What laboratory tests should be ordered to evaluate insulin resistance?

Laboratory Tests for Insulin Resistance

For clinical evaluation of insulin resistance, order fasting plasma glucose (FPG) and fasting plasma insulin, then calculate HOMA-IR using the formula: [fasting glucose (mmol/L) × fasting insulin (mU/mL)] ÷ 22.5. 1, 2

Primary Laboratory Tests

Fasting Plasma Glucose (FPG)

• Order FPG as the initial screening test - it is easy, inexpensive, and widely available for office-based assessment 3
• Values of 100-125 mg/dL indicate impaired fasting glucose (IFG), suggesting insulin resistance and prediabetes 3, 1
• Requires minimum 8-hour fast without caloric intake 3, 4
• Important caveat: Normal FPG does not exclude insulin resistance, as glucose abnormalities appear later in the disease process 3, 4

Fasting Plasma Insulin

• Directly measures hyperinsulinemia as a marker of insulin resistance 3, 1
• Interpretation thresholds 3, 1, 2:
  • Normal: <15 mU/L
  • Borderline high: 15-20 mU/L
  • High (insulin resistance): >20 mU/L
• Research shows fasting insulin alone performs comparably to HOMA-IR for identifying insulin resistance in nondiabetic individuals (r=0.98 correlation) 5

HOMA-IR Calculation

• Calculate HOMA-IR using: [fasting glucose (mmol/L) × fasting insulin (mU/mL)] ÷ 22.5 1, 2
• Values >2.5 consistently indicate pathological insulin resistance 2
• Most valid in non-diabetic individuals where pancreatic β-cells can still adapt to insulin resistance 1, 2
• Validity is questionable in established type 2 diabetes due to β-cell dysfunction 2

Secondary/Confirmatory Tests

Oral Glucose Tolerance Test (OGTT)

• More sensitive than FPG for detecting early insulin resistance, though poorly reproducible and difficult to perform 4
• Administer 75g glucose load after overnight fast 3
• 2-hour plasma glucose values of 140-199 mg/dL indicate impaired glucose tolerance (IGT), representing insulin resistance 3, 1, 4
• Use OGTT when FPG is normal but clinical suspicion remains high 4

Hemoglobin A1C

• Values of 5.7-6.4% suggest prediabetes with underlying insulin resistance 3, 1, 4
• Less sensitive than OGTT for early detection but more convenient 4

Lipid Profile

• Order lipid panel as part of comprehensive metabolic assessment 3, 1
• Elevated triglycerides and low HDL-cholesterol correlate with insulin resistance 5, 6
• A weighted combination of fasting insulin and triglycerides provides enhanced screening sensitivity 6

Clinical Evaluation Components

Physical Examination Findings to Document

• Acanthosis nigricans (hyperpigmented, velvety skin in body folds) - direct sign of insulin resistance 3, 1
• Central/abdominal obesity with increased waist circumference 3, 1
• Blood pressure measurement (hypertension associated with insulin resistance) 3, 1
• Signs of polycystic ovary syndrome in women 3

Risk Factors Requiring Testing

Test individuals with 3, 1, 4:

• BMI ≥25 kg/m² (or ≥23 kg/m² for Asian Americans)
• First-degree family history of type 2 diabetes
• High-risk race/ethnicity (American Indian, African American, Hispanic, Asian/Pacific Islander)
• History of gestational diabetes or delivering baby >9 lbs
• Hypertension (≥140/90 mmHg)
• Dyslipidemia (HDL <35 mg/dL or triglycerides >250 mg/dL)
• Physical inactivity

Testing Algorithm by Sensitivity

From most to least sensitive for earliest detection 4:

1. OGTT with 2-hour glucose measurement
2. Combined fasting insulin + glucose (HOMA-IR)
3. Combined fasting insulin + triglycerides
4. Fasting plasma glucose alone
5. HbA1C
6. Fasting insulin alone

Critical Pitfalls to Avoid

Testing Conditions

• Always test in true fasting state (minimum 8 hours without caloric intake) to avoid postprandial variations 3, 4
• Do not use stress hyperglycemia during acute illness for diagnosis - this temporarily mimics insulin resistance 1
• Note medications affecting glucose metabolism (corticosteroids, atypical antipsychotics) when interpreting results 3, 1

Test Limitations

• HOMA-IR lacks universally accepted cut-off values - interpret in clinical context 2
• Insulin assays vary widely between laboratories - establish proper reference values for your specific lab 2
• The euglycemic insulin clamp is the gold standard but requires 3-hour IV infusion and is impractical for clinical use (research only) 3, 2, 7

Guideline Cautions

• The American Diabetes Association does not recommend routine insulin or proinsulin measurement in most patients (Grade B evidence), considering these primarily research tools 2
• However, this conflicts with practical clinical need for insulin resistance assessment in high-risk populations 1, 2

Special Populations

Children and Adolescents

• Test after puberty onset or age 10 years, whichever comes first 3
• Requires overweight/obesity (≥85th percentile) PLUS additional risk factors 3
• Repeat testing every 3 years if normal, more frequently if BMI increasing 3

Asian Americans

• Use lower BMI threshold of ≥23 kg/m² rather than standard ≥25 kg/m² 1, 4

When to Repeat Testing

• Repeat at minimum 3-year intervals if initial tests normal 3
• Test more frequently if BMI increasing or risk factor profile deteriorating 3