What are the diagnostic tests and management options for a patient with symptoms suggestive of type 1 diabetes, such as polydipsia, polyuria, weight loss, and blurred vision?

How to Check for Type 1 Diabetes

In patients with classic symptoms of hyperglycemia (polyuria, polydipsia, weight loss, blurred vision), measure a random plasma glucose—if ≥200 mg/dL (11.1 mmol/L), this confirms diabetes immediately and you should start insulin therapy without delay. 1

Diagnostic Approach Based on Clinical Presentation

For Symptomatic Patients (Acute Presentation)

Immediate blood glucose testing is sufficient for diagnosis when classic symptoms are present. The metabolic state can deteriorate rapidly in untreated type 1 diabetes, so delays in diagnosis and treatment must be avoided. 1

• Random plasma glucose ≥200 mg/dL (11.1 mmol/L) plus symptoms of hyperglycemia confirms diabetes 1
• Classic symptoms include: polyuria, polydipsia, weight loss, polyphagia, fatigue, and blurred vision from lens swelling 1
• Children often present with these hallmark symptoms, and approximately half present with diabetic ketoacidosis (DKA) 1

For Patients Without Clear Symptoms or Ambiguous Presentation

When symptoms are absent or the diagnosis is uncertain, confirm diabetes with two abnormal test results (either the same test repeated or two different tests): 1

Diagnostic thresholds (any of the following):

• Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L) on two occasions (fasting = no caloric intake for ≥8 hours) 1, 2
• 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during 75g oral glucose tolerance test (OGTT) on two occasions 1, 2
• HbA1c ≥6.5% (48 mmol/mol) on two occasions, using NGSP-certified laboratory method 1, 2

Critical exception: A single abnormal test confirms diabetes if accompanied by: 1, 2

• Classic symptoms of hyperglycemia, OR
• HbA1c ≥6.5%, OR
• Diabetic retinopathy

Distinguishing Type 1 from Type 2 Diabetes

After confirming diabetes, test for islet autoantibodies to distinguish type 1 from type 2 diabetes, especially in adults where the presentation may overlap. 1, 2, 3

Autoantibody Testing Algorithm

Start with glutamic acid decarboxylase (GAD) antibodies as the primary test: 2, 3

• If GAD positive → confirms type 1 diabetes 2, 3
• If GAD negative → test for islet tyrosine phosphatase 2 (IA-2) and/or zinc transporter 8 (ZnT8) antibodies 2, 3
• In insulin-naïve patients, insulin autoantibodies (IAA) may also be useful 3
• Presence of ≥2 autoantibodies strongly confirms type 1 diabetes and indicates higher risk of progression to insulin dependence 1, 2, 3

Important caveat: 5-10% of adult-onset type 1 diabetes may be autoantibody negative, so clinical judgment remains essential. 1, 3

Additional Testing for Insulin-Treated Patients

C-peptide testing assesses residual β-cell function in patients already on insulin: 2, 3

• Low or undetectable C-peptide supports type 1 diabetes
• Do NOT perform within 2 weeks of a hyperglycemic emergency (DKA or hyperosmolar state), as results will be misleading 2, 3

Staging of Type 1 Diabetes

Type 1 diabetes progresses through three distinct stages, which can be identified through autoantibody testing: 1, 2

• Stage 1: ≥2 autoantibodies + normoglycemia (FPG <100 mg/dL, 2-h PG <140 mg/dL) + presymptomatic 1, 2
• Stage 2: ≥2 autoantibodies + dysglycemia (FPG 100-125 mg/dL or 2-h PG 140-199 mg/dL or HbA1c 5.7-6.4%) + presymptomatic 1, 2
• Stage 3: Symptomatic disease with overt hyperglycemia meeting diabetes criteria 1, 2

Laboratory Quality Requirements

All autoantibody tests must be performed in an accredited laboratory with established quality control and participation in proficiency testing programs. 2, 3

HbA1c must be measured using an NGSP-certified method standardized to the DCCT assay. 1

Point-of-care HbA1c assays should NOT be used for diagnosis unless FDA-cleared specifically for diagnostic purposes. 1, 3

Critical Pitfalls to Avoid

• Do not use HbA1c for diagnosis in conditions with altered erythrocyte turnover: sickle cell disease, pregnancy (second/third trimesters), hemodialysis, recent blood loss/transfusion, erythropoietin therapy, hemoglobinopathies, or anemia—use only plasma glucose criteria in these situations 1, 3
• Do not delay treatment once diabetes is confirmed in symptomatic patients—the metabolic state can deteriorate rapidly, particularly in children 1
• Do not confuse incidental hyperglycemia (especially in young children with acute illness) with new-onset diabetes—"stress hyperglycemia" can occur without true diabetes 1, 2
• Do not perform routine screening for type 1 diabetes in asymptomatic children outside of research studies or first-degree relatives of patients with type 1 diabetes 1, 2

Special Considerations for Children

For OGTT in children and adolescents, use a glucose load of 1.75 g/kg body weight (maximum 75g). 1, 2