What is the role of antibody testing in diagnosing and managing type 1 diabetes?

Role of Antibody Testing in Type 1 Diabetes

Islet autoantibody testing is not recommended for routine diagnosis of diabetes but is valuable for classifying diabetes in adults with phenotypic overlap between type 1 and type 2 diabetes when the type is uncertain. 1

Primary Uses of Antibody Testing

• Standardized islet autoantibody tests are recommended for classification of diabetes in adults when there is uncertainty about whether a patient has type 1 or type 2 diabetes 1, 2
• Antibody testing helps identify latent autoimmune diabetes in adults (LADA), which affects approximately 5-10% of White adults who present with a type 2 diabetes phenotype but have islet autoantibodies (particularly GADA) 1
• Multiple positive autoantibodies strongly indicate autoimmune etiology and predict faster progression to insulin dependence 2, 3
• Testing is valuable for research purposes and in identifying high-risk individuals for clinical trials of preventive therapies 1

Types of Antibody Tests

• Five main islet autoantibodies are clinically relevant 1, 4:
  • Islet cell cytoplasmic autoantibodies (ICA)
  • Insulin autoantibodies (IAA)
  • Glutamic acid decarboxylase autoantibodies (GADA)
  • Insulinoma-associated antigen-2 autoantibodies (IA-2A)
  • Zinc transporter-8 autoantibodies (ZnT8A)
• Quantitative assays for specific autoantibodies have generally replaced the older islet cell antibody (ICA) test 1

Risk Stratification

• The presence of multiple autoantibodies significantly increases risk of developing type 1 diabetes 1, 5:
  • Single autoantibody: 15% risk within 10 years 1
  • Two or more autoantibodies: 70% risk within 10 years 1
• Antibody testing allows staging of type 1 diabetes 1, 3:
  • Stage 1: Multiple autoantibodies with normoglycemia (presymptomatic)
  • Stage 2: Autoantibodies with dysglycemia (presymptomatic)
  • Stage 3: Clinical diabetes with overt hyperglycemia (symptomatic)

Screening Recommendations

• Islet autoantibody testing is not recommended for routine screening in the general population 1
• Screening may be considered in research settings or as an option for first-degree relatives of individuals with type 1 diabetes 1
• The risk of developing type 1 diabetes in first-degree relatives is approximately 5%, which is 15-fold higher than the general population risk 1
• Only about 15% of individuals with newly diagnosed type 1 diabetes have a first-degree relative with the disease 1

Practical Clinical Approach

• For suspected type 1 diabetes without classic presentation, start with GAD antibody testing, followed by additional antibodies if needed 3
• In adults with phenotypic overlap between type 1 and type 2 diabetes, test for multiple autoantibodies for better differentiation 2, 3
• C-peptide measurement complements antibody testing by assessing endogenous insulin production capacity 2, 3

Important Caveats and Pitfalls

• Antibody testing should only be performed in accredited laboratories with established quality control programs 2, 3
• As many as 1-2% of healthy individuals may have a single islet autoantibody and are at low risk of type 1 diabetes 1
• Autoantibodies may not be detectable in all type 1 diabetes patients, particularly in older adults 2, 3
• Certain HLA-DQB1 alleles (B106:02, B106:03, or B1*03:01) are mostly protective against type 1 diabetes but not against developing islet autoantibodies 1
• A two-step screening approach (first testing for GADA and IA-2A, then ICA and IAA in positive individuals) may be more practical and cost-effective 6

Future Directions

• As preventive therapies for type 1 diabetes emerge, antibody testing may become more clinically relevant 4, 7
• Teplizumab has shown promise in delaying clinical onset of type 1 diabetes in high-risk individuals identified through antibody testing 1
• Combining genetic risk scores with autoantibody testing may improve risk prediction 1