Insulin Resistance

Deep dive

Insulin Resistance: complete reference

Insulin resistance (the glossary entry; also "insulin resistance" as condition) refers to the cellular state where body tissues become less responsive to insulin's signaling, requiring higher insulin levels to achieve normal glucose uptake. Mechanistically, insulin resistance involves post-receptor signaling defects, inflammatory cytokine interference (especially from visceral fat-derived adipokines), and downregulated GLUT4 glucose transporters в muscle/adipose. The compensatory hyperinsulinemia eventually overwhelms pancreatic beta-cell capacity, leading to type 2 diabetes. Insulin resistance is reversible: weight loss (especially visceral fat reduction), exercise (especially resistance + interval training), and dietary changes can restore sensitivity. GLP-1 medications improve insulin sensitivity through multiple mechanisms: weight loss (primary), direct effects on insulin signaling pathways в muscle/liver/adipose, and reduced inflammatory markers. Measurement: HOMA-IR ((fasting insulin × fasting glucose) / 405) — >2.5 suggests insulin resistance.

In practice

Before GLP-1: your pancreas pumps out 25 units of insulin to handle a meal. After 10% weight loss on Wegovy: your pancreas only needs 10 units for the same meal — insulin sensitivity restored.

Clinical context

Insulin resistance is the precursor to T2D. GLP-1 medications improve sensitivity through multiple pathways.