What are the steps for testing and diagnosing type 1 diabetes?

Testing and Diagnosis of Type 1 Diabetes

The diagnosis of type 1 diabetes should be made using plasma blood glucose rather than A1C in individuals with symptoms of hyperglycemia, with a random plasma glucose ≥200 mg/dL (11.1 mmol/L) being diagnostic when classic symptoms are present. 1, 2

Initial Diagnostic Approach

For Patients with Classic Symptoms

• In patients presenting with classic symptoms of hyperglycemia or hyperglycemic crisis, measurement of plasma glucose is sufficient to diagnose diabetes (symptoms plus random plasma glucose ≥200 mg/dL [11.1 mmol/L]) 1
• Samples for plasma glucose should be spun and separated immediately after they are drawn to prevent preanalytic variability 1
• Approximately one-third of patients with type 1 diabetes present with life-threatening diabetic ketoacidosis (DKA) 1

For Patients Without Acute Crisis

• Testing for islet autoantibodies is recommended, starting with glutamic acid decarboxylase (GAD) antibodies 2
• If GAD antibodies are negative, testing should proceed to islet tyrosine phosphatase 2 (IA-2) and/or zinc transporter 8 (ZnT8) antibodies 2
• In individuals not yet treated with insulin, insulin autoantibodies (IAA) may also be useful 2
• Type 1 diabetes is defined by the presence of one or more autoimmune markers 1

Confirmation of Diagnosis

• If the initial diagnostic test is not conclusive or if the patient does not present with classic symptoms, diagnosis requires two abnormal test results 1
• These can be from the same sample or from two separate test samples 1
• If using two separate samples, the second test should be performed without delay 1
• If two different tests (such as A1C and FPG) are both above diagnostic thresholds, this confirms the diagnosis 1

C-peptide Testing

• C-peptide testing is particularly useful in insulin-treated patients to assess residual β-cell function 2
• Should not be performed within 2 weeks of a hyperglycemic emergency as results may be misleading 2
• Very low C-peptide levels (<80 pmol/L [<0.24 ng/mL]) are indicative of type 1 diabetes 1

Autoantibody Testing Considerations

• Islet autoantibody tests should be performed only in accredited laboratories with established quality control programs 2
• Multiple positive autoantibodies indicate a higher risk of progression to insulin dependence 2
• In those diagnosed at <35 years of age who have no clinical features of type 2 diabetes or monogenic diabetes, a negative antibody result does not change the diagnosis of type 1 diabetes, since 5–10% of people with type 1 diabetes do not have antibodies 1, 2

Staging of Type 1 Diabetes

• Stage 1: Multiple autoantibodies with normoglycemia (presymptomatic) 2
• Stage 2: Autoantibodies with dysglycemia (presymptomatic) 2
• Stage 3: Clinical diabetes with overt hyperglycemia (symptomatic) - this is when most patients are diagnosed 2

Screening for Type 1 Diabetes Risk

• Screening for type 1 diabetes risk with a panel of islet autoantibodies is currently recommended in research settings or can be offered as an option for first-degree family members of a person with type 1 diabetes 1
• Persistence of two or more autoantibodies predicts clinical diabetes and may serve as an indication for intervention in the setting of a clinical trial 1

Additional Testing for Associated Conditions

• Screen for additional autoimmune conditions soon after diagnosis of type 1 diabetes 1
• Consider testing for antithyroid peroxidase and antithyroglobulin antibodies soon after diagnosis 1
• Screen for celiac disease by measuring IgA tissue transglutaminase (tTG) antibodies, with documentation of normal total serum IgA levels 1

Common Pitfalls to Avoid

• Do not rely solely on A1C for diagnosis in conditions with altered relationship between A1C and glycemia 2
• Point-of-care A1C assays should not be used for diagnosis unless FDA-cleared specifically for diagnostic purposes 2
• Thyroid function tests may be misleading if performed at the time of diagnosis due to effects of previous hyperglycemia, ketosis, or weight loss 1
• C-peptide testing should not be performed within 2 weeks of a hyperglycemic emergency 2
• Samples for plasma glucose must be spun and separated immediately to prevent false negative results 1