What laboratory tests are used for the diagnosis and management of autoimmune diabetes?

Laboratory Tests for Diagnosis and Management of Autoimmune Diabetes

The diagnosis of autoimmune diabetes requires testing for islet autoantibodies, specifically glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A), insulin autoantibodies (IAA), and zinc transporter 8 (ZnT8A) antibodies, which should be performed in an accredited laboratory with established quality control programs. 1, 2

Diagnostic Laboratory Tests for Autoimmune Diabetes

Islet Autoantibodies

• Glutamic Acid Decarboxylase Antibodies (GADA)

  • Most common autoantibody (~80% of type 1 diabetes patients)
  • Particularly useful for identifying latent autoimmune diabetes in adults (LADA)
  • Should be tested first in adults with suspected autoimmune diabetes 2

• Islet Antigen-2 Antibodies (IA-2A)

  • Present in ~60% of patients with type 1 diabetes
  • Particularly useful when GADA is negative but autoimmune diabetes still suspected 2

• Insulin Autoantibodies (IAA)

  • Present in ~55% of patients with type 1 diabetes
  • Most useful in children before insulin therapy is initiated
  • Important caveat: becomes unreliable after insulin therapy has begun 1, 2

• Zinc Transporter 8 Antibodies (ZnT8A)

  • Present in ~50% of patients with type 1 diabetes
  • Can help identify autoimmune diabetes when other antibodies are negative 2, 3

Additional Diagnostic Tests

• C-peptide with concurrent glucose
  • Helps differentiate between type 1 and type 2 diabetes
  • Levels <200 pmol/L consistent with type 1 diabetes
  • Levels 200-600 pmol/L indeterminate
  • Levels >600 pmol/L consistent with type 2 diabetes
  • Should be measured within 5 hours of eating 2
  • Caution: May be falsely normal during "honeymoon phase" 2

Staging Autoimmune Diabetes

The American Diabetes Association defines three stages of type 1 diabetes progression:

1. Stage 1

   • Multiple islet autoantibodies
   • Normoglycemia
   • No symptoms 1, 2

2. Stage 2

   • Multiple islet autoantibodies
   • Dysglycemia (IFG and/or IGT)
   • No symptoms 1, 2

3. Stage 3

   • Autoantibodies (may become absent)
   • Overt hyperglycemia
   • Symptomatic 1, 2

Testing for Associated Autoimmune Conditions

Patients with autoimmune diabetes should be screened for other autoimmune conditions:

• Thyroid autoantibodies

  • Anti-TPO and anti-thyroglobulin antibodies
  • Most common coexisting autoimmune condition (~20% of children with type 1 diabetes)
  • Should be evaluated shortly after diagnosis 2, 4

• Celiac disease antibodies

  • Tissue transglutaminase and endomysial antibodies
  • Can affect glycemic control through malabsorption 2, 4

Analytical Considerations

• Laboratory Quality

  • Islet autoantibodies should only be measured in accredited laboratories with established quality control programs and participation in proficiency testing 1
  • Different autoantibody assays have varying sensitivity and specificity
  • IAA assays show particularly high interlaboratory variability 1, 2

• Interpretation of Results

  • Single antibody positivity has only 15% predictive value for developing type 1 diabetes within 10 years
  • Multiple antibody positivity has 70% predictive value for developing type 1 diabetes within 10 years 2, 5
  • 1-2% of healthy individuals may have a single autoantibody with low risk of progression to diabetes 2

Monitoring Considerations

• Established Type 1 Diabetes

  • There is currently no role for measurement of islet autoantibodies in monitoring individuals with established type 1 diabetes 1, 2
  • Repeated testing for islet autoantibodies does not guide insulin dosing decisions 2

• Special Circumstances

  • In islet cell or pancreas transplantation, autoantibody testing may help determine if transplant failure is due to recurrent autoimmune disease or rejection 1
  • When a partial pancreas has been transplanted from an identical twin or HLA-identical sibling, appearance of islet autoantibodies may indicate need for immunosuppressive therapy 1

Common Pitfalls and Caveats

• IAA testing becomes unreliable after insulin therapy has begun, as therapeutic insulin induces antibody formation 1, 2

• Clinical presentation alone can lead to misdiagnosis, as up to 40% of adults with type 1 diabetes are initially misdiagnosed as having type 2 diabetes 2

• Obesity should not preclude the diagnosis of type 1 diabetes, as obesity is increasingly common in the general population 2

• C-peptide testing may be falsely normal during the "honeymoon phase" of type 1 diabetes 2

• Absence of all four islet autoantibodies with modest hyperglycemia (HbA1c < 7.5%) in children may indicate MODY rather than type 1 diabetes 1, 2