What blood tests are used to diagnose type 1 diabetes?

Blood Tests for Diagnosing Type 1 Diabetes

Plasma glucose tests, rather than HbA1c, should be used as the primary diagnostic tests for acute onset of type 1 diabetes in individuals with symptoms of hyperglycemia. 1

Primary Diagnostic Tests

• Fasting Plasma Glucose (FPG): A value ≥126 mg/dL (7.0 mmol/L) after at least 8 hours of fasting is diagnostic for diabetes 2, 1
• 2-hour Plasma Glucose: A value ≥200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test (OGTT) using 75g of anhydrous glucose is diagnostic 2, 1
• Random Plasma Glucose: A value ≥200 mg/dL (11.1 mmol/L) in patients with classic symptoms of hyperglycemia (polyuria, polydipsia, unexplained weight loss) or hyperglycemic crisis is diagnostic 2, 1

Autoantibody Testing

• Islet Autoantibodies: Testing for autoantibodies is recommended to confirm the autoimmune nature of type 1 diabetes, especially in adults with overlapping phenotypic risk factors 2, 1
• Specific Autoantibodies to Test:
  • Islet cell autoantibodies (ICA) 1
  • Glutamic acid decarboxylase autoantibodies (GAD65) 2, 1
  • Insulin autoantibodies 2, 1
  • Tyrosine phosphatase autoantibodies (IA-2 and IA-2β) 2, 1
  • Zinc transporter 8 autoantibodies (ZnT8) 2, 1
• The presence of one or more of these autoimmune markers defines type 1 diabetes 2
• Multiple positive autoantibodies strongly predict clinical diabetes development 2

Beta-Cell Function Assessment

• C-peptide: Measuring C-peptide levels is recommended to assess beta-cell function; low or undetectable levels are characteristic of type 1 diabetes 1

Confirmation Requirements

• Unless there is a clear clinical diagnosis (e.g., patient in hyperglycemic crisis or with classic symptoms plus random glucose ≥200 mg/dL), diagnosis requires two abnormal test results 2
• Confirmation can be achieved through:
  • Two abnormal results from the same sample 2
  • Two abnormal results from separate test samples 2
  • Two different tests (such as FPG and A1C) both above diagnostic thresholds 2

Special Considerations

• Ketone Testing: Blood or urine ketone testing should be performed when type 1 diabetes is suspected, as approximately one-third of patients present with diabetic ketoacidosis (DKA) 1
• Timing of Tests: Morning FPG values tend to be higher than afternoon values (5.41 vs. 5.12 mmol/L), which may affect diagnosis if testing is done in the afternoon 3
• Sample Handling: For plasma glucose tests, samples should be spun and separated immediately after drawing to prevent preanalytic variability 2

Limitations of HbA1c Testing

• HbA1c should not be used as the sole diagnostic test for acute onset type 1 diabetes 1
• HbA1c testing is unreliable in conditions affecting red blood cell turnover, such as:
  • Hemoglobinopathies 2
  • Pregnancy (second and third trimesters) 2
  • Glucose-6-phosphate dehydrogenase deficiency 2
  • Hemodialysis 2
  • Recent blood loss or transfusion 2
  • Erythropoietin therapy 2

Screening for Type 1 Diabetes Risk

• Screening with autoantibody panels is currently recommended only in research settings or for first-degree family members of individuals with type 1 diabetes 2, 1
• Persistence of two or more autoantibodies is a significant risk factor for developing clinical diabetes 2, 1