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

Diagnostic Criteria for Latent Autoimmune Diabetes in Adults (LADA)

LADA is diagnosed primarily through the presence of islet autoantibodies (particularly GAD antibodies) in adults initially presenting with clinical features resembling type 2 diabetes who do not immediately require insulin therapy. 1

Primary Diagnostic Criteria

LADA diagnosis is based on three essential criteria:

1. Adult age at onset (typically >30-35 years)
2. Presence of islet autoantibodies, particularly:
   • Glutamic acid decarboxylase antibodies (GADA) - most sensitive marker (present in 60-70% of LADA patients)
   • Other autoantibodies that may be tested: islet cell antibodies (ICA), tyrosine phosphatase antibodies (IA-2A), zinc transporter 8 antibodies (ZnT8A)
3. Insulin independence at diagnosis - distinguishing LADA from classic type 1 diabetes 2, 1

Laboratory Testing

• GAD antibody testing should be the primary test, performed in standardized clinical laboratories with established quality control 1
• C-peptide measurement helps assess remaining beta-cell function:
  • <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 1

Clinical Features That Should Prompt Antibody Testing

Standardized islet autoantibody tests are recommended for adults with diabetes who have phenotypic risk factors that overlap with type 1 diabetes 2, including:

• Younger age at diagnosis (<50 years)
• Acute symptoms of hyperglycemia
• BMI <25 kg/mL
• Personal history of autoimmune disease
• Family history of autoimmune disease 3

The presence of at least two of these clinical features has a 90% sensitivity and 71% specificity for identifying LADA, with a negative predictive value of 99% when fewer than two features are present 3.

LADA in the Context of Autoimmune Diabetes Staging

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

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

Diagnostic Pitfalls and Considerations

• LADA represents approximately 5-10% of adults initially diagnosed with type 2 diabetes 1
• Misdiagnosis is common - many LADA patients are initially misclassified as having type 2 diabetes 4
• A single positive antibody test in patients without clinical features suggestive of autoimmune diabetes may represent a false positive 5
• LADA is likely a heterogeneous condition that may represent a mixed population of autoimmune (type 1) and non-autoimmune (type 2) diabetes 5

Diagnostic Algorithm

1. Initial assessment: Evaluate for clinical features suggesting possible LADA

   • Age <50 years at diagnosis
   • BMI <25 kg/m²
   • Acute symptoms of hyperglycemia
   • Personal or family history of autoimmune disease

2. Laboratory testing:

   • If ≥2 clinical risk factors: Test for GAD antibodies
   • If GAD antibodies negative but high clinical suspicion: Consider testing for other islet autoantibodies (IA-2, ZnT8)
   • Measure C-peptide to assess beta-cell function

3. Diagnosis confirmation:

   • LADA confirmed: Adult-onset, positive islet autoantibodies, initially insulin-independent
   • Indeterminate: Consider repeat testing or monitoring for progression

Early identification of LADA is important for appropriate management, as these patients typically progress to insulin dependency more rapidly than those with type 2 diabetes, usually within 3-5 years of diagnosis 1, 6.