What is the primary test for diagnosing Latent Autoimmune Diabetes in Adults (LADA)?

Primary Test for Diagnosing LADA

The primary test for diagnosing Latent Autoimmune Diabetes in Adults (LADA) is glutamic acid decarboxylase antibody (GADA) testing, which should be performed in standardized clinical laboratories with established quality control programs. 1, 2

Diagnostic Approach for LADA

When to Suspect LADA

Consider LADA in adults with diabetes who have:

• Age of onset >35 years
• Initial presentation resembling type 2 diabetes
• BMI <25 kg/m²
• Lack of strong family history of type 2 diabetes
• Poor response to oral hypoglycemic agents
• Personal or family history of other autoimmune diseases 2

Diagnostic Testing Algorithm

1. Primary Test: GADA (Anti-glutamic acid decarboxylase antibody)

   • Most sensitive marker for LADA
   • Present in 60-70% of LADA patients 1, 2
   • Should be performed in an accredited laboratory 1

2. Supportive Tests:

   • C-peptide measurement

     • Helps assess remaining beta-cell function
     • LADA patients typically have lower levels (mean 1.0 ng/mL) compared to type 2 diabetes (mean 5.1 ng/mL) 3
     • Values <1.51 ng/mL have 96% negative predictive value for type 1 diabetes 1
     • Random C-peptide within 5 hours of eating can replace formal stimulation tests 2

   • Other islet autoantibodies

     • ICA (islet cell antibodies)
     • IA-2A (islet antigen-2 antibodies)
     • ZnT8A (zinc transporter 8 antibodies) 1

Interpretation of Results

• GADA positive + normal/low C-peptide: Strongly supports LADA diagnosis 3
• Multiple positive autoantibodies: Associated with more rapid progression to insulin dependence (LADA-type 1) 4
• Single antibody positivity with low titer: Associated with slower progression (LADA-type 2) 4
• C-peptide interpretation guide:

  C-peptide level	Clinical interpretation
  <0.6 ng/mL (<200 pmol/L)	Type 1 diabetes pattern
  0.6-1.8 ng/mL (200-600 pmol/L)	Indeterminate status
  >1.8 ng/mL (>600 pmol/L)	Type 2 diabetes pattern 2

Clinical Pearls and Pitfalls

• Prevalence: LADA represents approximately 5-10% of adults initially diagnosed with type 2 diabetes 2, 1

• Testing Pitfalls:

  • C-peptide should not be measured within 2 weeks of a hyperglycemic emergency
  • Concurrent glucose levels affect C-peptide interpretation
  • Consider repeating the test if glucose was <70 mg/dL at time of measurement 2

• Clinical Implications:

  • Early identification of LADA is important as earlier insulin therapy may better preserve beta-cell function 3
  • GADA testing can prevent misdiagnosis as type 2 diabetes and inappropriate treatment 5
  • Patients with LADA can be staged according to autoimmunity and glycemic status (Stage 1-3) 1, 2

• Cost Considerations:

  • The more expensive GADA testing can be reserved for patients with low or normal random C-peptide levels 3
  • Medicare reimbursement for GADA testing is approximately $28 1

By following this diagnostic approach, clinicians can accurately identify LADA patients and implement appropriate treatment strategies to preserve beta-cell function and improve long-term outcomes.