Diagnosing Type 1 Diabetes

Primary Diagnostic Approach

The American Diabetes Association recommends islet autoantibody testing as the first-line test for suspected type 1 diabetes, particularly in adults with phenotypic features that overlap with type 2 diabetes, starting with glutamic acid decarboxylase (GAD) antibodies, followed by additional antibodies if needed 1, 2, 3, 4
The primary antibody measured should be GAD, and if negative, testing for islet tyrosine phosphatase 2 (IA-2) and/or zinc transporter 8 (ZnT8) antibodies should follow 5, 6
In individuals who have not been treated with insulin, antibodies against insulin (IAA) may also be useful 5, 6

For patients with classic symptoms of hyperglycemia or hyperglycemic crisis, plasma blood glucose should be used rather than A1C for diagnosis, with a random plasma glucose ≥200 mg/dL (11.1 mmol/L) being diagnostic 7, 8
For suspected type 1 diabetes without acute crisis, testing for islet autoantibodies, starting with GAD antibodies, is recommended 1, 5

Islet autoantibody tests should be performed only in an accredited laboratory with an established quality control program and participation in a proficiency testing program 9
Multiple positive autoantibodies indicate a higher risk of progression to insulin dependence 4
C-peptide testing is particularly useful in insulin-treated patients to assess residual β-cell function, but should not be performed within 2 weeks of a hyperglycemic emergency 5, 6

Stage 1: Multiple autoantibodies with normoglycemia (presymptomatic) can be identified through islet autoantibody testing 3, 4
Stage 2: Autoantibodies with dysglycemia (presymptomatic) can be identified through islet autoantibody testing 3, 4
Stage 3: Clinical diabetes with overt hyperglycemia (symptomatic) is typically when most patients are diagnosed 3, 4

The American Diabetes Association advises against relying solely on A1C for diagnosis in conditions with altered relationship between A1C and glycemia 8
Point-of-care A1C assays should not be used for diagnosis unless they are FDA-cleared specifically for diagnostic purposes 8
Clinical judgment remains important, as 5-10% of adult-onset type 1 diabetes may be autoantibody negative 5, 6
C-peptide testing should not be performed within 2 weeks of a hyperglycemic emergency, as results may be misleading 5, 6