Bloodwork to Diagnose LADA (Type 1.5 Diabetes)
Start with glutamic acid decarboxylase (GAD) antibodies as your primary test, and if negative, proceed to IA-2 and ZnT8 antibodies to confirm or exclude latent autoimmune diabetes in adults. 1, 2
Primary Autoantibody Panel
Order GAD antibodies first as the most frequently positive marker in LADA, present in 70-80% of cases and serving as the primary screening test recommended by the American Diabetes Association 1, 3
If GAD is negative, test IA-2 (insulinoma-associated antigen-2) and ZnT8 (zinc transporter 8) antibodies where available, as these can identify additional cases of autoimmune diabetes 4, 1, 3
Include insulin autoantibodies (IAA) only if the patient has not yet started insulin therapy, as IAA testing becomes invalid once exogenous insulin is administered 4, 1, 3
Standard Metabolic Workup
Measure fasting plasma glucose (≥126 mg/dL diagnostic for diabetes) and HbA1c (≥6.5% diagnostic for diabetes) to establish baseline glycemic control 2
Obtain C-peptide levels to assess residual beta-cell function, particularly useful when the patient is already on insulin therapy 1, 2
C-Peptide Interpretation for Classification
C-peptide <200 pmol/L (<0.6 ng/mL) indicates type 1 diabetes with significant beta-cell loss 4, 1
C-peptide 200-600 pmol/L (0.6-1.8 ng/mL) is indeterminate and consistent with LADA in the appropriate clinical context 4, 1
C-peptide >600 pmol/L (>1.8 ng/mL) suggests type 2 diabetes with preserved beta-cell function 4, 1
Critical pitfall: A "low-normal" C-peptide (e.g., 1.3 ng/mL) should prompt autoantibody testing, as this may represent early LADA rather than type 2 diabetes 5
When to Order This Testing
The American Diabetes Association recommends antibody testing specifically when adults present with:
Age <35 years at diagnosis with features that could be either type 1 or type 2 1, 2
Ketoacidosis or ketosis in an obese patient 1
Rapid progression to insulin dependence despite initial non-insulin therapy 1, 2
Personal or family history of autoimmune diseases 2
Risk Stratification Based on Results
Single positive autoantibody carries only 15% risk of progression to insulin dependence within 10 years and may represent a false positive, particularly in older adults without other type 1 features 3, 6
Two or more positive autoantibodies indicate 70% risk of diabetes progression within 10 years, with 44% risk at 5 years, confirming autoimmune etiology 2, 3
Multiple autoantibodies with dysglycemia (stage 2 disease) carry 60% risk by 2 years and 75% risk within 5 years of requiring insulin 3
Critical Testing Pitfalls to Avoid
Do not order autoantibody testing in patients with clear type 2 phenotype (obese, metabolic syndrome, gradual onset), as the low prevalence of autoimmune diabetes in this population means a positive result is likely a false positive 6
Recognize that 5-10% of true autoimmune diabetes cases are antibody-negative, so negative antibodies in a lean, young adult with acute onset does not exclude LADA 1, 2
Antibody prevalence varies by race: 85-90% in white patients versus only 19% in Black or Hispanic patients with type 1 diabetes, affecting test interpretation 2
Low GAD titers in elderly patients without high-risk HLA genotypes or other antibodies do not predict rapid beta-cell failure 7
Staging System for Clinical Context
Use the three-stage classification when multiple autoantibodies are detected:
Stage 1: Multiple islet autoantibodies + normoglycemia + presymptomatic 2, 3
Stage 2: Islet autoantibodies + dysglycemia + presymptomatic 2, 3
Stage 3: Islet autoantibodies + overt diabetes + symptomatic (this is LADA) 2, 3