Polycystic Ovary Syndrome (PCOS) is increasing in prevalence worldwide and affects approximately 7–10% of women in Europe. It is the most common cause of female infertility. Insulin resistance is considered a key pathophysiological mechanism underlying the syndrome.
The gold standard for assessing insulin resistance is the euglycemic hyperinsulinemic clamp technique. This method evaluates insulin sensitivity by maintaining a constant blood glucose concentration during intravenous insulin and glucose administration. Although highly accurate, the procedure is complex, time-consuming, and difficult to implement in routine clinical practice.
For this reason, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) is widely used as a surrogate marker of insulin resistance. The HOMA-IR is calculated using fasting plasma glucose and fasting insulin concentrations according to the following formula:
Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated using fasting plasma glucose and fasting insulin concentrations according to the following equation:
When fasting glucose is expressed in mmol/L, the denominator is 22.5 instead of 405.
Interpretation of HOMA-IR values:
HOMA-IR Value | Interpretation |
< 2.0 | Insulin resistance unlikely |
2.0–2.5 | Possible insulin resistance |
> 2.5 | Insulin resistance likely |
A HOMA-IR value greater than 2.5 is generally considered suggestive of insulin resistance.
However, HOMA-IR should not be used to assess insulin resistance in patients with established type 2 diabetes mellitus, as its accuracy is limited in this population.
HOMA-IR correlates well with measurements obtained using the euglycemic clamp in individuals with normal glucose tolerance. However, the index may provide unreliable results in individuals with low body mass index (BMI), impaired pancreatic β-cell function, or markedly elevated fasting glucose levels. Consequently, HOMA-IR is not considered an appropriate tool for quantifying insulin resistance in patients with manifest type 2 diabetes mellitus.
Commentary
Several additional methods and indices have been developed to estimate insulin sensitivity and insulin resistance, including the Minimal Model, Quantitative Insulin Sensitivity Check Index (QUICKI), SPINA Carb, and others.
The Minimal Model approach is too complex for routine clinical practice, whereas QUICKI, SPINA Carb, and similar indices remain indirect estimations comparable to HOMA-IR and SPISE. Their applicability is therefore limited in certain clinical situations.
For example, these surrogate indices cannot reliably exclude polycystic ovary syndrome (PCOS), a condition that is intrinsically associated with insulin resistance. In clinical practice, normal index values are frequently observed despite the presence of significant metabolic abnormalities.
For this reason, listing all available surrogate methods offers little practical benefit, as none can replace comprehensive clinical evaluation when insulin resistance is strongly suspected.