Testing for LADA (Diabetes 1.5)
Yes, there are specific antibody tests to diagnose LADA, with glutamic acid decarboxylase (GAD) antibodies being the primary and most important test, followed by IA-2 and ZnT8 antibodies if GAD is negative. 1
Primary Diagnostic Tests
Start with GAD (glutamic acid decarboxylase) antibodies as your first-line test, as this is the most frequently positive marker in LADA and the recommended initial test by the American Diabetes Association. 1 This autoantibody is present in the majority of LADA patients and distinguishes autoimmune diabetes from type 2 diabetes. 2, 3
If GAD antibodies are negative but clinical suspicion remains high, proceed to test:
- IA-2 (islet antigen-2) antibodies 1, 2
- ZnT8 (zinc transporter 8) antibodies where available 1, 4
- Insulin autoantibodies (IAA) if the patient has not yet been treated with insulin 1
When to Order These Tests
Standardized islet autoantibody testing is recommended when adults present with phenotypic features that overlap between type 1 and type 2 diabetes. 4 Specifically test when you see:
- Age at diagnosis typically >35 years but <50 years 1, 3
- Unintentional weight loss despite diabetes diagnosis 4, 1
- Ketoacidosis or ketosis in a patient who appears to have type 2 diabetes 1
- Rapid progression to insulin requirement (within 6 months to 5 years) 3, 5
- Lean body habitus (BMI <25 kg/m²) in an adult with new diabetes 1
- Initial insulin independence but clinical features suggesting autoimmune diabetes 6
Additional Confirmatory Testing
C-peptide measurement can help assess residual beta-cell function, particularly if the patient is already on insulin therapy. 1 Obtain a random (non-fasting) C-peptide sample within 5 hours of eating with concurrent glucose measurement. 1
Interpretation:
- <200 pmol/L (<0.6 ng/mL) indicates significant beta-cell loss consistent with type 1/LADA 1
- 200-600 pmol/L (0.6-1.8 ng/mL) is indeterminate 1
600 pmol/L (>1.8 ng/mL) suggests type 2 diabetes 1
Alternatively, stimulated C-peptide after intravenous glucagon can detect impaired beta-cell function even at diagnosis. 3, 5
Critical Diagnostic Pitfalls
Do not order islet autoantibody testing in patients without clinical features suggestive of autoimmune diabetes. 7 In adults presenting with typical type 2 diabetes features (obesity, metabolic syndrome, gradual onset), a single positive antibody likely represents a false-positive result due to low disease prevalence in this population. 7 The test has imperfect specificity, and indiscriminate testing creates a heterogeneous group mixing true autoimmune diabetes with false-positive type 2 diabetes. 7
The presence of multiple islet autoantibodies is more specific than a single antibody and indicates higher risk for progression to insulin dependence. 4, 3 Patients with multiple antibodies typically develop beta-cell failure within 5 years, while those with only GAD antibodies may take longer than 5 years or up to 12 years. 3
Clinical Definition of LADA
LADA is diagnosed based on three criteria:
- Adult age at onset (typically >35 years) 5, 6
- Presence of at least one circulating islet autoantibody (preferably GAD) 5, 6
- Insulin independence for at least 6 months after diagnosis 3, 5, 6
Approximately 10% of adults over age 35 presenting with apparent type 2 diabetes actually have LADA, and this increases to 25% in those under age 35. 3