What is the diagnostic workup for type 1 (Type I) diabetes in adults?

Diagnostic Workup for Type 1 Diabetes in Adults

The diagnostic workup for type 1 diabetes in adults should include islet autoantibody testing (particularly GAD, IA-2, and ZnT8), C-peptide measurement, and standard glycemic assessments to confirm the diagnosis and distinguish from other diabetes types. 1

Initial Diagnostic Tests

Standard Glycemic Assessment

• A1C ≥ 6.5% using a method certified by the NGSP and standardized to the DCCT reference assay 1
• Fasting plasma glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L) after at least 8 hours of fasting 1
• 2-hour plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during a 75-g oral glucose tolerance test 1
• Random plasma glucose ≥ 200 mg/dL (11.1 mmol/L) in patients with classic symptoms of hyperglycemia or hyperglycemic crisis 1

Confirmation Requirements

• Unless there is a clear clinical diagnosis with classic symptoms and random glucose ≥200 mg/dL, confirmation with a second test is necessary 1
• This can be accomplished by two abnormal test results, either at the same time or at different time points 1

Type 1 Diabetes-Specific Testing

Autoantibody Testing

• Test for islet autoantibodies to confirm autoimmune etiology 1
  • Glutamic acid decarboxylase (GAD) - should be the primary antibody measured
  • If GAD negative, test for islet tyrosine phosphatase 2 (IA-2)
  • Zinc transporter 8 (ZnT8)
  • Insulin autoantibodies (if not already on insulin therapy)

C-peptide Testing

• Measure C-peptide levels to assess endogenous insulin production 1
  • Random C-peptide with concurrent glucose within 5 hours of eating
  • 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

Important Considerations for C-peptide Testing

• Only indicated in people already receiving insulin treatment 1
• Do not test within 2 weeks of a hyperglycemic emergency 1
• If result is <600 pmol/L and concurrent glucose is <4 mmol/L (<70 mg/dL), consider repeating the test 1
• Very low levels (<80 pmol/L) do not need to be repeated 1

Additional Workup Components

Clinical Assessment

• Evaluate for classic symptoms:
  • Polyuria
  • Polydipsia
  • Unintentional weight loss 1
• Assess for diabetic ketoacidosis (DKA) 1
• Consider age of onset (though type 1 can occur at any age) 1

Screening for Associated Autoimmune Conditions

• Screen for other autoimmune disorders commonly associated with type 1 diabetes: 1
  • Hashimoto thyroiditis
  • Graves disease
  • Celiac disease
  • Addison disease
  • Vitiligo
  • Autoimmune hepatitis
  • Myasthenia gravis
  • Pernicious anemia

Diagnostic Algorithm for Adults with Suspected Type 1 Diabetes

1. Initial glycemic assessment (A1C, FPG, or 2-h PG)
2. Test islet autoantibodies (GAD first, then IA-2 and/or ZnT8 if negative)
3. If autoantibody positive: Likely type 1 diabetes
4. If autoantibody negative:
   • For adults <35 years: Consider type 1 diabetes (5-10% of type 1 diabetes is autoantibody-negative) 1
   • For adults >35 years: Evaluate for features of type 2 diabetes
5. If diagnosis remains unclear: Test C-peptide after >3 years of diabetes duration 1

Common Pitfalls and Caveats

• Do not rely solely on A1C for diagnosis, as it has limited sensitivity compared to plasma glucose criteria. Studies show HbA1c ≥6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% defined by 2hPG 2
• Obesity does not rule out type 1 diabetes - while less common, type 1 diabetes can occur in individuals with obesity 1
• Adult-onset type 1 diabetes may have a slower progression than childhood-onset disease, with a more gradual decline in β-cell function 1
• Autoantibody-negative type 1 diabetes occurs in 5-10% of cases, particularly in individuals of African or Asian ancestry 1
• Point-of-care A1C assays are not recommended for diagnostic purposes despite NGSP certification 1

By following this systematic diagnostic approach, clinicians can accurately identify type 1 diabetes in adults, leading to appropriate treatment decisions that will reduce morbidity and mortality associated with misdiagnosis and delayed insulin therapy.