What is the best test to diagnose new type 1 diabetes?

Best Test to Diagnose New Type 1 Diabetes

For diagnosing new type 1 diabetes, islet autoantibody testing is the best diagnostic test, specifically starting with glutamic acid decarboxylase (GAD) antibodies, followed by additional antibodies if needed. 1

Primary Diagnostic Approach

• Islet autoantibody testing should be the first-line test for suspected type 1 diabetes, particularly in adults with phenotypic features that overlap with type 2 diabetes (younger age at diagnosis, unintentional weight loss, ketoacidosis, or rapid progression to insulin dependence) 1
• Begin with GAD antibody testing, which should be the primary antibody measured, and if negative, follow with testing for islet tyrosine phosphatase 2 (IA-2) and/or zinc transporter 8 (ZnT8) antibodies 1
• In individuals who have not been treated with insulin, antibodies against insulin (IAA) may also be useful 1
• At clinical diagnosis, 80-90% of patients with type 1 diabetes are positive for antibodies to β-cell antigens 2

Diagnostic Algorithm

1. For patients with classic symptoms of hyperglycemia or hyperglycemic crisis:

   • Plasma blood glucose should be used rather than A1C for diagnosis of acute-onset type 1 diabetes 1
   • A random plasma glucose ≥200 mg/dL (11.1 mmol/L) with classic symptoms is diagnostic 1

2. For suspected type 1 diabetes without acute crisis:

   • Test for islet autoantibodies, starting with GAD antibodies 1
   • If GAD antibody is negative, test for IA-2 and/or ZnT8 antibodies 1
   • Presence of one or more autoantibodies confirms autoimmune etiology of diabetes 3

3. For patients <35 years of age:

   • Even with negative autoantibody results, type 1 diabetes should still be considered as 5-10% of people with type 1 diabetes do not have detectable antibodies 1

4. For patients >35 years of age with negative autoantibodies:

   • Consider C-peptide testing after >3 years duration to help differentiate between type 1 and type 2 diabetes 1

Additional Considerations

• Islet autoantibody tests should be performed only in an accredited laboratory with an established quality control program and participation in a proficiency testing program 1
• Multiple positive autoantibodies indicate a higher risk of progression to insulin dependence 1, 3
• 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 1

Staging of Type 1 Diabetes

• Stage 1: Multiple autoantibodies with normoglycemia (presymptomatic) 1
• Stage 2: Autoantibodies with dysglycemia (presymptomatic) 1
• Stage 3: Clinical diabetes with overt hyperglycemia (symptomatic) - this is when most patients are diagnosed 1

Common Pitfalls to Avoid

• Do not rely solely on A1C for diagnosis in conditions with altered relationship between A1C and glycemia (hemoglobinopathies, pregnancy, glucose-6-phosphate dehydrogenase deficiency, HIV, hemodialysis, recent blood loss or transfusion) 1
• Avoid using point-of-care A1C assays for diagnosis unless they are FDA-cleared specifically for diagnostic purposes 1
• Remember that 5-10% of adult-onset type 1 diabetes may be autoantibody negative, so clinical judgment remains important 1
• Do not test C-peptide within 2 weeks of a hyperglycemic emergency as results may be misleading 1

By following this diagnostic approach, clinicians can accurately diagnose type 1 diabetes and distinguish it from other forms of diabetes, ensuring appropriate treatment and management strategies.