What labs are used to confirm type 1 diabetes?

Laboratory Tests to Confirm Type 1 Diabetes

To confirm type 1 diabetes, measurement of pancreatic autoantibodies (anti-GAD, anti-IA2, anti-insulin, anti-ZnT8) is essential, along with standard glycemic tests and C-peptide assessment. 1

Standard Glycemic Tests for Initial Diagnosis

• Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L), with fasting defined as no caloric intake for at least 8 hours 2
• 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test (OGTT) using 75g of anhydrous glucose 2
• Random plasma glucose ≥200 mg/dL (11.1 mmol/L) in patients with classic symptoms of hyperglycemia or hyperglycemic crisis 2, 1
• HbA1c ≥6.5% (48 mmol/mol) performed in a laboratory using a method certified by the National Glycohemoglobin Standardization Program (NGSP) 2, 3

Specific Tests to Confirm Type 1 Diabetes

• Pancreatic autoantibody panel - essential for confirming the autoimmune nature of type 1 diabetes 1:

  • Glutamic acid decarboxylase autoantibodies (GAD65)
  • Insulin autoantibodies (IAA)
  • Tyrosine phosphatase autoantibodies (IA-2 and IA-2β)
  • Zinc transporter 8 autoantibodies (ZnT8)
  • Islet cell autoantibodies (ICA)

• C-peptide levels - typically low or undetectable in type 1 diabetes, indicating diminished beta-cell function 1, 2

• Ketone testing - blood or urine ketones should be measured, as approximately one-third of type 1 diabetes patients present with diabetic ketoacidosis (DKA) at diagnosis 1

Diagnostic Algorithm for Type 1 Diabetes

1. Initial glycemic assessment: Perform standard glycemic tests (FPG, random glucose, or HbA1c) 2, 3
2. Confirmation: In the absence of unequivocal hyperglycemia, diagnosis requires two abnormal test results obtained at the same time (e.g., A1C and FPG) or at two different time points 2
3. Type 1 diabetes-specific testing: Measure pancreatic autoantibodies and C-peptide levels 1, 2
4. Ketone assessment: Test for ketones in blood or urine 1

Special Considerations

• For patients with conditions affecting red blood cell turnover (sickle cell disease, pregnancy, hemodialysis, recent blood loss, transfusion, or erythropoietin therapy), only plasma glucose criteria should be used for diagnosis 2, 1
• When there is discordance between measured A1C levels and plasma glucose levels, consider possible interference in the A1C assay due to hemoglobin variants 2, 3
• In overweight or obese adolescents where distinguishing between type 1 and type 2 diabetes may be challenging, measurement of islet autoantibodies and C-peptide concentrations is particularly important 2
• Point-of-care A1C testing for diabetes diagnosis should be restricted to FDA-approved devices at CLIA-certified laboratories with trained personnel 2

Common Pitfalls and Caveats

• HbA1c testing alone is not recommended for diagnosing acute-onset type 1 diabetes due to limitations in conditions affecting red blood cell turnover 1
• Glucose concentrations can be falsely low if samples are not processed promptly or stored properly prior to analysis due to glycolysis 2
• Stress hyperglycemia, particularly in children with acute illness, can lead to elevated glucose levels that do not necessarily indicate diabetes 2
• Monogenic diabetes (approximately 1.2-4% of pediatric diabetes) is frequently misdiagnosed as type 1 diabetes and should be considered in antibody-negative patients 2
• There is limited agreement between different diagnostic tests (FPG, OGTT, and HbA1c), with concordance as low as 34% between OGTT and HbA1c for diabetes diagnosis 4