How do you diagnose insulin resistance?

Diagnosing Insulin Resistance

The most effective way to diagnose insulin resistance is through a combination of clinical risk assessment and laboratory testing, including fasting plasma glucose, fasting insulin levels, oral glucose tolerance test, and hemoglobin A1C. 1

Clinical Risk Assessment

• Evaluate for risk factors that predispose to insulin resistance:
  • Overweight or obesity (BMI ≥25 kg/m² or ≥23 kg/m² in Asian Americans) 1
  • Family history of type 2 diabetes 1
  • Racial/ethnic predisposition (American Indian, African American, Hispanic, or Asian/Pacific Islander) 1
  • Physical signs including acanthosis nigricans (dark, velvety skin patches typically in body folds), hypertension, dyslipidemia, or polycystic ovary syndrome 1

Laboratory Diagnostic Tests

Primary Tests

• Fasting plasma glucose (FPG):

  • Values between 100-125 mg/dL indicate impaired fasting glucose, suggesting insulin resistance 1
  • Must be measured after at least an 8-hour fast 2

• Fasting plasma insulin levels:

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

• Oral glucose tolerance test (OGTT):

  • 2-hour glucose values of 140-199 mg/dL indicate impaired glucose tolerance, suggesting insulin resistance 1
  • Involves administering 75g of glucose and measuring blood glucose after 2 hours 2

• Hemoglobin A1C:

  • Values between 5.7-6.4% suggest prediabetes and potential insulin resistance 1, 2

Supplementary Tests

• C-peptide measurement:

  • Helps differentiate between endogenous insulin production and exogenous insulin administration 1
  • Simultaneous elevation of insulin and C-peptide suggests endogenous hyperinsulinism, indicating insulin resistance 1

• Lipid profile:

  • Elevated triglycerides (>150 mg/dL) and low HDL cholesterol (<40 mg/dL in men, <50 mg/dL in women) often accompany insulin resistance 1

Calculation-Based Methods

• Homeostasis Model Assessment of Insulin Resistance (HOMA-IR):

  • Formula: (Fasting insulin [μU/mL] × Fasting glucose [mg/dL])/405
  • Values >2.5 suggest insulin resistance 3, 4

• TyG Index (Triglycerides-Glucose Index):

  • Formula: Ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]
  • Can be useful when insulin testing is unavailable 5

Physical Examination

• Check for:
  • Acanthosis nigricans (particularly on the neck, axillae, and groin) 1
  • Central obesity (waist circumference >40 inches in men or >35 inches in women) 1
  • Blood pressure (>130/85 mmHg suggests metabolic syndrome) 1

Common Pitfalls to Avoid

• Testing should be performed in the fasting state to avoid postprandial variations that can affect results 1
• Medications that affect glucose metabolism should be noted when interpreting results 1
• Stress hyperglycemia during acute illness can temporarily mimic insulin resistance and should not be used for diagnosis 1
• Isolated elevated C-peptide without hypoglycemia generally reflects insulin resistance rather than pathological hyperinsulinism 1
• Relying on a single test without confirmation can lead to misdiagnosis 2

Diagnostic Algorithm

1. Identify patients with risk factors for insulin resistance
2. Perform fasting laboratory tests (glucose, insulin, lipid profile)
3. If fasting glucose is 100-125 mg/dL or fasting insulin is >15 mU/L, insulin resistance is likely 1
4. Consider OGTT if fasting tests are borderline or normal but clinical suspicion remains high 1
5. Calculate HOMA-IR if both fasting glucose and insulin are available 3, 4
6. If insulin testing is unavailable, consider using the TyG index as an alternative 5