Definition
Insulin resistance is a metabolic condition in which the body's cells exhibit a diminished response to the hormone insulin, resulting in reduced glucose uptake and utilization despite normal or elevated circulating insulin levels.
Overview
Insulin resistance is a central feature of several common metabolic disorders, most notably type 2 diabetes mellitus and metabolic syndrome. The condition can develop gradually and is often asymptomatic in its early stages. Risk factors include obesity (particularly central adiposity), sedentary lifestyle, genetic predisposition, and certain pharmacologic agents. Persistent insulin resistance leads to compensatory hyperinsulinemia; over time, pancreatic β‑cells may fail to maintain adequate insulin secretion, precipitating hyperglycemia.
Etymology/Origin
The term combines “insulin,” the peptide hormone discovered in 1921 that regulates blood glucose, with “resistance,” derived from the Latin resistentia meaning “opposition” or “withstand.” The phrase “insulin resistance” entered the biomedical literature in the mid‑20th century as researchers described diminished cellular responsiveness to insulin.
Characteristics
- Cellular signaling impairment: Defects in the insulin receptor, post‑receptor signaling pathways (e.g., IRS‑1/2, PI3K/Akt), or glucose transporter (GLUT4) translocation reduce glucose uptake in muscle and adipose tissue.
- Hyperinsulinemia: Elevated plasma insulin concentrations are a compensatory response to maintain euglycemia.
- Elevated fasting glucose and impaired glucose tolerance: Measured by oral glucose tolerance tests or fasting plasma glucose levels.
- Associated metabolic alterations: Dyslipidemia (elevated triglycerides, low HDL‑cholesterol), hypertension, and increased inflammatory markers.
- Diagnostic indices: The Homeostatic Model Assessment of Insulin Resistance (HOMA‑IR) and the euglycemic‑hyperinsulinemic clamp are standard methods for quantifying insulin sensitivity.
Related Topics
- Type 2 diabetes mellitus
- Metabolic syndrome
- Obesity (especially visceral obesity)
- Hyperinsulinemia
- Glucose intolerance
- Cardiovascular disease risk factors
- Lifestyle interventions (diet, exercise) and pharmacologic agents (e.g., metformin, thiazolidinediones) used to improve insulin sensitivity.