What is the diagnostic approach for an adult patient with risk factors such as obesity, family history, or physical inactivity for type 2 diabetes?

How Type 2 Diabetes is Diagnosed

Type 2 diabetes is diagnosed when any one of three tests meets diagnostic thresholds: fasting plasma glucose ≥126 mg/dL, hemoglobin A1C ≥6.5%, or 2-hour plasma glucose ≥200 mg/dL during a 75-g oral glucose tolerance test, with confirmation by repeat testing unless classic symptoms are present. 1, 2, 3

Diagnostic Criteria

The American Diabetes Association recognizes three equally appropriate tests for diagnosis 1, 2:

• Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L) - requires at least 8 hours of fasting 1, 4
• Hemoglobin A1C ≥6.5% - no fasting required, but must use a standardized laboratory method 1, 2, 3
• 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during 75-g oral glucose tolerance test (OGTT) 1, 2
• Random plasma glucose ≥200 mg/dL with classic hyperglycemic symptoms (polyuria, polydipsia, unintentional weight loss) - this alone is diagnostic without repeat testing 1, 5

Confirmation requirement: If the patient lacks classic symptoms, any positive test must be confirmed by repeat testing on a separate day using the same or a different diagnostic test 1, 2, 5. A single test suffices only when classic hyperglycemic symptoms are present 1.

Who Should Be Tested

Universal Screening Age

All adults should begin screening at age 35 years, regardless of other risk factors 1, 2. This represents the most recent guideline update from age 45 years 1.

Earlier Screening Based on Risk Factors

Test adults of any age who have BMI ≥25 kg/m² (or ≥23 kg/m² for Asian Americans) plus one or more of these risk factors 1, 2:

• First-degree relative with diabetes - this confers stronger genetic risk than most other factors 1, 6, 7
• High-risk race/ethnicity: African American, Latino, Native American, Asian American, or Pacific Islander 1
• Physical inactivity 1, 7
• History of cardiovascular disease 1
• Hypertension (≥140/90 mmHg or on antihypertensive therapy) 1
• HDL cholesterol <35 mg/dL or triglycerides >250 mg/dL 1
• Women with polycystic ovary syndrome 1
• Women with prior gestational diabetes 1
• Signs of insulin resistance: acanthosis nigricans, severe obesity 1

Critical BMI adjustment for Asian Americans: Use BMI ≥23 kg/m² as the threshold, as this population develops diabetes at approximately 15 pounds less weight than other groups 1, 2. Data show that one-third to one-half of diabetes in Asian Americans remains undiagnosed, suggesting current screening misses many cases 1.

Screening Frequency

• If tests are normal: Repeat at minimum 3-year intervals 1, 2
• If prediabetes is detected (A1C 5.7-6.4%, FPG 100-125 mg/dL, or 2-hour OGTT 140-199 mg/dL): Test annually 1, 2
• Higher-risk individuals: Consider more frequent testing (annually) even with normal results 1, 2

Prediabetes Identification

Prediabetes is defined by any of these criteria 1, 2:

• Impaired fasting glucose (IFG): FPG 100-125 mg/dL (5.6-6.9 mmol/L) 1
• Impaired glucose tolerance (IGT): 2-hour OGTT 140-199 mg/dL (7.8-11.0 mmol/L) 1
• Elevated A1C: 5.7-6.4% 1, 2

Individuals with A1C ≥5.7% have diabetes risk equivalent to high-risk Diabetes Prevention Program participants and require aggressive lifestyle intervention 2.

Special Populations and Considerations

Children and Adolescents

Test overweight children (BMI ≥85th percentile) starting at age 10 years or at puberty onset if they have maternal history of gestational diabetes, family history of type 2 diabetes in first- or second-degree relatives, or signs of insulin resistance 1.

Medications That Increase Risk

Consider earlier or more frequent screening in patients taking glucocorticoids, thiazide diuretics, certain HIV antiretroviral medications, or atypical antipsychotics 1.

HIV-Positive Patients

Follow a specific screening protocol, but avoid using A1C for diagnosis in this population as it may underestimate glycemia 1.

Younger Adults Without Traditional Risk Factors

Consider testing for islet autoantibodies (GAD65) to exclude type 1 diabetes if diabetes is diagnosed in younger adults without typical type 2 risk factors 1.

Common Diagnostic Pitfalls

A1C limitations: While convenient, A1C has a large overlap between normal, prediabetes, and mild diabetes ranges 5. A1C <6.5% does not exclude diabetes if other tests are positive 1, 5. A1C may be unreliable in certain conditions (hemoglobinopathies, anemia, HIV) 1.

OGTT variability: The oral glucose tolerance test has lower test-retest reliability than fasting glucose or A1C 8. However, OGTT identifies many cases that fasting glucose alone would miss, particularly in Asian populations 5.

Fasting requirements: Fasting plasma glucose requires a minimum 8-hour fast; non-fasting samples invalidate the test 1, 4.

Undiagnosed cases: Type 2 diabetes frequently remains undiagnosed for years because hyperglycemia develops gradually and early stages lack symptoms 1. Even undiagnosed patients face increased microvascular and macrovascular complication risks 1.