Best Test for Insulin Resistance
For adults with BMI >25, fasting insulin levels >15 mU/L directly confirm insulin resistance, but the oral glucose tolerance test (OGTT) with 2-hour glucose values is the most sensitive test for early detection of insulin resistance before fasting abnormalities appear. 1
Practical Testing Algorithm
First-Line Screening Approach
Start with fasting plasma glucose (FPG) as your initial screening test because it is convenient, inexpensive, reproducible, and widely available. 2 However, recognize that FPG primarily detects diabetes rather than early insulin resistance. 1
- FPG ≥126 mg/dL indicates diabetes (requires confirmation on separate day) 2
- FPG 100-125 mg/dL indicates impaired fasting glucose (IFG), suggesting insulin resistance 2
- Normal FPG does not exclude insulin resistance 1
Most Sensitive Test for Early Insulin Resistance
The OGTT is more sensitive and can detect insulin resistance before fasting glucose becomes elevated. 1 This test involves measuring glucose at baseline and 2 hours after a 75-gram glucose load. 2
- 2-hour glucose 140-199 mg/dL indicates impaired glucose tolerance (IGT), representing early insulin resistance 2, 1
- 2-hour glucose ≥200 mg/dL indicates diabetes 2
- The OGTT is poorly reproducible and difficult to perform in practice, limiting its routine use 1
Direct Insulin Measurement
Fasting insulin levels provide direct confirmation of insulin resistance when elevated. 1
A weighted combination of fasting insulin and triglycerides provides better sensitivity than fasting insulin alone for screening insulin resistance in the general population. 3 The formula Mffm/I = exp[2.63 - 0.28ln(insulin) - 0.31ln(triglycerides)] improves detection accuracy. 3
Sensitivity Ranking for Early Detection
From most to least sensitive for earliest insulin resistance detection: 1
- OGTT with 2-hour glucose
- Combined fasting insulin + glucose (QUICKI or HOMA indices)
- Combined fasting insulin + triglycerides
- Fasting plasma glucose
- HbA1c (5.7-6.4% suggests prediabetes with underlying insulin resistance) 2, 1
- Fasting insulin alone
Critical Testing Pitfalls to Avoid
Always test in the true fasting state (minimum 8 hours without caloric intake) to avoid postprandial variations that invalidate results. 1, 2
For Asian Americans, use the lower BMI threshold of ≥23 kg/m² rather than ≥25 kg/m² when determining who needs testing, as they have equivalent diabetes risk at lower BMI values. 2, 1
The euglycemic insulin clamp is the gold standard research method but is impractical for clinical use, requiring specialized equipment and expertise. 4, 5, 6 Reserve this for research settings only.
When to Use Each Test
Use FPG for routine screening in asymptomatic adults with BMI ≥25 kg/m² and additional risk factors (first-degree relative with diabetes, high-risk ethnicity, hypertension, dyslipidemia, PCOS, physical inactivity, history of gestational diabetes). 2
Use OGTT when FPG is normal but clinical suspicion for insulin resistance remains high based on physical signs (acanthosis nigricans, central obesity) or metabolic abnormalities. 2, 1
Measure fasting insulin directly when you need definitive confirmation of insulin resistance in patients with borderline glucose values or when considering insulin-sensitizing therapy. 1
Consider HbA1c (≥5.7%) as an alternative screening test that doesn't require fasting, though it is less sensitive for early insulin resistance than OGTT. 2, 1 Note that hemoglobinopathies and conditions affecting red cell turnover invalidate HbA1c results. 2
Confirmation Strategy
Repeat abnormal screening tests on a different day to confirm the diagnosis, especially for borderline values near diagnostic thresholds. 2 If two different tests (e.g., FPG and HbA1c) are both above diagnostic thresholds, diagnosis is confirmed without additional repeat testing. 2