What is the recommended test for latent autoimmune diabetes in adults (LADA), also known as late-onset type 1 diabetes?

Testing for Latent Autoimmune Diabetes in Adults (LADA)

Standardized islet autoantibody tests, particularly glutamic acid decarboxylase antibodies (GADA), are the recommended diagnostic test for latent autoimmune diabetes in adults (LADA) or late-onset type 1 diabetes. 1

Diagnostic Approach for LADA

Primary Diagnostic Test

• GADA (Glutamic Acid Decarboxylase Antibodies): The most sensitive and specific test for LADA
  • GADA is particularly useful as approximately 5-10% of White adults who present with a type 2 diabetes phenotype have islet autoantibodies, especially GADA, which predict insulin dependency 1
  • Testing should be performed in an accredited laboratory with an established quality control program and participation in a proficiency testing program 1

Additional Autoantibody Tests

If GADA testing is negative but clinical suspicion remains high, consider testing for other islet autoantibodies:

• Insulin autoantibodies (IAA)
• Islet antigen-2 antibodies (IA-2A)
• Zinc transporter 8 antibodies (ZnT8A) 1

Supporting Tests

• C-peptide levels: Help distinguish between type 1 and type 2 diabetes
  • C-peptide <0.6 ng/mL (<200 pmol/L): Type 1 diabetes pattern
  • C-peptide 0.6-1.8 ng/mL (200-600 pmol/L): Indeterminate
  • C-peptide >1.8 ng/mL (>600 pmol/L): Type 2 diabetes pattern 2

When to Test for LADA

Testing for islet autoantibodies is recommended in the following situations:

1. Adults with phenotypic overlap between type 1 and type 2 diabetes 1
2. Uncertainty about diabetes classification 1
3. Clinical features suggestive of autoimmune diabetes despite adult-onset presentation:
   • Younger age at diagnosis (typically >35 years but younger than typical type 2)
   • Normal or low BMI
   • Personal or family history of autoimmune disorders
   • Rapid progression to insulin dependence despite initial response to oral agents
   • Unexplained weight loss
   • Ketosis or ketoacidosis at presentation 1

Clinical Implications of Diagnosis

• Early identification of LADA is important as these patients progress to insulin dependence faster than antibody-negative type 2 diabetes patients 1
• GADA-positive patients progress to absolute insulinopenia faster than antibody-negative patients 1
• At diagnosis of diabetes in children, absence of all four islet autoantibodies and modest hyperglycemia (HbA1c < 7.5% [58 mmol/mol]) can help identify MODY rather than LADA 1

Important Considerations and Pitfalls

1. False positives: In adults without clinical features of type 1 diabetes, a single positive antibody may represent a false-positive result 3
2. Time to insulin initiation: This should not be used as a defining criterion for LADA as it depends on local clinical judgment and laboratory testing availability 4
3. Test interpretation: The presence of multiple islet autoantibodies increases the specificity of the diagnosis 1
4. Laboratory quality: Islet autoantibody testing should only be performed in accredited laboratories with established quality control programs 1
5. Avoid routine testing: Islet autoantibodies are not recommended for routine diagnosis of diabetes in all patients but should be targeted to those with clinical features suggesting possible autoimmune etiology 1

By identifying LADA early through appropriate autoantibody testing, clinicians can implement proper treatment strategies to preserve beta cell function and improve long-term outcomes for these patients.