What are the diagnostic criteria and treatment options for Latent Autoimmune Diabetes in Adults (LADA)?

Diagnosing Latent Autoimmune Diabetes in Adults (LADA)

LADA is diagnosed by the presence of islet autoantibodies (particularly GAD antibodies) in adults initially presenting with type 2 diabetes-like features, with slower progression to insulin dependence than classic type 1 diabetes. 1

Diagnostic Criteria

LADA represents approximately 5-10% of adults who initially present with type 2 diabetes phenotype but have underlying autoimmune pathology 2. The key diagnostic criteria include:

1. Age of onset: Typically over 35 years of age 1
2. Autoantibody presence: Positive for at least one islet autoantibody, particularly:
   • Glutamic Acid Decarboxylase (GAD) antibodies (most common in LADA)
   • Islet Antigen-2 (IA-2) antibodies
   • Insulin autoantibodies 1, 2
3. Initial insulin independence: No requirement for insulin therapy for at least 6 months after diagnosis 3
4. Clinical presentation: Often presents with:
   • Lower BMI than typical type 2 diabetes (often <25 kg/m²)
   • Milder initial hyperglycemia
   • Faster progression to insulin dependence than type 2 diabetes 4

Diagnostic Algorithm

1. Screen for LADA in adults with newly diagnosed diabetes who:

   • Are younger than typical type 2 diabetes patients
   • Have BMI <25 kg/m²
   • Lack strong family history of type 2 diabetes
   • Show poor response to oral hypoglycemic agents
   • Have personal or family history of other autoimmune diseases 1

2. Laboratory testing:

   • Autoantibody testing: GAD antibodies (most sensitive for LADA)
   • C-peptide measurement: To assess beta-cell function
     • C-peptide levels in LADA are typically normal or near normal at diagnosis but decline faster than in type 2 diabetes 1
     • Interpretation of C-peptide:
       • <0.6 ng/mL (<200 pmol/L): Type 1 diabetes pattern
       • 0.6-1.8 ng/mL (200-600 pmol/L): Indeterminate (may suggest LADA)

       • 1.8 ng/mL (>600 pmol/L): Type 2 diabetes pattern 1

3. Confirmatory testing:

   • If GAD antibodies are positive, consider testing for other islet autoantibodies
   • Multiple positive autoantibodies indicate higher risk of rapid progression to insulin dependence 2

Staging of Autoimmune Diabetes

LADA can be understood within the framework of autoimmune diabetes staging 2:

Stage	Characteristics	Diagnostic Findings
Stage 1	Autoimmunity with normoglycemia	Multiple islet autoantibodies, normal glucose levels
Stage 2	Autoimmunity with dysglycemia	Islet autoantibodies, impaired fasting glucose or glucose tolerance
Stage 3	Overt hyperglycemia	Autoantibodies may persist, diabetes by standard criteria

Important Considerations

• Laboratory quality: Islet autoantibodies should only be measured in accredited laboratories with established quality control programs 2
• Differential diagnosis: Consider other forms of diabetes:
  • Type 1 diabetes (more rapid onset, younger age)
  • Type 2 diabetes (negative autoantibodies)
  • MODY (monogenic diabetes, strong family history, specific genetic mutations) 2

Pitfalls to Avoid

1. Misdiagnosis as type 2 diabetes: Leading to inappropriate treatment with sulfonylureas, which may accelerate beta-cell failure in LADA patients 5
2. Delayed insulin initiation: Early insulin therapy is recommended to preserve beta-cell function 1
3. Overreliance on single antibody test: Multiple antibody positivity provides stronger predictive value for rapid progression 2
4. Ignoring C-peptide levels: These provide valuable information about residual beta-cell function and help guide treatment decisions 1

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