Differentiating Between Type 1 and Type 2 Diabetes Through Testing
The most reliable diagnostic approach to differentiate between type 1 and type 2 diabetes is through a combination of C-peptide measurement and autoantibody testing, with C-peptide values below 80 pmol/L (<0.24 ng/mL) strongly indicating type 1 diabetes. 1
Key Diagnostic Tests
Primary Diagnostic Tests
C-peptide measurement
- Type 1 diabetes: Low or undetectable levels (<80 pmol/L or <0.24 ng/mL) 1
- Type 2 diabetes: Normal or elevated levels
- Important notes:
- Must be measured prior to insulin discontinuation in insulin-treated patients
- Should not be tested within 2 weeks of hyperglycemic emergency
- Intermediate values (200-600 pmol/L) may occur in both types 1
Autoantibody testing
- Type 1 diabetes: Positive for one or more autoantibodies (GAD, insulin, islet antigen 2) 2
- Type 2 diabetes: Typically negative for autoantibodies
- The American Diabetes Association identifies three stages of type 1 development:
- Stage 1: Multiple autoantibodies with normoglycemia
- Stage 2: Multiple autoantibodies with dysglycemia
- Stage 3: Clinical diabetes with symptoms 2
Clinical Features to Guide Testing
The AABBCC Approach 1
- Age: <35 years suggests type 1 diabetes
- Autoimmunity: Personal or family history of autoimmune disease
- Body habitus: BMI <25 kg/m² suggests type 1 diabetes
- Background: Family history of type 1 diabetes
- Control: Inability to achieve glycemic goals on non-insulin therapies
- Comorbidities: Treatment with immune checkpoint inhibitors
Type 1 Diabetes Features
- Younger age at diagnosis (<35 years) 1
- Lower BMI (<25 kg/m²) 1
- Unintentional weight loss 1
- Presence of ketoacidosis 1
- Glucose >360 mg/dL (20 mmol/L) at presentation 1
- Rapid and symptomatic onset with polyuria, polydipsia 2
- Approximately one-third present with diabetic ketoacidosis 2
Type 2 Diabetes Features
- Increased BMI (≥25 kg/m²) 1
- Absence of weight loss 1
- Absence of ketoacidosis 1
- Less marked hyperglycemia 1
- Non-White ethnicity 1
- Family history of type 2 diabetes 1
- Longer duration and milder severity of symptoms 1
- Features of metabolic syndrome 1
- Gradual and often asymptomatic onset 2
Diagnostic Algorithm
Initial assessment:
- Measure standard diagnostic criteria (fasting glucose ≥126 mg/dL, 2-hour OGTT ≥200 mg/dL, HbA1c ≥6.5%, or random glucose ≥200 mg/dL with symptoms) 2
- Assess clinical features using AABBCC approach
Laboratory testing:
- Measure C-peptide levels
- Test for diabetes-related autoantibodies (GAD, insulin, islet antigen 2)
Interpretation:
- Type 1 diabetes: Low C-peptide (<80 pmol/L) AND/OR positive autoantibodies
- Type 2 diabetes: Normal/high C-peptide AND negative autoantibodies
- Indeterminate cases: C-peptide 200-600 pmol/L requires clinical correlation
Common Pitfalls and Caveats
- Misdiagnosis is common: Up to 40% of adults with new type 1 diabetes are misdiagnosed as having type 2 diabetes 1
- Age is not definitive: Both types can occur at any age, though type 1 is more common in younger individuals and type 2 in older individuals 1
- C-peptide timing: Values may be misleading if measured within 2 weeks of hyperglycemic emergency 1
- Intermediate C-peptide values (200-600 pmol/L) can occur in both type 1 and insulin-treated type 2 diabetes, particularly in people with normal/low BMI or long disease duration 1
- Ketosis-prone type 2 diabetes: Some patients with type 2 diabetes (particularly ethnic minorities) may present with ketosis despite having type 2 diabetes 1
- Overlapping features: Some patients may have features of both type 1 and type 2 diabetes 1
- MODY confusion: Maturity-onset diabetes of the young may be misdiagnosed as type 1 diabetes 1
When diagnostic uncertainty persists despite testing, careful monitoring and education are essential so that appropriate treatment can be rapidly initiated if glycemic control deteriorates 1.