What are the tests used to diagnose type 1 diabetes?

Diagnostic Tests for Type 1 Diabetes

The diagnosis of type 1 diabetes requires standard glycemic criteria testing (A1C ≥6.5%, fasting plasma glucose ≥126 mg/dL, 2-hour plasma glucose ≥200 mg/dL during OGTT, or random plasma glucose ≥200 mg/dL with symptoms), plus testing for islet autoantibodies to confirm the autoimmune etiology. 1

Primary Diagnostic Criteria

Type 1 diabetes is diagnosed using the same glycemic criteria as other types of diabetes, but with additional testing to confirm autoimmune etiology:

Glycemic Testing

• A1C ≥6.5% (48 mmol/mol) - Test must be performed using NGSP-certified method standardized to DCCT assay 2
• Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L) - Fasting defined as no caloric intake for at least 8 hours 2
• 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during 75g OGTT 2
• Random plasma glucose ≥200 mg/dL (11.1 mmol/L) with classic symptoms of hyperglycemia or hyperglycemic crisis 2

Unless there is unequivocal hyperglycemia with acute metabolic decompensation, a second confirmatory test is required, using either the same test or a different test 2.

Autoimmunity Testing

For type 1 diabetes specifically, testing for islet autoantibodies is crucial:

• Glutamic acid decarboxylase (GAD) - Primary antibody to test 1
• Islet antigen 2 (IA-2) 1
• Zinc transporter 8 (ZnT8) 1
• Insulin autoantibodies (only if patient is not already on insulin therapy) 1

The presence of one or more of these autoantibodies confirms the autoimmune etiology of type 1 diabetes 2.

C-peptide Testing

C-peptide measurement helps assess endogenous insulin production:

• Random C-peptide with concurrent glucose (within 5 hours of eating) 1
• C-peptide values <200 pmol/L (<0.6 ng/mL) suggest type 1 diabetes 1
• C-peptide values >600 pmol/L (>1.8 ng/mL) suggest type 2 diabetes 1
• Values between 200-600 pmol/L indicate indeterminate classification 1

C-peptide testing is particularly useful after >3 years of diabetes duration if diagnosis remains unclear 1.

Important Considerations and Pitfalls

A1C Limitations

• A1C may be unreliable in conditions with altered red blood cell turnover:
  • Hemoglobinopathies (sickle cell trait/disease)
  • Pregnancy (second and third trimesters)
  • Hemodialysis
  • Recent blood loss or transfusion
  • Erythropoietin therapy
  • Glucose-6-phosphate dehydrogenase deficiency
  • HIV infection 2

In these cases, only plasma glucose criteria should be used for diagnosis 2.

Discordance Between Tests

• Marked discordance between A1C and plasma glucose levels should raise suspicion of A1C assay interference 2
• Different tests do not necessarily detect diabetes in the same individuals 2
• When results from two different tests are discordant, the test above the diagnostic threshold should be repeated 2

Antibody Testing Considerations

• 5-10% of type 1 diabetes patients may be antibody-negative, particularly in individuals of African or Asian ancestry 1
• Testing multiple antibodies increases diagnostic sensitivity 1

Clinical Presentation

• Type 1 diabetes often presents with acute symptoms (polyuria, polydipsia, weight loss)
• Approximately one-third of children present with diabetic ketoacidosis (DKA) 1
• Adult-onset type 1 diabetes may have a more gradual progression than childhood-onset 2

Diagnostic Algorithm

1. Initial glycemic assessment using one or more of:

   • A1C (if no conditions affecting reliability)
   • Fasting plasma glucose
   • 2-hour plasma glucose during OGTT
   • Random plasma glucose (if symptoms present)

2. Confirm diagnosis with a second test if initial test is positive (unless unequivocal hyperglycemia with symptoms)

3. Test for autoantibodies to confirm type 1 diabetes:

   • Start with GAD antibodies
   • Add IA-2, ZnT8, and insulin antibodies (if not on insulin)

4. Measure C-peptide to assess endogenous insulin production if diagnosis remains unclear

5. Screen for associated autoimmune conditions commonly seen with type 1 diabetes:

   • Thyroid disorders (Hashimoto's, Graves')
   • Celiac disease

This comprehensive approach ensures accurate diagnosis of type 1 diabetes, which is critical for appropriate treatment and management to reduce morbidity and mortality.