What lab tests are used to check for insulin resistance?

Laboratory Tests for Insulin Resistance

The most appropriate laboratory tests for evaluating insulin resistance are fasting plasma glucose, 2-hour oral glucose tolerance test, fasting insulin levels, and calculation of the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). 1, 2

Primary Diagnostic Tests

First-Line Tests

• Fasting Plasma Glucose (FPG)

  • Threshold for impaired fasting glucose: 100-125 mg/dL (5.6-6.9 mmol/L) 2
  • Advantages: Inexpensive, widely available 2
  • Requires 8-hour fast; false results may occur with improper fasting or sample handling 2

• 2-hour Oral Glucose Tolerance Test (OGTT)

  • Threshold for impaired glucose tolerance: 140-199 mg/dL (7.8-11.0 mmol/L) 2
  • More sensitive than FPG for detecting insulin resistance 2
  • Requires patient preparation with at least 150g carbohydrate intake for 3 days prior 2

• Fasting Insulin Levels

  • Normal: <15 mU/L
  • Borderline high: 15-20 mU/L
  • High: >20 mU/L 2
  • Accounts for approximately 40% of variability in direct measures of insulin-mediated glucose disposal 3

Calculated Indices

• HOMA-IR (Homeostatic Model Assessment for Insulin Resistance)
  • Formula: Fasting insulin (μU/mL) × Fasting glucose (mmol/L) / 22.5
  • Cutoff for insulin resistance: ≥3.16 in adolescents 4, ≥3.8 in adults 5
  • More reliable than fasting glucose/insulin ratio for assessing insulin resistance 4
  • Highly correlated with more complex measures of insulin sensitivity 3, 6

Additional Tests to Consider

• Hemoglobin A1C

  • Prediabetes range: 5.7-6.4% (39-47 mmol/mol) 2
  • Can be used for HOMA-IR calculation as an alternative to fasting glucose 7
  • Should be performed using NGSP-certified method 2

• Lipid Profile

  • Total cholesterol, LDL, HDL, and triglycerides 1
  • Insulin resistance is associated with elevated triglycerides and decreased HDL 3

Testing Algorithm

1. Initial Screening:

   • FPG and fasting insulin levels for all patients with suspected insulin resistance
   • Calculate HOMA-IR using these values

2. If Initial Tests Inconclusive:

   • Perform 75g OGTT with glucose measurements at 0,1, and 2 hours
   • Consider HbA1C measurement

3. For Patients with Clinical Features of Insulin Resistance:

   • Complete lipid profile
   • Consider additional testing based on clinical presentation (e.g., testosterone levels for women with menstrual irregularities) 1

Special Considerations

• Acanthosis Nigricans: Presence strongly suggests insulin resistance and warrants comprehensive testing including FPG, OGTT, HbA1C, fasting insulin, and lipid panel 1

• High-Risk Populations: More frequent testing recommended for:

  • Individuals with BMI ≥25 kg/m² (lower in some ethnic groups)
  • Family history of type 2 diabetes
  • High-risk ethnic groups (African American, Latino, Native American, Asian American, Pacific Islander)
  • History of cardiovascular disease 2

• Follow-up Testing: Repeat testing at minimum 3-year intervals or more frequently if BMI increases 1

Common Pitfalls

• Fasting requirements not strictly followed, leading to falsely elevated glucose levels
• Improper sample handling causing glycolysis and falsely low glucose values 2
• Using point-of-care HbA1C testing that is not FDA-approved or NGSP-certified 2
• Relying solely on fasting glucose without assessing insulin levels, which may miss early insulin resistance 2, 3

HOMA-IR remains the most practical and reliable surrogate measure of insulin resistance in clinical settings when more complex procedures like euglycemic clamp are not feasible 3, 4.