What are the diagnostic tests for type 1 diabetes?

Diagnostic Tests for Type 1 Diabetes

The diagnosis of type 1 diabetes requires both glycemic testing and autoantibody testing to confirm autoimmune etiology, with the primary diagnostic criteria being fasting plasma glucose ≥126 mg/dL, 2-hour plasma glucose ≥200 mg/dL during OGTT, A1C ≥6.5%, or random plasma glucose ≥200 mg/dL with classic symptoms, along with positive islet autoantibodies. 1

Glycemic Testing Criteria

Type 1 diabetes can be diagnosed using any of the following glycemic criteria:

• Fasting Plasma Glucose (FPG): ≥126 mg/dL (7.0 mmol/L) after no caloric intake for at least 8 hours 2, 1
• 2-hour Plasma Glucose: ≥200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test (OGTT) using a glucose load containing 75g of anhydrous glucose 2, 1
• A1C: ≥6.5% (48 mmol/mol) using a method that is NGSP certified and standardized to the DCCT assay 2, 1
• Random Plasma Glucose: ≥200 mg/dL (11.1 mmol/L) in a patient with classic symptoms of hyperglycemia (polyuria, polydipsia, weight loss) or hyperglycemic crisis 2, 1

Confirmation Requirements

• In the absence of unequivocal hyperglycemia with acute symptoms or hyperglycemic crisis, diagnosis requires confirmation with a repeat test 2, 1
• Confirmation can be with the same test on a different day or a different test 1
• For patients with classic symptoms and random plasma glucose ≥200 mg/dL, no repeat testing is required 2
• If two different tests (such as A1C and FPG) are both above diagnostic thresholds, this also confirms the diagnosis 2

Autoantibody Testing

To confirm the autoimmune etiology of type 1 diabetes, testing for one or more of the following autoantibodies is essential:

• Glutamic acid decarboxylase (GAD65) autoantibodies 2, 1
• Islet antigen 2 (IA-2) autoantibodies 1
• Zinc transporter 8 (ZnT8) autoantibodies 1
• Insulin autoantibodies (if not already on insulin therapy) 1

The presence of two or more islet autoantibodies indicates stage 1 of type 1 diabetes in individuals with normoglycemia, while the presence of autoantibodies with dysglycemia indicates stage 2 2.

Additional Diagnostic Tests

• C-peptide levels: Helps assess endogenous insulin production 1

  • Values <200 pmol/L (<0.6 ng/mL) suggest type 1 diabetes
  • Values >600 pmol/L (>1.8 ng/mL) suggest type 2 diabetes
  • Values between 200-600 pmol/L indicate indeterminate classification

• Testing for other autoimmune disorders: Screening for commonly associated conditions such as Hashimoto thyroiditis, Graves disease, and celiac disease is recommended 1

Distinguishing Type 1 from Type 2 Diabetes

Distinguishing between type 1 and type 2 diabetes can be challenging, especially in overweight or obese adolescents. In such cases:

• Detailed family history 2
• Measurement of islet autoantibodies 2
• Plasma or urinary C-peptide concentrations 2, 1

Screening for Type 1 Diabetes in Asymptomatic Individuals

• Screening with a panel of autoantibodies is currently recommended only in research settings or as an option for first-degree family members of individuals with type 1 diabetes 2
• Persistence of autoantibodies is a risk factor for clinical diabetes and may serve as an indication for intervention in clinical trials 2

Common Pitfalls and Caveats

• Incidental hyperglycemia: The incidental discovery of hyperglycemia without classic symptoms, especially in young children with acute illness, may represent "stress hyperglycemia" rather than new-onset diabetes 2

• Hemoglobinopathies: For patients with hemoglobinopathies or abnormal red cell turnover, glucose criteria must be used exclusively instead of A1C 1

• Point-of-care testing: Glucose meters and urine ketone tests are useful for screening but diagnosis must be confirmed by measurement of venous plasma glucose in a clinical laboratory 2, 1

• Antibody-negative type 1 diabetes: 5-10% of type 1 diabetes patients may be antibody-negative, particularly in individuals of African or Asian ancestry 1

• Monogenic diabetes: This form is frequently misdiagnosed as type 1 diabetes and inappropriately treated with insulin. Consider this possibility in antibody-negative youth with diabetes, particularly in children diagnosed in the first 6 months of life 2

• Pre-analytic variability: To avoid false negatives, samples for plasma glucose should be spun and separated immediately after they are drawn 2