frequency of residual beta cell function in individuals with long-standing type 1 diabetes.
• To correlate residual insulin secretion with baseline and current islet autoantibody profiles.
• To investigate factors influencing the preservation of beta cell function over time.

Main Methods:

• Measured 2-hour post-meal urine C-peptide:creatinine ratio (UCPCR) in 144 participants with long-standing type 1 diabetes (median 23 years post-diagnosis).
• Defined detectable, minimal, and residual endogenous insulin secretion using established UCPCR thresholds.
• Assessed autoantibodies including GAD (GADA), IA-2A, ZnT8A, and IAA using radioimmunoassay.

Main Results:

• Detectable endogenous C-peptide secretion was found in 35.4% of participants; residual secretion was observed in 4.9% and minimal secretion in 9.7%.
• In samples >10 years post-diagnosis, 65.2% had at least one islet autoantibody (GADA, IA-2A, ZnT8A).
• UCPCR levels correlated with age at diagnosis but were independent of diabetes duration and autoantibody status.

Conclusions:

• Ongoing autoimmunity is present in most individuals with long-standing type 1 diabetes.
• Endogenous insulin secretion persists for many years in individuals diagnosed with autoimmune type 1 diabetes after age 5.
• These findings suggest that some beta cells are protected from continuous autoimmune attack in long-standing type 1 diabetes.