Clinical Relevance of Serum Insulin Levels and HOMA Index in Clinical Practice
Measuring serum insulin levels and calculating the Homeostasis Model Assessment (HOMA) index provides a valuable surrogate estimate of insulin resistance in non-diabetic individuals and has specific clinical applications in metabolic disease management, particularly in non-alcoholic fatty liver disease (NAFLD/MASLD). 1
Understanding HOMA-IR
Definition and Calculation
- HOMA-IR is calculated as the product of fasting glucose (in mmol/L) and insulin (in mU/ml), divided by 22.5 1
- Serves as a surrogate marker for insulin resistance when more complex and expensive dynamic testing (like euglycemic clamp) is not feasible 1, 2
- HOMA-IR correlates well with insulin resistance measured by the gold standard euglycemic-hyperinsulinemic clamp method (r=0.747 in diabetic subjects, r=0.419 in non-diabetic subjects) 2
Advantages and Limitations
Advantages:
Limitations:
- Validity depends on insulin secretory capacity, making it less reliable in overt diabetes 1
- Lack of standardized insulin assays creates variability in results 1
- No universally accepted threshold defining insulin resistance 1
- Limited utility in patients on insulin therapy (though modified approaches exist) 4
Clinical Applications
1. NAFLD/MASLD Assessment
- HOMA-IR provides confirmation of altered insulin sensitivity in cases of diagnostic uncertainty for NAFLD/MASLD, especially in normal-weight individuals with ultrasound-defined steatosis 1
- During follow-up, HOMA-IR helps identify patients at risk of NASH (non-alcoholic steatohepatitis) or fibrosis progression 1
- Improvement in HOMA-IR during weight loss indicates metabolic improvement beneficial for NAFLD 1
2. Metabolic Syndrome Evaluation
- NAFLD/MASLD is tightly associated with insulin resistance in liver, muscle, and adipose tissues 1
- HOMA-IR assessment helps in comprehensive evaluation of metabolic syndrome components, which correlate with liver fat content 1
- Persistent or worsening metabolic abnormalities, including elevated HOMA-IR, are associated with liver disease progression 1
3. Diabetes Risk Assessment
- Assessment of insulin resistance using HOMA-IR may be considered to clarify metabolic dysfunction in individuals with suspected MASLD without established type 2 diabetes 1
- Useful in identifying individuals at risk of developing type 2 diabetes, particularly those with prediabetes 5
- HOMA-IR correlates with various metabolic parameters including:
4. Therapeutic Monitoring
- HOMA-IR can be used to monitor response to insulin-sensitizing therapies 1
- Improvement in HOMA-IR during weight loss correlates with metabolic improvement 1
- Can help assess the efficacy of lifestyle interventions and pharmacological treatments aimed at improving insulin sensitivity 5
Practical Considerations for Clinical Use
When to Measure
- In non-diabetic individuals with risk factors for insulin resistance:
Interpretation Challenges
- No universally accepted threshold defining insulin resistance using HOMA-IR 1
- Reference values should be established for specific populations 1
- HOMA-IR values are influenced by:
Alternative Approaches
- For patients with diabetes on insulin therapy, modified approaches for HOMA-IR calculation may be considered 4
- HbA1c-derived estimated average glucose can be used as an alternative to fasting glucose in HOMA-IR calculations, particularly when pre-analytical errors in glucose measurement are a concern 6
- HOMA2-IR, an updated computerized model, provides more accurate assessments of insulin sensitivity and beta-cell function 3
Conclusion
HOMA-IR provides a clinically useful assessment of insulin resistance, particularly valuable in the evaluation and management of NAFLD/MASLD and metabolic syndrome. While it has limitations, especially in patients with diabetes, it remains a practical tool for identifying individuals at risk for metabolic complications and monitoring response to interventions aimed at improving insulin sensitivity.