What tests differentiate between type 1 and type 2 diabetes?

Diagnostic Tests to Differentiate Between Type 1 and Type 2 Diabetes

The most effective tests to differentiate between type 1 and type 2 diabetes include islet autoantibody testing (particularly GAD antibodies), C-peptide measurement, and clinical presentation assessment. 1

Primary Diagnostic Tests

Autoantibody Testing

• Test for islet autoantibodies, with glutamic acid decarboxylase (GAD) as the primary antibody measured. If negative, follow with islet tyrosine phosphatase 2 (IA-2) and/or zinc transporter 8 (ZnT8) where available 1
• Positive autoantibodies strongly indicate type 1 diabetes, as they reflect the autoimmune destruction of beta cells 1
• In individuals not yet treated with insulin, insulin autoantibodies may also be useful 1
• Note that 5-10% of adults with type 1 diabetes may be autoantibody negative 1

C-peptide Testing

• C-peptide levels reflect beta cell function and endogenous insulin production 1
• C-peptide levels <200 pmol/L (<0.6 ng/mL) suggest type 1 diabetes 1
• C-peptide levels >600 pmol/L (>1.8 ng/mL) suggest type 2 diabetes 1
• Intermediate values (200-600 pmol/L) may require additional clinical correlation 1
• For accurate results, test C-peptide when:
  • Patient is receiving insulin treatment
  • Within 5 hours of eating (random sample with concurrent glucose)
  • Not within 2 weeks of a hyperglycemic emergency 1

Clinical Features and Additional Considerations

Age and Clinical Presentation

• Type 1 diabetes traditionally presents in children and younger adults, but can occur at any age 1
• Type 2 diabetes is more common in adults over 35 years, but increasing in younger populations 1
• Classic symptoms of polyuria/polydipsia and weight loss despite normal/increased appetite are more common in type 1 diabetes 1
• Diabetic ketoacidosis (DKA) at presentation strongly suggests type 1 diabetes, though it can occasionally occur in type 2 diabetes, particularly in ethnic minorities 1

Body Mass Index and Other Clinical Factors

• BMI ≥25 kg/m² and absence of weight loss suggest type 2 diabetes 1
• Family history is more strongly associated with type 2 diabetes than type 1 1
• Presence of acanthosis nigricans suggests insulin resistance and type 2 diabetes 1

Diagnostic Algorithm

1. Initial Assessment:

   • Evaluate clinical presentation (age, BMI, symptoms, family history)
   • Check for presence of DKA
   • Confirm diabetes diagnosis with standard criteria (FPG ≥126 mg/dL, 2-h PG ≥200 mg/dL during OGTT, A1C ≥6.5%, or random glucose ≥200 mg/dL with symptoms) 1

2. For adults with suspected type 1 diabetes:

   • Test islet autoantibodies (GAD first, then others if negative) 1
   • If autoantibody positive → Type 1 diabetes
   • If autoantibody negative:
     • Age <35 years → Measure C-peptide
     • Age >35 years → Evaluate for features of type 2 diabetes 1

3. For children and adolescents with overweight/obesity:

   • Test pancreatic autoantibodies to exclude autoimmune type 1 diabetes 1
   • Consider that overweight/obesity can occur in type 1 diabetes 1

Common Pitfalls and Caveats

• Misdiagnosis between type 1 and type 2 diabetes is common, especially in adults 1
• The traditional paradigm that type 1 diabetes occurs only in children and type 2 diabetes only in adults is no longer accurate 1
• In adults without traditional risk factors for type 2 diabetes or younger age, consider autoantibody testing to exclude type 1 diabetes 1
• Hemoglobinopathies and other conditions affecting red blood cell turnover can affect A1C results, making it less reliable for diagnosis in affected individuals 1
• C-peptide testing should not be performed within 2 weeks of a hyperglycemic emergency 1
• Consider monogenic diabetes (MODY) in patients with atypical presentation, especially with strong family history and early onset 1