What tests are used to diagnose insulin resistance?

Diagnostic Tests for Insulin Resistance

The most clinically useful tests for insulin resistance include fasting plasma glucose, oral glucose tolerance test (OGTT), and hemoglobin A1C, with fasting insulin levels providing a reasonable clinical alternative when specific insulin resistance assessment is needed. 1

Primary Diagnostic Methods

First-Line Testing

• Fasting Plasma Glucose (FPG)

  • Threshold: ≥126 mg/dL (7.0 mmol/L) indicates diabetes
  • Requires at least 8 hours of fasting
  • Simple, inexpensive office screening tool 1

• Hemoglobin A1C

  • Threshold: ≥6.5% (48 mmol/mol) indicates diabetes
  • Must be performed using NGSP-certified method standardized to DCCT assay
  • No fasting required; reflects average glycemia over 2-3 months 1

• 2-hour Plasma Glucose during OGTT

  • Threshold: ≥200 mg/dL (11.1 mmol/L) indicates diabetes
  • Uses 75g glucose load
  • More sensitive than FPG alone for detecting insulin resistance 2

Assessment of Insulin Resistance Specifically

• Fasting Insulin Levels
  • Normal: <15 mU/L
  • Borderline high: 15-20 mU/L
  • High: >20 mU/L
  • Reasonable clinical alternative for evaluating insulin resistance 1

Advanced/Research Methods

• Euglycemic Insulin Clamp

  • Gold standard for measuring insulin resistance
  • Involves continuous IV insulin and glucose over 3 hours
  • Currently used only for research purposes 1, 3

• Insulin Suppression Test

  • Direct assessment of insulin-mediated glucose utilization
  • Labor and time intensive
  • Primarily for research settings 3

• Surrogate Indices

  • HOMA (Homeostatic Model Assessment)
  • QUICKI (Quantitative Insulin Sensitivity Check Index)
  • Matsuda Index (from OGTT data)
  • These calculated indices can be used when more direct measurements aren't feasible 3, 4

Clinical Application Algorithm

1. Initial Screening:

   • For patients with risk factors (obesity, family history of diabetes, high-risk ethnicity, hypertension, dyslipidemia, acanthosis nigricans, PCOS)
   • Start with FPG and A1C 1

2. If initial tests are normal but insulin resistance is still suspected:

   • Proceed with 75g OGTT
   • Consider measuring fasting insulin levels 2
   • Note: Up to 14.4% of subjects with insulin resistance may be misclassified when using only fasting measurements 2

3. For confirmed cases or specialized assessment:

   • Consider referral to endocrinology if clinical picture is complex
   • Specialized testing may be warranted in research settings

Important Considerations and Pitfalls

• A1C limitations: Cannot be used in hemoglobinopathies, pregnancy, hemodialysis, recent blood loss/transfusion, or erythropoietin therapy 1

• Fasting insulin caveats:

  • Not standardized across laboratories
  • Not recommended for routine testing in most people with diabetes 1
  • Most useful when values are <9.9 μU/mL (likely no insulin resistance) or >18.4 μU/mL (likely insulin resistance) 5

• OGTT advantages:

  • More sensitive for detecting early insulin resistance
  • Better identifies individuals with postprandial hyperglycemia who have normal fasting values 2
  • Should be considered when fasting tests are normal but clinical suspicion remains high

• C-peptide measurement:

  • Not routinely recommended for insulin resistance assessment
  • Primarily useful for differentiating type 1 from type 2 diabetes in ambiguous cases 1

Early identification and treatment of insulin resistance is critical for preventing progression to type 2 diabetes and reducing cardiovascular risk, making appropriate diagnostic testing an essential component of clinical care.