What lab tests are used to diagnose type 1 diabetes?

Laboratory Tests for Type 1 Diabetes Diagnosis

For diagnosing type 1 diabetes, use plasma glucose testing (fasting ≥126 mg/dL, random ≥200 mg/dL with symptoms, or 2-hour OGTT ≥200 mg/dL) as the primary diagnostic test, then confirm the autoimmune etiology with pancreatic autoantibody testing (GAD65, IA-2, insulin autoantibodies, ZnT8) and assess beta-cell function with C-peptide levels. 1, 2

Initial Glycemic Testing

Plasma glucose is preferred over HbA1c for acute-onset type 1 diabetes because patients often present with rapid symptom onset where HbA1c may not yet reflect the severity of hyperglycemia. 3, 2

The diagnostic thresholds are: 1, 4

• Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L) after at least 8 hours without caloric intake
• Random plasma glucose ≥200 mg/dL (11.1 mmol/L) in patients with classic hyperglycemia symptoms (polyuria, polydipsia, weight loss)
• 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during 75g oral glucose tolerance test
• HbA1c ≥6.5% (48 mmol/mol) using NGSP-certified laboratory method (though not preferred for acute diagnosis)

Confirm diagnosis with two abnormal test results either from the same sample using different tests (e.g., FPG and HbA1c both elevated) or by repeating the same test on a separate day. 1, 4 The exception is when random glucose ≥200 mg/dL occurs with unequivocal hyperglycemic symptoms—this single result is diagnostic. 1

Autoantibody Testing to Confirm Type 1 Etiology

After establishing hyperglycemia, measure pancreatic autoantibodies to confirm the autoimmune nature of type 1 diabetes. 1, 2 This distinguishes type 1 from type 2 diabetes and other forms.

Test for the following autoantibodies: 3, 1, 2

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

The presence of one or more autoantibodies defines type 1 diabetes. 3, 2 However, standardized islet autoantibody tests should be used, particularly when there is phenotypic overlap between type 1 and type 2 diabetes in adults. 3

C-Peptide Testing for Beta-Cell Function

Measure C-peptide levels to assess residual beta-cell function—low or undetectable C-peptide confirms significant beta-cell destruction characteristic of type 1 diabetes. 1, 2 This distinguishes type 1 diabetes (low C-peptide) from type 2 diabetes (normal or elevated C-peptide). 4

Ketone Testing at Presentation

Approximately one-third of type 1 diabetes patients present with diabetic ketoacidosis (DKA). 3, 2 When type 1 diabetes is suspected:

• Measure beta-hydroxybutyrate in blood for diagnosis and monitoring of DKA—this is superior to urine ketone testing. 3
• Blood ketone testing using the nitroprusside reaction should not be used for DKA monitoring. 3
• Individuals prone to ketosis should measure ketones when experiencing unexplained hyperglycemia or symptoms like abdominal pain and nausea. 3

Critical Sample Handling Requirements

Blood samples for glucose testing must be processed immediately to prevent falsely low results: 3

• Use tubes containing granulated citrate buffer (rapidly effective glycolytic inhibitor)
• If immediate processing is impossible, place samples in ice-water slurry immediately
• Centrifuge within 15-30 minutes to separate plasma
• Do not rely on sodium fluoride alone—it inhibits enolase but does not prevent glycolysis rapidly enough 3

Common Pitfalls and Special Considerations

Do not use HbA1c alone for diagnosing acute-onset type 1 diabetes in patients with symptoms, as conditions affecting red blood cell turnover (pregnancy, recent blood loss, hemolysis, sickle cell disease) can interfere with results. 1, 2 Use plasma glucose criteria instead. 3, 4

Consider monogenic diabetes in antibody-negative patients, as it is frequently misdiagnosed as type 1 diabetes. 1 Genetic testing for neonatal diabetes and maturity-onset diabetes of the young (MODY) can provide valuable treatment information in selected cases. 3

In children with acute illness, consider stress hyperglycemia as a potential cause of elevated glucose that does not necessarily indicate diabetes. 1 Confirm with repeat testing after illness resolution.

Routine genetic testing (HLA typing, single nucleotide polymorphisms) has no value for diagnosis or management of established type 1 diabetes. 3 Reserve genetic marker testing for research settings or when diabetes type cannot be clearly classified. 3

Screening First-Degree Relatives

Screening for type 1 diabetes risk with autoantibody panels is recommended only in research trials or for first-degree relatives of individuals with type 1 diabetes. 3, 2 Persistence of two or more autoantibodies predicts clinical diabetes and allows staging: 3

• Stage 1: Two or more autoantibodies, normoglycemia, no symptoms
• Stage 2: Two or more autoantibodies, dysglycemia, no symptoms
• Stage 3: Two or more autoantibodies, diabetes with symptoms