How do I interpret fasting insulin levels in a patient?

Interpreting Fasting Insulin Levels

Fasting insulin measurement is primarily a research tool and is not recommended for routine clinical use in most patients with or at risk for diabetes or cardiovascular disease. 1, 2

When Fasting Insulin Testing IS Indicated

Essential Clinical Scenarios

• Investigation of non-diabetic hypoglycemia to rule out surreptitious insulin administration 1, 2, 3
• Diagnosis of insulinoma: Persistently elevated insulin with low glucose strongly suggests islet cell tumor, particularly when the proinsulin-to-insulin ratio is increased 1, 3
• Distinguishing type 1 from type 2 diabetes in ambiguous cases (though C-peptide is preferred): Measure when fasting glucose ≤220 mg/dL 1, 2

Research and Specialized Contexts

• Marker of insulin resistance in research settings, particularly in individuals with normal glucose tolerance 2
• Evaluation of metabolic syndrome components in children and adolescents at high risk for type 2 diabetes 2

Reference Values and Thresholds

Normal Ranges (Population-Based Studies)

The evidence shows considerable variation in reference ranges depending on population and methodology:

• Iranian adults: 2-12 μU/mL for both genders (95% reference interval) 4
• French population (IMx-Abbott assay):
  • Women 30-49 years: median 5.1 μU/mL, 95th percentile 11.2 μU/mL 5
  • Men 30-64 years and women 50-64 years: median 5.6 μU/mL, 95th percentile 12.6 μU/mL 5
• Brazilian metabolically normal individuals: Mean 4.6 ± 1.8 mU/L (men), 5.6 ± 2.3 mU/L (women) 6

Hyperinsulinemia Thresholds

For identifying insulin resistance and metabolic syndrome, use these cut-offs:

• Men: ≥8 mU/L 6
• Women: ≥10 mU/L 6

These thresholds (mean + 2 SD from metabolically normal individuals) correlate with increased risk of metabolic syndrome progression, hepatic steatosis, and cardiovascular complications 6.

Clinical Interpretation Algorithm

Step 1: Assess Clinical Context

• If hypoglycemia present with low glucose: Measure insulin, C-peptide, and proinsulin simultaneously 1, 3
  • Elevated insulin + elevated C-peptide + low glucose = possible insulinoma 3
  • Elevated insulin + suppressed C-peptide = exogenous insulin administration 3
  • Elevated proinsulin-to-insulin ratio = strongly suggests insulinoma 1, 3

Step 2: Evaluate for Insulin Resistance (If Testing Performed)

• Normal weight patients with 1-2 metabolic syndrome criteria + insulin ≥8 mU/L (men) or ≥10 mU/L (women): Consider Level 1 metabolic syndrome with early intervention 6
• Patients with ≥3 metabolic syndrome criteria + hyperinsulinemia: Level 2 metabolic syndrome with higher risk of complications 6

Step 3: Age and Sex Considerations

• Fasting insulin shows a decreasing trend with age in both genders 4
• Men tend to have slightly higher median values than women across age groups 5
• Values increase after age 50 in women and after age 60 in men 5

Important Clinical Caveats

Common Pitfalls to Avoid

• Do not use fasting insulin routinely for diabetes diagnosis or screening – HbA1c and fasting glucose remain the tests of choice 1, 2
• Do not use insulin measurements for routine management of PCOS – physical signs (BMI, acanthosis nigricans) are equally informative 1
• Assay variability matters: Enzyme immunoassays that don't cross-react with proinsulin provide more specific results than conventional methods 5

When NOT to Order Fasting Insulin

• Routine diabetes screening or monitoring 1, 2
• Standard cardiovascular risk assessment 1, 2
• Typical type 2 diabetes management 1

Special Populations

• Pregnant women: Fasting insulin levels are substantially higher postprandially than in non-pregnant women 2
• Hypertensive patients: 50-66% may have elevated fasting insulin (>2 SD above controls), correlating with obesity and diabetes status 7

Prognostic Significance

High fasting insulin independently predicts type 2 diabetes even after accounting for insulin resistance, suggesting a primary pathogenic role of relative hyperinsulinemia 8. This finding supports early intervention in patients with elevated fasting insulin and metabolic syndrome criteria, rather than waiting for full diagnostic confirmation 6.