What blood work is needed to rule out Type 1 Diabetes?

Blood Work to Rule Out Type 1 Diabetes

To rule out Type 1 diabetes, blood work should include fasting plasma glucose (FPG), 2-hour plasma glucose during oral glucose tolerance test (OGTT), A1C, and islet autoantibody testing (GAD65, IA-2, ZnT8, and insulin autoantibodies).

Diagnostic Blood Tests for Glycemic Status

Primary Glycemic Tests

• Fasting Plasma Glucose (FPG): ≥126 mg/dL (7.0 mmol/L) after at least 8 hours of fasting 1
• 2-hour Plasma Glucose (2-h PG): ≥200 mg/dL (11.1 mmol/L) during 75g OGTT 1
• A1C: ≥6.5% (48 mmol/mol) using NGSP-certified method 1
• Random Plasma Glucose: ≥200 mg/dL (11.1 mmol/L) with classic symptoms 1

Confirmation Requirements

• Unless there is unequivocal hyperglycemia with classic symptoms, diagnosis requires two abnormal test results from the same sample or in two separate test samples 1
• If two different tests (such as A1C and FPG) are both above diagnostic thresholds, this confirms the diagnosis 1

Autoantibody Testing for Type 1 Diabetes

Essential Autoantibody Panel

• Glutamic Acid Decarboxylase (GAD65) autoantibodies 2
• Islet Antigen 2 (IA-2) autoantibodies 2
• Zinc Transporter 8 (ZnT8) autoantibodies 2
• Insulin autoantibodies (IAA) - only if not already on insulin therapy 2

Interpretation of Autoantibody Results

• The presence of one or more islet autoantibodies confirms the autoimmune etiology of Type 1 diabetes 2
• The presence of two or more autoantibodies is highly predictive of progression to clinical Type 1 diabetes 1, 2
• Note that 5-10% of Type 1 diabetes patients may be antibody-negative, particularly in individuals of African or Asian ancestry 2

Additional Testing to Differentiate Type 1 from Type 2 Diabetes

C-peptide Testing

• Random C-peptide with concurrent glucose: Helps assess endogenous insulin production 2
  • 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

Special Considerations

• For patients with hemoglobinopathies or conditions with altered red blood cell turnover (sickle cell disease, pregnancy, hemodialysis, recent blood loss/transfusion, erythropoietin therapy), only plasma glucose criteria should be used 1, 2
• Pre-analytic variability can be avoided by spinning and separating samples for plasma glucose immediately after they are drawn 1

Important Caveats

• Marked discordance between A1C and plasma glucose levels should raise suspicion of A1C assay interference due to hemoglobin variants 1
• Obesity does not rule out Type 1 diabetes, as it can occur in individuals with obesity 2
• Incidental hyperglycemia may represent "stress hyperglycemia" rather than new-onset diabetes, especially in young children with acute illness 2
• Testing for diabetic ketoacidosis (DKA) is essential in the diagnostic workup, as approximately one-third of children with Type 1 diabetes present with DKA 2

By following this comprehensive testing approach, clinicians can effectively rule out Type 1 diabetes or confirm its diagnosis, enabling appropriate and timely treatment.