HOMA-2: Homeostatic Model Assessment Insulin Resistance 2

The Homeostatic Model Assessment 2 (HOMA-2) is an algorithm used to assess insulin resistance and pancreatic beta-cell function in patients. Its calculation considers only two blood analytes:

• Glucose
• Insulin

Pancreatic beta cells are a specialized subtype of endocrine cells within the pancreas. Their primary role is the secretion of insulin, the hormone responsible for regulating glucose metabolism and maintaining blood sugar levels. Specifically, insulin performs the following functions:

• Facilitates glucose uptake into cells.
• Promotes glycolysis (breakdown of glucose).
• Stimulates glycogenesis (synthesis of glycogen).
• Enhances protein synthesis.
• Encourages lipid synthesis.
• Inhibits gluconeogenesis (synthesis of glucose).
• Suppresses protein degradation.

When blood glucose levels rise, beta cells secrete insulin into the bloodstream, facilitating glucose uptake by various body cells. There, glucose is either metabolized for energy or stored as glycogen. Many organs and tissues in the body have insulin receptors, with the highest concentrations found in the liver, skeletal muscles, and adipose tissue. Once blood glucose levels decrease, insulin is broken down.

Insulin levels in the blood increase significantly at the start of a meal, coinciding with a marked rise in blood glucose levels. In contrast, fasting insulin levels are much lower but never reach zero, as the pancreas maintains a constant basal insulin secretion. This fine-tuned balance between blood glucose and insulin levels ensures precise and rigorous control of glucose metabolism.

Disruptions in insulin secretion can lead to several diseases, with diabetes being the most significant. The two primary types of diabetes are:

• Type 1 Diabetes Mellitus: An autoimmune disease where the immune system attacks and destroys pancreatic beta cells. This results in a substantial reduction in insulin production and a rapid rise in blood glucose levels.
• Type 2 Diabetes Mellitus: A condition often associated with obesity. Through complex mechanisms, cells become resistant to insulin, leading to insulin resistance and glucose accumulation in the bloodstream. Initially, beta cells increase insulin production to compensate for high glucose levels. However, as the disease progresses, glucose accumulation becomes overwhelming, and insulin production becomes insufficient. If untreated, insulin resistance progresses to prediabetes and eventually to type 2 diabetes mellitus, where insulin levels are wholly inadequate to manage glucose. The progression of type 2 diabetes is much slower than type 1 but is far more prevalent and alarming due to the global obesity epidemic.

By calculating HOMA-2, healthcare professionals can estimate the functionality of beta cells based on the relationship between blood glucose and insulin levels. Abnormal HOMA-2 results may indicate disruptions in glucose metabolism, such as insulin resistance. Additionally, the HOMA-2 index can suggest conditions such as prediabetes or type 1 or type 2 diabetes mellitus, depending on the results obtained.

HOMA-IR and HOMA-2 differ in the mathematical formulas used to calculate their respective indices. As such, the results derived from both algorithms can complement one another, offering a more precise assessment of the patient’s beta-cell function.