What labs should be checked for an adult patient with a body mass index (BMI) of 25 or higher, or a history of gestational diabetes or polycystic ovary syndrome (PCOS), suspected of having insulin resistance?

Laboratory Testing for Insulin Resistance

For adults with BMI ≥25 kg/m² (or ≥23 kg/m² in Asian Americans) with history of gestational diabetes or PCOS, start with fasting plasma glucose (FPG) as the initial screening test, but add a 2-hour oral glucose tolerance test (OGTT) when FPG is normal yet clinical suspicion remains high, as OGTT detects early insulin resistance before fasting abnormalities appear. 1, 2

Primary Screening Tests

The three guideline-recommended tests are equally appropriate for detecting prediabetes and insulin resistance 1:

• Fasting Plasma Glucose (FPG): Most practical first-line test due to convenience, low cost, and reproducibility 1, 2

  • Normal: <100 mg/dL (5.6 mmol/L) 1
  • Impaired Fasting Glucose (IFG): 100-125 mg/dL (5.6-6.9 mmol/L) indicates insulin resistance 1
  • Diabetes: ≥126 mg/dL (7.0 mmol/L) - requires confirmation on separate day 1

• 2-Hour Oral Glucose Tolerance Test (OGTT): Most sensitive for early insulin resistance detection 2, 3

  • Use 75-gram glucose load after 8-hour fast 1
  • Normal: <140 mg/dL (7.8 mmol/L) 1
  • Impaired Glucose Tolerance (IGT): 140-199 mg/dL (7.8-11.0 mmol/L) represents early insulin resistance 1, 2, 3
  • Diabetes: ≥200 mg/dL (11.1 mmol/L) 1

• Hemoglobin A1C: Convenient alternative requiring no fasting, though less sensitive for early insulin resistance than OGTT 2, 4

  • Normal: <5.7% (39 mmol/mol) 1
  • Prediabetes: 5.7-6.4% (39-47 mmol/mol) 1, 4
  • Diabetes: ≥6.5% (48 mmol/mol) 1

Algorithmic Approach for Your Patient Population

Step 1: Order FPG as initial screening 1, 2

• Ensure true fasting state (minimum 8 hours without caloric intake) 1, 2, 3
• For Asian Americans, use BMI threshold of ≥23 kg/m² rather than ≥25 kg/m² 1, 2

Step 2: Interpret FPG results and determine next steps 1

• If FPG ≥126 mg/dL: Diabetes confirmed (repeat on different day) 1
• If FPG 100-125 mg/dL: Insulin resistance present (IFG) 1
• If FPG <100 mg/dL but high clinical suspicion: Proceed to OGTT 2, 3

Step 3: Add OGTT when indicated 2, 3

OGTT is particularly important for patients with history of gestational diabetes or PCOS because normal FPG does not exclude insulin resistance in these populations 2. The 2-hour glucose value detects abnormalities before fasting glucose becomes elevated 3.

Step 4: Consider A1C as adjunctive test 1, 4

• Can be drawn simultaneously with FPG for convenience 1
• Useful when fasting compliance is questionable 2
• Less sensitive than OGTT for early detection 2, 4

Tests NOT Routinely Recommended

Direct insulin measurements are not recommended for routine screening 1:

• Fasting insulin levels lack standardized reference values and cutoff thresholds 4
• HOMA-IR (calculated from fasting glucose and insulin) is not endorsed as a standalone screening test by major diabetes guidelines 4
• C-peptide measurements are reserved for distinguishing type 1 from type 2 diabetes in ambiguous cases, not for insulin resistance screening 1

The American College of Obstetrics and Gynecology specifically states that routine insulin or C-peptide measurements have no advantage over assessment of physical signs (BMI, acanthosis nigricans) in PCOS patients 1.

Critical Testing Pitfalls to Avoid

• Never test in non-fasting state: Postprandial variations invalidate FPG results 1, 2, 3
• Confirm abnormal results: Single elevated glucose requires repeat testing on different day unless unequivocal hyperglycemia present 1
• Recognize A1C limitations: Hemoglobin variants, anemia, pregnancy (second/third trimester), recent blood loss/transfusion, or erythropoietin therapy make A1C unreliable - use only glucose criteria in these situations 1
• Don't rely solely on FPG in high-risk populations: Normal FPG does not exclude insulin resistance, particularly in gestational diabetes and PCOS patients 2, 3

Follow-Up Testing Intervals

• If all tests normal: Repeat at minimum 3-year intervals 1
• If prediabetes detected (A1C ≥5.7%, IFG, or IGT): Test annually 1
• History of gestational diabetes: Lifelong testing at least every 3 years 1

Special Considerations for PCOS and Gestational Diabetes History

Women with PCOS demonstrate distinct hormonal responses to glucose load compared to those with gestational diabetes history, but both groups show decreased insulin sensitivity even when lean 5, 6. Both populations warrant the same screening approach outlined above, with particular emphasis on OGTT when FPG is normal 2, 3. PCOS increases risk for gestational diabetes, making screening particularly important in this population 7.