What labs are used to evaluate insulin resistance?

Laboratory Tests for Evaluating Insulin Resistance

The most appropriate laboratory tests for evaluating insulin resistance include fasting plasma glucose, fasting insulin levels, calculation of HOMA-IR, 2-hour oral glucose tolerance test, and hemoglobin A1C. 1

Primary Screening Tests

Fasting Tests

• Fasting Plasma Glucose (FPG)

  • Threshold for impaired fasting glucose: 100-125 mg/dL
  • Advantages: Inexpensive and widely available 1
  • Normal range: <100 mg/dL

• Fasting Insulin Levels

  • Normal: <15 mU/L
  • Borderline high: 15-20 mU/L
  • High: >20 mU/L 2, 1
  • Note: Patients with fasting insulin <9.9 μU/mL are unlikely to have insulin resistance, while those with levels >18.4 μU/mL are likely to have insulin resistance 3

• HOMA-IR (Homeostatic Model Assessment for Insulin Resistance)

  • Formula: Fasting insulin (μU/mL) × Fasting glucose (mmol/L) / 22.5
  • Cutoff for insulin resistance: ≥3.8 in adults 1
  • Provides a calculated estimate of insulin resistance

Additional Tests

• 2-hour Oral Glucose Tolerance Test (OGTT)

  • Threshold for impaired glucose tolerance: 140-199 mg/dL
  • More sensitive than FPG for detecting insulin resistance 1
  • Particularly useful when fasting insulin levels are in the indeterminate range (9.9-18.4 μU/mL) 3

• Hemoglobin A1C

  • Prediabetes range: 5.7-6.4%
  • Should be performed using NGSP-certified method 1
  • Reflects average blood glucose over previous 2-3 months

Testing Algorithm

1. Initial screening: Obtain FPG and fasting insulin levels for all patients, and calculate HOMA-IR 1

2. If initial tests are inconclusive: Perform 75g OGTT with glucose measurements at 0,1, and 2 hours 1

3. For high-risk individuals: Consider more comprehensive evaluation including:

   • FPG
   • 2-hour OGTT
   • Hemoglobin A1C
   • Fasting lipid panel 1

High-Risk Populations Requiring Testing

Testing should be considered in individuals who:

• Have BMI ≥85th percentile for age and sex (in children) or ≥25 kg/m² (in adults) 2, 1
• Have family history of type 2 diabetes in first- or second-degree relatives 2
• Belong to high-risk racial/ethnic groups (American Indian, African American, Hispanic/Latino, Asian American, Pacific Islander) 2
• Have signs of insulin resistance or associated conditions:
  • Acanthosis nigricans
  • Hypertension
  • Dyslipidemia
  • Polycystic ovary syndrome 2, 1

Important Considerations

• The gold standard for measuring insulin resistance is the euglycemic hyperinsulinemic clamp technique, but this is primarily used in research settings due to its complexity 2, 4

• Fasting insulin levels correlate better with insulin resistance in individuals with normal glucose tolerance (correlation -0.58 to -0.74) compared to those with impaired glucose tolerance or diabetes (correlation approximately -0.48) 5

• In patients with abnormal glucose tolerance, fasting insulin is a better marker of insulin resistance than post-load insulin levels 5

• OGTT is necessary to identify impaired glucose tolerance, as fasting tests alone may miss this condition in approximately 12% of patients 3

• For children and adolescents with risk factors, testing should begin at age 10 years or at onset of puberty, whichever occurs first, and should be repeated at minimum 3-year intervals 2, 1

Potential Pitfalls

• Failure to follow proper fasting requirements can lead to falsely elevated glucose levels 1

• Improper sample handling can cause glycolysis and falsely low glucose values 1

• Using non-standardized HbA1C testing can lead to inaccurate results 1

• Relying solely on fasting glucose without assessing insulin levels may miss early insulin resistance 1, 6

• Isolated post-challenge hyperglycemia (normal fasting glucose with impaired glucose tolerance) represents a distinct metabolic phenotype with greater insulin resistance than isolated fasting hyperglycemia 7