Diagnostic Criteria for Late Onset Type 1 Diabetes Mellitus (LADA)
LADA is diagnosed in adults (typically >30-35 years) presenting with apparent type 2 diabetes who have positive islet autoantibodies—most commonly glutamic acid decarboxylase antibodies (GADA)—combined with clinical features suggesting autoimmune diabetes. 1, 2
Core Diagnostic Criteria
The diagnosis requires three essential elements 3:
- Adult age at onset (typically >30-35 years) 2
- Presence of circulating islet autoantibodies (distinguishes from type 2 diabetes) 1, 3
- Initial insulin independence at diagnosis (distinguishes from classical type 1 diabetes) 3
Specific Laboratory Testing
Autoantibody Panel (Essential)
Order standardized islet autoantibody tests including 1, 2:
- Glutamic acid decarboxylase antibodies (GADA) - most commonly positive
- Islet antigen-2 antibodies (IA-2A)
- Zinc transporter 8 antibodies (ZnT8A)
- Insulin autoantibodies (IAA)
The presence of one or more autoantibodies confirms autoimmune diabetes in adults with apparent type 2 diabetes. 1 However, multiple autoantibodies indicate higher risk of progression to insulin dependence 1.
Standard Diabetes Workup 2
- Fasting plasma glucose ≥126 mg/dL (diagnostic for diabetes)
- HbA1c ≥6.5% (diagnostic for diabetes)
- C-peptide levels to assess beta-cell function (typically low or declining in LADA)
Clinical Features That Trigger Testing
Test for islet autoantibodies in adults with apparent type 2 diabetes who have ANY of the following 1, 2, 4:
- Age at diagnosis <50 years (especially <35 years)
- Unintentional weight loss or BMI <25 kg/m²
- Acute symptoms at presentation
- Ketoacidosis or rapid progression to insulin requirement
- Personal or family history of autoimmune diseases
- Fasting plasma glucose ≥16.5 mmol/L (297 mg/dL) at diagnosis 5
- Poor glycemic control despite oral antidiabetic therapy 6
A clinical prediction rule suggests LADA probability of 0.99 when 1-2 of these features are present: age <50 years, acute symptoms, BMI <25 kg/m², autoimmune disease history, or family history of diabetes. 4
Disease Staging
Use the three-stage classification system for autoimmune diabetes 1, 2:
- Stage 1: Multiple islet autoantibodies + normoglycemia + presymptomatic
- Stage 2: Islet autoantibodies + dysglycemia (FPG 100-125 mg/dL, 2-h PG 140-199 mg/dL, or HbA1c 5.7-6.4%) + presymptomatic
- Stage 3: Islet autoantibodies + overt diabetes by standard criteria + symptomatic
Most LADA patients present at Stage 3 but with slower progression than classical type 1 diabetes 7.
Critical Diagnostic Pitfalls
Single positive autoantibody has limited predictive value - present in 1-2% of healthy individuals and confers low risk for diabetes progression 1, 2. Multiple autoantibodies are more clinically significant.
Autoantibody prevalence varies by race - 85-90% positive in White patients with type 1 diabetes versus only 19% in Black or Hispanic patients 2. Consider clinical features heavily when antibodies are negative in high-risk populations.
Approximately 5-10% of type 1 diabetes patients may be antibody-negative 2, so clinical judgment remains essential when autoimmune diabetes is strongly suspected based on phenotype.
Autoantibodies may decrease or become undetectable over time 1, 2, particularly in long-standing disease, so negative testing does not exclude LADA if clinical features are compelling.
When NOT to Test
Islet autoantibodies are not recommended for routine diagnosis of diabetes in all adults 1. Testing should be reserved for those with clinical features suggesting autoimmune rather than typical type 2 diabetes, as the prevalence of LADA is only 5-10% among adults initially diagnosed with apparent type 2 diabetes 1, 2.
Rule out LADA testing when none of the following are present: fasting glucose ≥15 mmol/L and/or HbA1c ≥10%, 10% weight reduction in 3 months, or BMI <25 kg/m² - probability of LADA approaches zero without these features 4.