How to Measure Insulin Resistance
For clinical practice, use the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) calculated from fasting glucose and fasting insulin levels, which provides a validated, practical alternative to the research-standard euglycemic clamp. 1, 2
Gold Standard Method (Research Only)
The euglycemic insulin clamp remains the reference standard but is impractical for routine clinical use. 1, 3 This technique requires:
- Continuous intravenous insulin and glucose infusion over 3 hours 1
- Calculation of insulin sensitivity based on glucose required to maintain euglycemia 1
- Specialized equipment and personnel, limiting its use to research settings 3, 4
Recommended Clinical Method: HOMA-IR
HOMA-IR is the most practical and validated method for assessing insulin resistance in clinical practice, particularly in non-diabetic individuals. 1, 2, 5
Calculation and Requirements
- Formula: HOMA-IR = [fasting glucose (mmol/L) × fasting insulin (mU/mL)] ÷ 22.5 5
- Both measurements must be obtained in the fasting state (8-12 hours) to avoid postprandial variations 2
- Proper reference values must be established for your specific laboratory, as insulin assays vary widely 5
Interpretation Thresholds
- HOMA-IR <2.0: Generally associated with normal insulin sensitivity 5
- HOMA-IR 2.0-2.5: Borderline insulin resistance 5
- HOMA-IR >2.5: Consistently indicates pathological insulin resistance 5
- HOMA-IR ≥3.0: Significant insulin resistance requiring intervention 5
Clinical Validity
HOMA-IR correlates well with the euglycemic clamp (r=0.747 in diabetic subjects, r=0.419 in non-diabetic subjects) and is more closely associated with visceral fat accumulation than fasting insulin alone. 6 It provides superior accuracy compared to fasting insulin levels alone for predicting insulin resistance. 6
Alternative Simple Methods
Fasting Plasma Insulin Levels
When HOMA-IR calculation is unavailable, fasting insulin alone provides reasonable clinical assessment: 1, 2
Glucose-Based Screening
For initial screening without insulin measurement: 2
- Fasting plasma glucose: 100-125 mg/dL indicates impaired fasting glucose (prediabetes) 2
- Oral glucose tolerance test: 2-hour glucose 140-199 mg/dL indicates impaired glucose tolerance 2
- Hemoglobin A1C: 5.7-6.4% suggests prediabetes and potential insulin resistance 2
Combined Index (Research Alternative)
A weighted score using fasting insulin and triglycerides provides higher sensitivity than fasting insulin alone: Mffm/I = exp[2.63 - 0.28ln(insulin) - 0.31ln(triglycerides)]. 7 However, this remains primarily a research tool.
Important Clinical Context
When HOMA-IR Is Most Valid
HOMA-IR is most accurate in non-diabetic individuals where pancreatic beta-cells can still adapt to insulin resistance. 1, 5 The validity becomes questionable in established type 2 diabetes because it depends on preserved beta-cell function. 5
Specific Clinical Applications
- Metabolic dysfunction-associated steatotic liver disease (MASLD): HOMA-IR assessment is recommended in adults without established type 2 diabetes to clarify metabolic dysfunction 1, 5
- Polycystic ovary syndrome: HOMA-IR serves as a metabolic outcome measure in clinical trials and practice 5
- Cardiovascular risk assessment: May be considered when metabolic syndrome components are present 1
Critical Pitfalls to Avoid
- Acute illness: Stress hyperglycemia during acute illness temporarily mimics insulin resistance and should not be used for diagnosis 2
- Medication effects: Note any medications affecting glucose metabolism (corticosteroids, thiazides, beta-blockers) when interpreting results 2
- Non-fasting samples: HOMA-IR requires fasting samples; postprandial measurements are invalid 2
- Established diabetes: HOMA-IR has limited validity in patients with overt diabetes due to impaired beta-cell function 5
- Laboratory variability: Insulin assays vary significantly between laboratories; establish local reference ranges 5
Methods NOT Recommended for Routine Clinical Use
The American Diabetes Association explicitly recommends against routine testing for insulin or proinsulin in most people with diabetes or at risk, stating these assays are useful primarily for research purposes. 5 Similarly, the American College of Obstetricians and Gynecologists does not recommend routine C-peptide or insulin measurements for conditions like polycystic ovary syndrome. 5
Clinical assessment using BMI and physical signs (acanthosis nigricans) is recommended over extensive laboratory testing for initial insulin resistance screening. 5