Diabetes-Associated Autoantibodies

Use in combination with another insulin antibody test to determine autoimmune DM.

Useful to establish autoimmune etiology in previously diagnosed T1DM.

  • Determine presence of antibodies to endogenous or exogenous insulin analogues
  • Testing not recommended for patients receiving insulin >2 weeks, as insulin antibody formation may occur

Useful to establish autoimmune etiology in previously diagnosed T1DM.

Useful to establish autoimmune etiology in previously diagnosed T1DM.

Diabetes mellitus (DM) refers to a group of metabolic disorders characterized by hyperglycemia that results from defects in insulin secretion, insulin action, or both. Type 1 DM (T1DM) is less common than type 2 DM (T2DM) and is characterized by insulin deficiency, often resulting from the autoimmune-mediated destruction of insulin-producing cells. The detection of diabetes-associated autoantibodies confirms an autoimmune etiology for that individual.

Indications for Insulin Antibody Testing

Indications for Insulin Antibody Testing
  • Do not order tests individually; order two or more antibodies if pursuing testing 
  • For most cases, order GAD in combination with ≥1 of the following antibodies: IA-2, IAA, ICA, ZnT8
  • Patient should have been previously diagnosed with DM
    • Antibody testing is not useful for the diagnosis of DM
    • Patients should ideally be receiving insulin ≤2 weeks
      • Testing not recommended for patients receiving insulin >2 weeks, as insulin antibody formation may occur (false-positive result possible)
  • Most useful in children or in adults without traditional risk factors for T2DM 
    • Traditional risk factors include BMI ≥25 kg/m2, first-degree relative with diabetes, high-risk race/ethnicity, physical inactivity, etc. (for a full list of traditional risk factors, see Table 2.3 in the Standards of Medical Care in Diabetes—2020).
  • May be useful in difficult adult cases to help differentiate between T1DM or T2DM 

No indication for routine evaluation or management 


Acceptable only for first-degree relatives of a proband with T1DM or in research settings 

Limited Use
  • Differentiate LADA from T2DM 
  • Rule out autoantibodies as a cause of DM in patients with suspected genetic DM types (eg, monogenic DM, maturity onset diabetes of the young [MODY])

GAD, glutamic acid decarboxylase antibody; IA-2, islet antigen-2; IAA, insulin antibody; ICA, islet cell cytoplasmic antibody; LADA, latent autoimmune diabetes of the adult; ZnT8, zinc transporter 8 antibody

 Diabetes Mellitus Type 1 Overview


1.25 million in the United States

Age of Onset

Most common in children but can develop in individuals of any age, especially in late 30s or early 40s


  • Excessive thirst, hunger, and urination
  • Fatigue, nausea, blurred vision
  • Unexplained weight loss
  • Obesity is rare upon initial diagnosis
  • May have other autoimmune disorders


  • Caused by autoimmune-mediated destruction of insulin-producing beta cells of the islets of Langerhans in the pancreas
  • Five major autoantibodies of diagnostic interest
    • Glutamic acid decarboxylase (GAD)
    • Insulin antibodies (IAA)
    • Islet antigen-2 (IA-2)
    • Islet-cell antibodies (ICA)
    • Zinc transporter 8 (ZnT8)
  • Antibodies may be present in individuals years before the onset of clinical symptoms
    • Presence in individuals with diabetes confirms an autoimmune etiology

Test Interpretation


Moderate sensitivity, high specificity in newly diagnosed T1DM

  • Presence of antibodies may decrease with long-term disease
  • Insulin antibody testing loses specificity once patient has been on exogenous insulin for >2 weeks


  • Presence of multiple insulin antibodies (GAD, IA-2, IAA, ICA, and ZnT8) is predictive of T1DM
  • If one autoantibody is found, others should be assayed; the risk of T1DM increases (>90%) if an individual tests positive for two or more autoantibodies
  • For further risk stratification, HLA-DR or HLA-DQ genotyping may be helpful


  • Negative test results do not rule out autoimmune diabetes; autoantibody response varies by individuals
  • Presence of a single autoantibody in the absence of clinical symptoms has low predictive value (1-2% in healthy individuals)
  • Not all individuals with antibodies will develop T1DM
  • Do not use to monitor or diagnose T1DM
  • IAA test does not differentiate between antibodies specific for endogenous and exogenous forms of insulin


Additional Resources