What are the diagnostic criteria and treatment options for insulin resistance?

Diagnosing Insulin Resistance

Insulin resistance is diagnosed primarily through fasting plasma glucose (100-125 mg/dL indicating impaired fasting glucose), fasting insulin levels (>15 mU/L suggesting insulin resistance), or hemoglobin A1C (5.7-6.4% indicating prediabetes), with the diagnosis strengthened when multiple markers are present alongside clinical risk factors. 1

Risk Assessment and Screening Indications

Before testing, identify patients at risk who warrant evaluation:

• Overweight or obesity: BMI ≥25 kg/m² (or ≥23 kg/m² in Asian Americans) 1, 2
• Family history: First-degree relative with type 2 diabetes 1
• High-risk ethnicity: American Indian, African American, Hispanic, Asian/Pacific Islander 1
• Physical signs: Acanthosis nigricans (dark, velvety skin patches in body folds), central/abdominal obesity 1, 2
• Associated conditions: Polycystic ovary syndrome, hypertension (≥140/90 mmHg), dyslipidemia (HDL <35 mg/dL or triglycerides >250 mg/dL) 1, 2
• Age: Begin screening at age 35-45 years in adults without other risk factors 3, 2

Diagnostic Testing Approach

Primary Diagnostic Tests (Choose One or More)

Fasting Plasma Glucose (FPG)

• Impaired fasting glucose: 100-125 mg/dL indicates insulin resistance/prediabetes 1, 2
• Requires 8-hour fast 3
• Most practical first-line test 2

Fasting Insulin Levels

• Normal: <15 mU/L 1
• Borderline high: 15-20 mU/L 1
• High (insulin resistance): >20 mU/L 1
• Must be performed in fasting state 1

Hemoglobin A1C

• Prediabetes/insulin resistance: 5.7-6.4% 1, 2
• Reflects average glucose over 2-3 months 2
• Does not require fasting 2

Oral Glucose Tolerance Test (OGTT)

• Impaired glucose tolerance: 2-hour glucose 140-199 mg/dL after 75g glucose load 1, 2
• More sensitive but less practical than FPG or A1C 2

Interpretation Algorithm

1. If FPG 100-125 mg/dL OR A1C 5.7-6.4% OR 2-hour OGTT 140-199 mg/dL: Diagnose prediabetes, which indicates likely insulin resistance 1, 3

2. If fasting insulin >15 mU/L: This directly suggests insulin resistance, particularly when >20 mU/L 1

3. Strongest evidence for insulin resistance: Combination of elevated fasting insulin (>20 mU/L) with impaired fasting glucose or elevated A1C 1, 4

4. Simple clinical decision rule (from validation study): Diagnose insulin resistance if ANY of the following:

   • BMI >28.9 kg/m² 4
   • HOMA-IR >4.65 (corresponding to fasting insulin ~20.7 µU/mL) 4
   • BMI >27.5 kg/m² AND HOMA-IR >3.60 (corresponding to fasting insulin ~16.3 µU/mL) 4

Confirmatory and Supplementary Testing

C-peptide Measurement

• Measure alongside insulin to differentiate endogenous insulin production from exogenous administration 1
• Simultaneous elevation of both insulin and C-peptide confirms endogenous hyperinsulinism (insulin resistance) 1
• Isolated elevated C-peptide without hypoglycemia reflects insulin resistance rather than pathological hyperinsulinism 1

Lipid Profile and Blood Pressure

• Check as part of comprehensive evaluation for associated metabolic abnormalities 1
• Supports diagnosis when abnormal alongside glucose/insulin markers 2

Critical Pitfalls to Avoid

Testing Conditions

• Always perform testing in fasting state (except A1C) to avoid postprandial variations that confound interpretation 1
• Ensure at least 8-hour fast before FPG or insulin measurements 3

Confounding Factors

• Document medications affecting glucose metabolism (corticosteroids, atypical antipsychotics) when interpreting results 1
• Avoid diagnosis during acute illness: Stress hyperglycemia temporarily mimics insulin resistance and should not be used for diagnosis 1
• A1C limitations: Hemoglobinopathies, anemia, or recent blood transfusion may affect accuracy 3

Confirmation Requirements

• In absence of clear symptoms, confirm abnormal results with repeat testing on a subsequent day 3
• Single test may be insufficient; multiple abnormal markers strengthen diagnosis 1, 4

Distinguishing from Type 1 Diabetes

• In younger patients or those without typical type 2 risk factors, consider islet autoantibody testing to exclude type 1 diabetes 3
• Type 2 diabetes with insulin resistance does not involve autoimmune beta-cell destruction 2

Follow-up Testing

• If tests are normal: Repeat screening at minimum 3-year intervals 2, 3
• If prediabetes/insulin resistance diagnosed: Retest annually 2, 3
• More frequent testing warranted if BMI is increasing or additional risk factors develop 2

Clinical Context

The 2024 American Diabetes Association guidelines emphasize that insulin resistance exists on a continuum, with risk rising disproportionately as glucose and A1C values increase 2. While the hyperinsulinemic-euglycemic clamp remains the gold standard for research, it is impractical for clinical use 5, 6. The combination of fasting glucose, insulin, and A1C provides adequate diagnostic accuracy for clinical practice 1, 4. Most patients with type 2 diabetes have peripheral insulin resistance with relative (not absolute) insulin deficiency 2.