What are the diagnostic criteria and treatment options for diabetes in adults and children?

How to Diagnose Diabetes

Diabetes is diagnosed when fasting plasma glucose (FPG) is ≥126 mg/dL, hemoglobin A1C is ≥6.5%, 2-hour plasma glucose during a 75-g oral glucose tolerance test (OGTT) is ≥200 mg/dL, or random plasma glucose is ≥200 mg/dL in a patient with classic symptoms of hyperglycemia. 1, 2

Diagnostic Criteria

Any one of the following four criteria establishes the diagnosis:

• FPG ≥126 mg/dL (7.0 mmol/L) with fasting defined as no caloric intake for at least 8 hours 1, 2
• 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during a 75-g OGTT 1, 2
• A1C ≥6.5% (48 mmol/mol) performed in a laboratory using an NGSP-certified method standardized to the DCCT assay 1, 2
• Random plasma glucose ≥200 mg/dL (11.1 mmol/L) in a patient with classic symptoms of hyperglycemia (polyuria, polydipsia, weight loss, polyphagia, fatigue, blurred vision) or hyperglycemic crisis 1, 2

Confirmation Requirements

Diagnosis requires confirmation with a repeat abnormal test on a subsequent day, unless the patient presents with unequivocal hyperglycemia or classic symptoms. 1, 3 A single random plasma glucose ≥200 mg/dL with typical symptoms is sufficient without repeat testing. 1

Test Selection and Practical Considerations

All three tests (FPG, 2-hour OGTT, A1C) are equally appropriate for diagnosis. 1 However, each has specific advantages and limitations:

• A1C advantages: No fasting required, greater preanalytical stability, less day-to-day variability during stress or illness 1
• A1C limitations: Should not be used for diagnosis in conditions with altered red blood cell turnover (hemoglobinopathies, anemia, pregnancy, hemodialysis, recent blood loss or transfusion, erythropoietin therapy)—use only plasma glucose criteria in these situations 3
• Point-of-care A1C assays should not be used for diagnosis unless FDA-cleared specifically for diagnostic purposes 2

For OGTT, ensure adequate carbohydrate intake of at least 150 g/day for 3 days prior to testing. 1, 3 In children and adolescents, use a glucose load of 1.75 g/kg (maximum 75 g). 2

Distinguishing Type 1 from Type 2 Diabetes

The presence of one or more islet autoantibodies distinguishes type 1 diabetes from other types. 2

• Primary autoantibody: Glutamic acid decarboxylase (GAD) should be measured first 2
• If GAD negative: Test for islet tyrosine phosphatase 2 (IA-2) and/or zinc transporter 8 (ZnT8) antibodies 2
• Autoantibody testing must be performed only in an accredited laboratory with established quality control 2
• Note: 5-10% of adult-onset type 1 diabetes may be autoantibody negative 2

Multiple positive autoantibodies indicate higher risk of progression to insulin dependence. 2 C-peptide testing is useful in insulin-treated patients to assess residual β-cell function, but should not be performed within 2 weeks of a hyperglycemic emergency as results may be misleading. 2

Screening Recommendations

Adults

Screening should begin at age 35 years for all adults, or earlier in adults of any age with overweight/obesity (BMI ≥25 kg/m² or ≥23 kg/m² in Asian Americans) who have one or more risk factors. 1

Risk factors include: 1

• First-degree relative with diabetes
• High-risk race/ethnicity (African American, Latino, Native American, Asian American, Pacific Islander)
• History of cardiovascular disease
• Hypertension (≥130/80 mmHg or on therapy)
• HDL cholesterol <35 mg/dL or triglycerides >250 mg/dL
• Polycystic ovary syndrome
• Physical inactivity
• Other conditions associated with insulin resistance (severe obesity, acanthosis nigricans)

If tests are normal, repeat screening at minimum 3-year intervals; if prediabetes is detected, screen annually. 1, 3 People with gestational diabetes should have lifelong testing at least every 3 years. 1

Children and Adolescents

Risk-based screening should be considered after onset of puberty or after age 10 years (whichever occurs earlier) in children with overweight (BMI ≥85th percentile) or obesity (BMI ≥95th percentile) who have one or more risk factors. 1

Special Populations

Screen people taking certain medications including glucocorticoids, statins, PCSK9 inhibitors, thiazide diuretics, some HIV medications, and second-generation antipsychotic medications. 1 For those on second-generation antipsychotics, screen at baseline, rescreen 12-16 weeks after medication initiation, and annually thereafter. 1

People with HIV should be screened for diabetes and prediabetes using a similar protocol, though A1C may underestimate glycemia and is not recommended for diagnosis in this population. 1

Screen people within 3-6 months following acute pancreatitis and annually thereafter; screen annually for chronic pancreatitis. 1

Common Pitfalls to Avoid

• Do not use A1C for diagnosis in hemoglobinopathies or conditions with altered red blood cell turnover—use only plasma glucose criteria 3
• Do not rely on point-of-care A1C for diagnosis unless specifically FDA-cleared 2
• Confirm diagnosis with repeat testing unless patient has unequivocal hyperglycemia with classic symptoms 1, 3
• In children with acute illness, incidental hyperglycemia may represent "stress hyperglycemia" rather than new-onset diabetes—do not diagnose without confirmation 2
• The metabolic state of untreated children with type 1 diabetes can deteriorate rapidly—make definitive diagnosis immediately to avoid treatment delays 2
• Screening for type 1 diabetes in asymptomatic children is currently recommended only in research settings or for first-degree family members 2