Differentiating Type 1 from Type 2 Diabetes
Use the AABBCC clinical approach combined with islet autoantibody testing and C-peptide measurement to distinguish type 1 from type 2 diabetes, recognizing that misdiagnosis occurs in up to 40% of adults with new-onset type 1 diabetes. 1
Initial Clinical Assessment: The AABBCC Approach
The American Diabetes Association recommends the following systematic evaluation 1:
- Age: Consider type 1 diabetes in patients <35 years old 1
- Autoimmunity: Assess for personal or family history of autoimmune diseases or polyglandular autoimmune syndromes 1
- Body habitus: BMI <25 kg/m² suggests type 1 diabetes 1
- Background: Family history of type 1 diabetes points toward type 1 1
- Control: Inability to achieve glycemic goals on non-insulin therapies indicates type 1 1
- Comorbidities: Recent treatment with immune checkpoint inhibitors can cause acute autoimmune type 1 diabetes 1
Key Clinical Features Distinguishing Type 1 Diabetes
Most discriminatory features for type 1 diabetes include 1:
- Age at diagnosis <35 years with BMI <25 kg/m²
- Unintentional weight loss
- Ketoacidosis at presentation
- Glucose >360 mg/dL (20 mmol/L) at presentation
Type 2 diabetes features include 1:
- BMI ≥25 kg/m²
- Absence of weight loss
- Absence of ketoacidosis
- Less marked hyperglycemia at presentation
Definitive Laboratory Testing
Islet Autoantibody Testing
Measure islet autoantibodies when type 1 diabetes is clinically suspected 1:
- Primary test: Glutamic acid decarboxylase (GAD) antibodies 1
- If GAD negative: Follow with islet tyrosine phosphatase 2 (IA-2) and/or zinc transporter 8 (ZnT8) 1
- In insulin-naïve patients: Insulin autoantibodies may also be useful 1
Important caveat: In patients diagnosed at <35 years with no clinical features of type 2 diabetes, a negative antibody result does not exclude type 1 diabetes, as 5-10% of people with type 1 diabetes are antibody-negative 1
C-Peptide Measurement
C-peptide testing is indicated only in insulin-treated patients to assess endogenous insulin production 1:
- Random C-peptide >600 pmol/L (>1.8 ng/mL): Suggests preserved beta-cell function, more consistent with type 2 diabetes 1
- C-peptide <80 pmol/L (<0.24 ng/mL): Indicates severe insulin deficiency consistent with type 1 diabetes 1
- C-peptide 200-600 pmol/L (0.6-1.8 ng/mL): Usually consistent with type 1 diabetes or MODY, but may occur in insulin-treated type 2 diabetes with normal/low BMI 1
Testing requirements 1:
- Measure within 5 hours of eating with concurrent glucose
- Do not test within 2 weeks of a hyperglycemic emergency
- If result is <600 pmol/L and concurrent glucose is <70 mg/dL or patient may have been fasting, repeat the test
Critical Pitfalls to Avoid
Misdiagnosis is extremely common, occurring in approximately 40% of adults with new-onset type 1 diabetes who are incorrectly labeled as having type 2 diabetes 1. This leads to:
- Delayed insulin initiation
- Inadequate glycemic control
- Increased risk of diabetic ketoacidosis
Do not assume type 2 diabetes based solely on age 1. The traditional paradigm that type 2 diabetes occurs only in adults and type 1 only in children is no longer accurate, as both diseases occur in all age groups 1.
Ethnic minorities may present with DKA despite having type 2 diabetes 1, so ketoacidosis alone does not definitively establish type 1 diabetes.
When Classification Remains Unclear
If genetic testing for monogenic diabetes is negative and classification remains unclear, make a clinical decision about treatment 1:
- Patients with possible type 1 diabetes not treated with insulin require careful monitoring and education for rapid insulin initiation if glycemic deterioration occurs 1
- Type 2 diabetes should be strongly considered in older individuals 1
- Some patients may have features of both type 1 and type 2 diabetes, and it may be appropriate to categorize them as having features of both to facilitate access to appropriate treatment 1
The diagnosis generally becomes more obvious over time as the degree of beta-cell deficiency becomes clear 1.