What are the initial steps to diagnose and manage a patient suspected of having diabetes type 1?

Testing to Determine Type 1 Diabetes

Measure plasma glucose to confirm hyperglycemia, then test for islet autoantibodies—specifically glutamic acid decarboxylase (GAD) antibodies first, followed by IA-2 and/or ZnT8 antibodies if GAD is negative—to definitively diagnose type 1 diabetes. 1

Confirming Hyperglycemia

The diagnosis begins with demonstrating elevated blood glucose using any of these criteria 1:

• Random plasma glucose ≥200 mg/dL (11.1 mmol/L) in a patient with classic symptoms (polyuria, polydipsia, weight loss) is immediately diagnostic 2, 3
• Fasting plasma glucose ≥126 mg/dL (7.0 mmol/L) after 8 hours without caloric intake 1
• 2-hour plasma glucose ≥200 mg/dL during oral glucose tolerance test 1
• HbA1c ≥6.5% using NGSP-certified laboratory method 1

Critical distinction: If the patient presents with classic hyperglycemic symptoms or diabetic ketoacidosis (which occurs in approximately one-third of type 1 diabetes presentations), a single random plasma glucose ≥200 mg/dL is sufficient—no repeat testing needed. 2, 3 However, if symptoms are absent or the clinical picture is unclear, you must obtain two abnormal test results from separate samples to confirm diabetes. 2, 1

Important caveat: Use plasma glucose rather than HbA1c for initial diagnosis in symptomatic patients, as HbA1c can be unreliable in conditions affecting red blood cell turnover (hemoglobinopathies, anemia). 1, 3 Point-of-care HbA1c devices should never be used for diagnosis unless specifically FDA-cleared for this purpose. 1

Confirming Autoimmune Etiology

Once hyperglycemia is established, autoantibody testing distinguishes type 1 from type 2 diabetes 1:

Testing Algorithm

1. Start with GAD (glutamic acid decarboxylase) antibodies as the primary test 1
2. If GAD is negative, proceed to test IA-2 (islet tyrosine phosphatase 2) and/or ZnT8 (zinc transporter 8) antibodies 1
3. Insulin autoantibodies (IAA) can also be measured but are less commonly used in clinical practice 3

The presence of one or more positive autoantibodies confirms type 1 diabetes. 3 Two or more positive autoantibodies indicate stage 1 disease and strongly predict progression to clinical diabetes. 1, 3

When Autoantibodies Are Negative

If autoantibodies are negative in an adult with apparent diabetes, proceed with clinical assessment considering 1:

• Features suggesting type 2 diabetes (obesity, metabolic syndrome, family history)
• C-peptide testing to assess residual insulin production
• Possibility of monogenic diabetes in select cases

A small subset of patients have "idiopathic type 1 diabetes"—they have permanent insulin deficiency and DKA risk but no detectable autoimmunity. This is more common in individuals of African or Asian ancestry. 2

Additional Diagnostic Testing at Presentation

Beyond confirming the diagnosis, obtain these baseline assessments 4:

• Urinalysis for ketones, protein, and sediment to detect DKA and establish baseline renal status 4
• Serum creatinine to establish baseline kidney function 4
• HbA1c if not already measured during diagnosis (guides treatment targets) 4
• Fasting lipid profile (total cholesterol, HDL, LDL, triglycerides) for cardiovascular risk assessment 4

Screening for Associated Autoimmune Conditions

Screen for other autoimmune diseases soon after diagnosis 1, 3:

• Thyroid function: Measure TSH when clinically stable, plus antithyroid peroxidase and antithyroglobulin antibodies (more predictive of future thyroid dysfunction than TSH alone) 4
• Celiac disease: Test IgA tissue transglutaminase (tTG) antibodies plus total serum IgA level 4, 1, 3

This screening is critical because celiac disease affects 1.6-16.4% of type 1 diabetes patients versus only 0.3-1% of the general population. 4 Patients with type 1 diabetes are also at increased risk for Hashimoto thyroiditis, Graves disease, Addison disease, vitiligo, autoimmune hepatitis, myasthenia gravis, and pernicious anemia. 2

Common Pitfalls to Avoid

• Don't assume obesity rules out type 1 diabetes. While patients are not typically obese at presentation, obesity is increasingly common and may even be a risk factor for type 1 diabetes. 2
• Don't delay the second confirmatory test. If using two separate samples, perform the second test "without delay" per guidelines. 2, 1
• Don't confuse insulin autoantibodies (IAA) with antibodies that develop after exogenous insulin therapy. IAA must be measured before insulin treatment begins to be diagnostically useful. 3
• Don't use autoantibody screening in asymptomatic individuals outside of research settings, except for first-degree relatives of patients with type 1 diabetes where it can be offered as an option. 2, 3

Staging Type 1 Diabetes

Type 1 diabetes progresses through three stages 1:

• Stage 1: Two or more islet autoantibodies with normoglycemia
• Stage 2: Two or more islet autoantibodies with dysglycemia (abnormal glucose but not meeting diabetes criteria)
• Stage 3: Symptomatic disease with overt hyperglycemia requiring insulin

This staging framework is primarily relevant for research and screening contexts, particularly with the recent approval of teplizumab to delay progression from stage 2 to stage 3. 5