What are the diagnostic criteria and methods for insulin resistance?

Diagnosing Insulin Resistance

The most effective approach to diagnose insulin resistance is through a combination of clinical assessment and laboratory testing, including fasting insulin levels, HOMA-IR calculation, and glucose tolerance testing when indicated. 1

Clinical Assessment for Insulin Resistance Risk

• Physical examination findings:

  • Acanthosis nigricans (velvety, hyperpigmented skin plaques in intertriginous areas)
  • Obesity, particularly central/abdominal obesity
  • Signs of polycystic ovary syndrome in women

• Risk factors warranting screening:

  • BMI ≥25 kg/m² (≥23 kg/m² in Asian Americans) 2
  • Family history of type 2 diabetes in first-degree relatives
  • High-risk ethnicity (African American, Latino, Native American, Asian American, Pacific Islander)
  • History of cardiovascular disease
  • Hypertension (≥140/90 mmHg or on therapy)
  • HDL cholesterol <35 mg/dL and/or triglycerides >250 mg/dL
  • Polycystic ovary syndrome
  • Physical inactivity
  • Other conditions associated with insulin resistance 2

Laboratory Testing

First-line Testing

• Fasting insulin levels:

  • Normal: <15 mU/L
  • Borderline high: 15-20 mU/L
  • High (indicating insulin resistance): >20 mU/L 1

• HOMA-IR calculation:

  • Formula: (Fasting insulin [μU/mL] × Fasting glucose [mg/dL])/405
  • Value ≥3.8 indicates insulin resistance 1
  • Advantages: Simple, requires only fasting measurements

Additional Testing When Indicated

• Oral Glucose Tolerance Test (OGTT):

  • Particularly valuable when fasting insulin levels fall in the intermediate range (9.9-18.4 μU/mL) 3
  • Measures glucose and insulin at baseline and after 75g glucose load
  • Allows calculation of insulin sensitivity indices:
    • ISI composite (insulin sensitivity index)
    • Area under the curve of insulin (AUCI)

• Prediabetes markers (indicating insulin resistance):

  • Fasting plasma glucose: 100-125 mg/dL (impaired fasting glucose)
  • 2-hour OGTT glucose: 140-199 mg/dL (impaired glucose tolerance)
  • HbA1c: 5.7-6.4% 2, 1

Testing Algorithm

1. Initial screening: Fasting insulin and glucose with HOMA-IR calculation

   • If fasting insulin <9.9 μU/mL: Insulin resistance unlikely 3
   • If fasting insulin >20 μU/mL: Insulin resistance likely 1
   • If fasting insulin 9.9-20 μU/mL: Proceed to OGTT

2. OGTT when indicated:

   • Measure glucose and insulin at 0,30,60,90, and 120 minutes
   • Calculate insulin sensitivity indices
   • Assess for impaired glucose tolerance

3. Consider additional metabolic assessment:

   • Fasting lipid panel (particularly triglycerides)
   • A weighted score combining fasting insulin and triglycerides can improve sensitivity for detecting insulin resistance 4

Special Considerations

• The euglycemic hyperinsulinemic clamp is the gold standard for measuring insulin resistance but is primarily used in research settings due to complexity 1, 5

• In children and adolescents, testing should be considered after puberty onset or after age 10 (whichever occurs earlier) if BMI ≥85th percentile with one or more additional risk factors 2

• Fasting requirements must be strictly followed (8-12 hours) to avoid falsely elevated glucose levels 1

• Insulin resistance and hyperinsulinemia are independent risk factors for cardiovascular events, even in patients with normal glucose tolerance 6

• If tests are normal, repeat testing at minimum 3-year intervals is recommended, or more frequently if BMI is increasing 2, 1