Testing for Latent Autoimmune Diabetes in Adults (LADA)
Test for LADA by ordering a standardized islet autoantibody panel—specifically glutamic acid decarboxylase antibodies (GADA), islet antigen-2 antibodies (IA-2A), zinc transporter 8 antibodies (ZnT8A), and insulin autoantibodies (IAA)—in adults with apparent type 2 diabetes who exhibit clinical features suggestive of autoimmune diabetes. 1, 2
When to Test: Clinical Triggers
Order islet autoantibody testing in adults presenting with diabetes who have any of the following features:
- Age at diagnosis <50 years (particularly <35 years) 2, 3
- Unintentional weight loss or lean body habitus (BMI <25 kg/m²) 1, 2
- Rapid progression to insulin requirement despite initial response to oral agents 2, 4
- Ketoacidosis at presentation or short time to insulin treatment 1, 2
- Personal or family history of autoimmune diseases (thyroid disease, celiac disease, vitiligo, etc.) 1, 2
- Poor glycemic control on oral antidiabetic therapy despite adherence 4, 5
The Diagnostic Autoantibody Panel
Order all four standardized islet autoantibodies simultaneously, not sequentially: 2
- Glutamic acid decarboxylase antibodies (GADA/GAD65) - most commonly positive in LADA, present in 70-80% of cases 2, 6
- Islet antigen-2 antibodies (IA-2A) 1, 2
- Zinc transporter 8 antibodies (ZnT8A) 1, 2
- Insulin autoantibodies (IAA) 1, 2
The presence of one or more of these autoantibodies in an adult with diabetes confirms autoimmune diabetes (LADA). 1 Multiple positive autoantibodies indicate higher risk for rapid progression to insulin dependence. 1, 2
Complementary Testing
Alongside autoantibody testing, obtain: 2
- C-peptide levels (fasting and/or 2-hour postprandial) to assess residual beta-cell function 2, 4
- Fasting plasma glucose and HbA1c for glycemic assessment 2
- Consider oral glucose tolerance test if dysglycemia staging is needed 1
Low or declining C-peptide levels combined with positive autoantibodies confirm progressive beta-cell destruction characteristic of LADA. 4, 5
Critical Diagnostic Pitfalls
Single positive antibody has low predictive value - present in 1-2% of healthy individuals without diabetes. 2 Multiple positive antibodies are far more specific for autoimmune diabetes. 1, 2
Antibody-negative LADA exists - approximately 5-10% of patients with autoimmune diabetes may be antibody-negative, so clinical features remain paramount. 2, 6 If clinical suspicion is high despite negative antibodies, manage as LADA based on phenotype (low C-peptide, rapid insulin requirement, lean habitus). 2
Racial variation in antibody prevalence - GAD antibodies are present in 85-90% of white patients with type 1 diabetes but only 19% in Black or Hispanic patients, so negative antibodies do not exclude LADA in these populations. 2
Antibodies decrease over time - testing should occur as close to diagnosis as possible, as autoantibodies may become undetectable in established disease (stage 3). 1, 2 There is no role for repeated antibody measurement once diabetes is established. 6
Use only accredited laboratories - false negatives can occur due to technical issues, so ensure testing is performed in laboratories with established quality control programs. 6
Who Should NOT Be Tested
Do not routinely screen all adults with type 2 diabetes for LADA antibodies due to cost and low yield. 7 Reserve testing for those with the clinical features listed above. 1, 2
Staging After Positive Antibody Results
If autoantibodies are positive, classify the patient using the staging system: 1, 2
- Stage 1: Multiple autoantibodies + normoglycemia + presymptomatic (44% 5-year risk of diabetes)
- Stage 2: Autoantibodies + dysglycemia + presymptomatic (60% 2-year risk, 75% 5-year risk)
- Stage 3: Autoantibodies + overt diabetes + symptomatic (this is LADA)
Next Steps After LADA Diagnosis
Refer to endocrinology for insulin initiation and comprehensive autoimmune screening (thyroid, celiac disease). 6 Consider referral to specialized centers for clinical trial enrollment when multiple autoantibodies are identified. 1