What are the diagnostic criteria and initial management for type 1 diabetes?

Diagnosis of Type 1 Diabetes

Diagnostic Criteria

Type 1 diabetes is diagnosed by demonstrating hyperglycemia using standard glycemic criteria, followed by confirmation of autoimmune beta-cell destruction through islet autoantibody testing. 1, 2

Glycemic Thresholds (Any One of the Following)

• Fasting plasma glucose ≥126 mg/dL (7.0 mmol/L) after no caloric intake for at least 8 hours 1
• 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test (OGTT) 1
• HbA1c ≥6.5% (48 mmol/mol) performed in a laboratory using NGSP certified method 1
• Random plasma glucose ≥200 mg/dL (11.1 mmol/L) in a patient with classic symptoms of hyperglycemia 1, 3

Confirmation Requirements

• Two abnormal test results are required unless there is unequivocal hyperglycemia with classic symptoms or hyperglycemic crisis 4, 2
• The two tests can be performed at the same time or at two different time points 4
• If two different tests are both above diagnostic thresholds, this confirms the diagnosis 3
• In patients with classic symptoms (polyuria, polydipsia, weight loss) plus random glucose ≥200 mg/dL, immediate diagnosis can be made without waiting for confirmatory testing 2, 3

Type-Specific Confirmation: Autoantibody Testing

Glutamic acid decarboxylase (GAD) should be the primary antibody measured 4, 1

Sequential Testing Algorithm

• If GAD is negative, follow with islet tyrosine phosphatase 2 (IA-2) and/or zinc transporter 8 (ZnT8) antibodies 4, 1
• In individuals not yet treated with insulin, insulin autoantibodies (IAA) may also be useful 4
• The presence of two or more autoantibodies strongly confirms type 1 diabetes and indicates stage 1 disease even before clinical hyperglycemia develops 2
• All autoantibody tests should be performed only in an accredited laboratory with established quality control 1

Important Caveat About Autoantibody-Negative Cases

• 5-10% of adult-onset type 1 diabetes may be autoantibody negative 4, 1
• In individuals diagnosed at <35 years of age who have no clinical features of type 2 diabetes or monogenic diabetes, a negative autoantibody result does not change the diagnosis of type 1 diabetes 4

Clinical Presentation Features

Classic Symptoms

• Polyuria, polydipsia, weight loss, polyphagia, fatigue, and blurred vision 1
• Approximately one-third of type 1 diabetes patients present with diabetic ketoacidosis (DKA) at diagnosis, particularly children and adolescents 2, 3

Age-Specific Considerations

• In children and adolescents, an OGTT should use a glucose load of 1.75 g/kg (maximum 75 g) 1
• Incidental hyperglycemia without classic symptoms does not necessarily indicate new-onset diabetes, especially in young children with acute illness who may experience "stress hyperglycemia" 1
• The metabolic state of untreated children with type 1 diabetes can deteriorate rapidly, so a definitive diagnosis should be made immediately to avoid delays in treatment 1

Staging of Type 1 Diabetes

Type 1 diabetes develops in three distinct stages 1, 2:

• Stage 1: Presence of two or more islet autoantibodies with normoglycemia (no impaired glucose tolerance or impaired fasting glucose) 1
• Stage 2: Presence of two or more islet autoantibodies with dysglycemia (impaired fasting glucose and/or impaired glucose tolerance) 1
• Stage 3: Symptomatic disease with overt hyperglycemia meeting standard diagnostic criteria 1, 2

Distinguishing Type 1 from Type 2 Diabetes in Adults

When the clinical picture is unclear in adults, use this flowchart approach 4:

Step 1: Test Islet Autoantibodies

• If autoantibody positive: Diagnosis is type 1 diabetes 4
• If autoantibody negative in adults: Proceed to clinical assessment 4

Step 2: Clinical Assessment for Autoantibody-Negative Adults

Age <35 years without features of type 2 diabetes: Likely type 1 diabetes despite negative antibodies 4

Age >35 years: Make clinical decision based on features 4:

• Features suggesting type 2 diabetes: BMI ≥25 kg/m², absence of weight loss, absence of ketoacidosis, less marked hyperglycemia, features of metabolic syndrome 4
• Features suggesting type 1 diabetes: Normal or low BMI, significant weight loss, presence of ketoacidosis, marked hyperglycemia 4

Step 3: C-Peptide Testing (Only in Insulin-Treated Patients)

• C-peptide >600 pmol/L (>1.8 ng/mL): Suggests type 2 diabetes 4
• C-peptide 200-600 pmol/L: Indeterminate 4
• C-peptide <200 pmol/L: Suggests type 1 diabetes 4
• A random sample (with concurrent glucose) within 5 hours of eating can replace a formal C-peptide stimulation test 4
• Do not test C-peptide within 2 weeks of a hyperglycemic emergency as results may be misleading 4, 1

Step 4: Consider Monogenic Diabetes

Test for monogenic diabetes if any of these features are present 4:

• HbA1c <7.5% at diagnosis
• One parent with diabetes
• Features of a specific monogenic cause (renal cysts, partial lipodystrophy, maternally inherited deafness, severe insulin resistance without obesity)
• Monogenic diabetes prediction model probability >5%

Critical Pitfalls to Avoid

• Do not rely solely on HbA1c for diagnosis in conditions with altered relationship between HbA1c and glycemia (hemoglobinopathies, anemia) 1
• Point-of-care HbA1c assays should not be used for diagnosis unless FDA-cleared specifically for diagnostic purposes 1
• Use plasma glucose rather than HbA1c in individuals with symptoms of hyperglycemia for initial diagnosis 3
• In conditions with increased red blood cell turnover, only plasma glucose criteria should be used for diagnosis 2

Screening Considerations

• Screening for type 1 diabetes in asymptomatic children with autoantibody panels is currently recommended only in research settings or for first-degree family members of a person with type 1 diabetes 1, 3
• Persistence of two or more autoantibodies predicts clinical diabetes 3

Additional Testing After Diagnosis

Screen for additional autoimmune conditions soon after diagnosis 3:

• Test for antithyroid peroxidase and antithyroglobulin antibodies
• Screen for celiac disease by measuring IgA tissue transglutaminase (tTG) antibodies