Diagnosing Insulin Resistance
The most practical clinical approach to diagnose insulin resistance is through fasting plasma glucose testing, particularly in at-risk individuals, with fasting plasma insulin levels providing a reasonable clinical alternative for direct evaluation of insulin resistance (normal <15 mU/L, borderline 15-20 mU/L, high >20 mU/L). 1
Risk Assessment for Insulin Resistance
Identifying individuals at risk for insulin resistance should be the first step in assessment:
- 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 of insulin resistance including acanthosis nigricans, hypertension, dyslipidemia, or polycystic ovary syndrome 1
- Sedentary lifestyle 2
Diagnostic Tests for Insulin Resistance
Primary Diagnostic Methods:
- Fasting plasma glucose (FPG): Values between 100-125 mg/dL (5.6-6.9 mmol/L) indicate impaired fasting glucose, suggesting insulin resistance 1
- Fasting plasma insulin levels: Normal <15 mU/L, borderline high 15-20 mU/L, high >20 mU/L 1
- Oral glucose tolerance test (OGTT): 2-hour glucose values of 140-199 mg/dL (7.8-11.0 mmol/L) indicate impaired glucose tolerance, suggesting insulin resistance 1, 2
- Hemoglobin A1C: Values between 5.7-6.4% suggest prediabetes and potential insulin resistance 1
Advanced or Research Methods:
- Euglycemic insulin clamp: The gold standard for measuring insulin resistance but used primarily for research purposes due to its complexity and invasive nature 1
- Homeostasis Model Assessment of Insulin Resistance (HOMA-IR): Calculated from fasting glucose and insulin levels, provides a reasonable estimate of insulin resistance 3, 4
- TyG index: The product of fasting triglycerides and glucose levels can serve as a surrogate marker for insulin resistance in settings where insulin testing is unavailable 5
Clinical Evaluation
A comprehensive clinical evaluation should include:
- Physical examination: Look specifically for acanthosis nigricans (dark, velvety skin patches, especially in neck folds and axillae), central obesity, and signs of associated conditions 1
- Laboratory assessment: Beyond glucose parameters, check lipid profile (particularly triglycerides) and blood pressure 1
- Evaluation for comorbidities: Screen for conditions commonly associated with insulin resistance, including hypertension, dyslipidemia, fatty liver disease, and polycystic ovary syndrome 1
Interpreting Results
- The presence of impaired fasting glucose (100-125 mg/dL) or impaired glucose tolerance (2-hour OGTT 140-199 mg/dL) indicates prediabetes and likely insulin resistance 1
- Elevated fasting insulin levels (>15 mU/L) directly suggest insulin resistance 1
- The combination of elevated fasting glucose and elevated triglycerides strongly suggests insulin resistance 5
Special Considerations
- Differential metabolic characteristics: Subjects with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) have different metabolic profiles; those with IGT tend to have more severe insulin resistance 6
- C-peptide measurement: When evaluating hyperinsulinemia, measuring C-peptide alongside insulin can help differentiate between endogenous insulin production (as in insulin resistance) and exogenous insulin administration 7
- Simultaneous elevation of insulin and C-peptide: This suggests endogenous hyperinsulinism, which may indicate insulin resistance or potentially an insulinoma if accompanied by hypoglycemia 7
Common Pitfalls and Caveats
- Insulin resistance testing should be performed in the fasting state to avoid postprandial variations 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 7