What lab tests are used to diagnose type 1 diabetes?

Laboratory Tests for Type 1 Diabetes

In patients with classic symptoms of hyperglycemia, a random plasma glucose ≥200 mg/dL (11.1 mmol/L) is sufficient to diagnose diabetes immediately, and plasma glucose—not HbA1c—should be used for acute-onset type 1 diabetes. 1, 2

Diagnostic Tests for Symptomatic Patients

When a patient presents with classic symptoms (polyuria, polydipsia, weight loss, polyphagia, fatigue, blurred vision), the following tests confirm diabetes 1:

• Random plasma glucose ≥200 mg/dL (11.1 mmol/L) requires no repeat testing if symptoms are present 1, 3
• Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L) with no caloric intake for at least 8 hours 1, 3
• 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during oral glucose tolerance test using 75g glucose (or 1.75 g/kg up to 75g maximum in children) 1, 3
• HbA1c ≥6.5% (48 mmol/mol) using NGSP-certified laboratory method 1, 3

Critical caveat: Plasma glucose samples must be spun and separated immediately after collection to prevent falsely low results from glycolysis 1, 3. Delays in diagnosis must be avoided as the metabolic state can deteriorate rapidly in children 1, 4.

Confirmation Testing in Asymptomatic Patients

For asymptomatic individuals (such as those screened due to family history), confirmation requires 1:

• Two abnormal results from the same sample (e.g., both FPG ≥126 mg/dL and HbA1c ≥6.5%) 1, 3
• OR repeat testing on a separate day using the same test 1
• If two different tests are discordant, repeat the test above the diagnostic threshold 1

Tests to Confirm Type 1 (vs Type 2) Diabetes

Once diabetes is diagnosed, these tests distinguish type 1 from other forms 1, 3:

Autoantibody Panel (Primary Confirmatory Tests)

Measure the following islet autoantibodies in standardized, accredited laboratories 1, 3:

• Glutamic acid decarboxylase (GAD65) - test first 4
• Insulin autoantibodies (IAA) 1, 3
• Tyrosine phosphatase (IA-2 and IA-2β) - test if GAD negative 1, 3, 4
• Zinc transporter 8 (ZnT8) - test if GAD negative 1, 3, 4
• Islet cell autoantibodies (ICA) 3

The presence of one or more autoantibodies defines type 1 diabetes, though multiple autoantibodies indicate higher risk of progression to insulin dependence 1, 4. Note that 5-10% of adult-onset type 1 diabetes may be autoantibody-negative 4.

C-Peptide Testing

• Low or undetectable C-peptide levels indicate diminished beta-cell function characteristic of type 1 diabetes 3, 2
• Do not perform within 2 weeks of diabetic ketoacidosis as results may be misleading 4
• Particularly useful in overweight/obese adolescents to distinguish type 1 from type 2 diabetes 1, 3

Ketone Testing

• Test for ketones in blood or urine when type 1 diabetes is suspected, as approximately one-third present with diabetic ketoacidosis 2

When NOT to Use HbA1c

HbA1c should not be used alone for diagnosing acute-onset type 1 diabetes 1, 2. Use only plasma glucose criteria in these conditions 3, 2:

• Sickle cell disease or other hemoglobinopathies 3
• Pregnancy 3
• Hemodialysis 3
• Recent blood loss or transfusion 3
• Erythropoietin therapy 3
• Any condition affecting red blood cell turnover 3, 2

Point-of-care HbA1c assays should not be used for diagnosis unless specifically FDA-cleared for this purpose 4.

Screening for Type 1 Diabetes Risk

Autoantibody screening in asymptomatic individuals is recommended only in 1:

• Research study settings 1
• First-degree relatives of someone with type 1 diabetes 1

Persistence of two or more autoantibodies predicts clinical diabetes and defines presymptomatic stages 1:

• Stage 1: ≥2 autoantibodies + normoglycemia (44% develop diabetes within 5 years) 1
• Stage 2: ≥2 autoantibodies + dysglycemia (75% develop diabetes within 5 years) 1
• Stage 3: Symptomatic diabetes 1

Critical Pitfalls to Avoid

• Do not delay diagnosis in symptomatic children—metabolic deterioration can be rapid 1, 4
• Do not mistake stress hyperglycemia for diabetes in young children with acute illness, especially without classic symptoms 1, 4
• Do not use glucose meters or urine tests alone—confirm with venous plasma glucose on clinical chemistry analyzer 1
• Consider monogenic diabetes (MODY, neonatal diabetes) in antibody-negative youth, as it's frequently misdiagnosed as type 1 diabetes 1, 4
• Ensure proper sample handling—glucose samples left at room temperature without prompt centrifugation yield falsely low results 1