What tests are used to differentiate between type 1 and type 2 diabetes?

Differentiating Type 1 and Type 2 Diabetes: Diagnostic Testing Approach

The most effective way to differentiate between type 1 and type 2 diabetes is through a combination of autoantibody testing and C-peptide measurement, supplemented by clinical characteristics assessment. 1, 2

Primary Diagnostic Tests

Autoantibody Testing

• Testing for multiple islet autoantibodies is the most valuable laboratory approach for differentiating between type 1 and type 2 diabetes, particularly in cases where clinical presentation is ambiguous 2
• Recommended autoantibodies to test include:
  • Glutamic acid decarboxylase autoantibodies (GAD65) 1
  • Insulin autoantibodies (IAA) 1
  • Tyrosine phosphatase autoantibodies (IA-2 and IA-2β) 1
  • Zinc transporter 8 autoantibodies (ZnT8) 1, 2
  • Islet cell autoantibodies (ICA) 1
• The presence of two or more positive autoantibodies strongly indicates type 1 diabetes 3, 2
• Autoantibodies should be measured in accredited laboratories with established quality control programs 2

C-peptide Measurement

• C-peptide levels assess endogenous insulin production capacity 1, 2
• Lower or undetectable C-peptide levels typically indicate type 1 diabetes 1, 2
• Higher C-peptide levels suggest type 2 diabetes 2
• For accurate results, measure fasting C-peptide when simultaneous fasting plasma glucose is ≤220 mg/dL (12.5 mmol/L) 2

Clinical Characteristics to Consider

• Features most useful in identifying type 1 diabetes include:
  • Younger age at diagnosis (<35 years) 3
  • Lower BMI (<25 kg/m²) 3
  • Unintentional weight loss 3, 2
  • Presence of ketoacidosis 3
  • Glucose >360 mg/dL (20 mmol/L) at presentation 3
  • Rapid progression to insulin dependence 2

Diagnostic Algorithm

1. Initial Glycemic Testing: Perform standard glycemic tests to confirm diabetes diagnosis 1

   • Fasting plasma glucose ≥126 mg/dL (7.0 mmol/L) 3, 1
   • 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during OGTT 3, 1
   • Random plasma glucose ≥200 mg/dL (11.1 mmol/L) with classic symptoms 3, 1
   • HbA1c ≥6.5% (48 mmol/mol) 3, 1

2. Autoantibody Testing: If diabetes is confirmed, test for multiple islet autoantibodies 1, 2

   • Multiple positive autoantibodies strongly indicate type 1 diabetes 3
   • Negative autoantibodies suggest type 2 diabetes but don't rule out type 1 2

3. C-peptide Measurement: Assess endogenous insulin production 1, 2

   • Low/undetectable levels support type 1 diabetes diagnosis 1
   • Higher levels suggest type 2 diabetes 2

4. Clinical Assessment: Consider the "AABBCC" approach 2

   • Age (younger suggests type 1) 3, 2
   • Autoimmunity (presence of autoantibodies suggests type 1) 2
   • Body habitus (lower BMI suggests type 1) 3, 2
   • Background (family history, ethnicity) 2
   • Control (rapid progression to insulin dependence suggests type 1) 2
   • Comorbidities (presence of other autoimmune conditions suggests type 1) 2

Special Considerations and Pitfalls

• Overweight or obese children/adolescents with suspected diabetes should have autoantibody testing to rule out type 1 diabetes 3, 2
• Type 2 diabetes patients may occasionally present with DKA, particularly in ethnic minorities 3
• Patients with type 1 diabetes can also have features classically associated with type 2 diabetes, such as obesity or insulin resistance 2
• Some patients may have features of both types, requiring treatment approaches for both conditions 2
• Hemoglobin variants may interfere with HbA1c testing; use plasma glucose criteria for diagnosis in these cases 3, 1
• Consider monogenic diabetes (MODY) in antibody-negative patients with atypical presentation 1
• Classification of diabetes type is not always straightforward at presentation, and misdiagnosis is common 3

When to Consider Autoantibody Testing

• Adults with phenotypic overlap between type 1 and type 2 diabetes 2
• Children or adolescents with obesity presenting with ketosis or ketoacidosis 3, 2
• Patients with rapid progression to insulin dependence 2
• First-degree relatives of individuals with type 1 diabetes 3
• Individuals with other autoimmune conditions 2

By following this diagnostic approach, clinicians can more accurately differentiate between type 1 and type 2 diabetes, leading to appropriate treatment strategies and improved patient outcomes.