Insulin Resistance – GP Guide

Insulin resistance (IR) is a metabolic condition where body tissues (muscle, liver, fat) become less responsive to insulin.

To compensate, the pancreas produces ↑ insulin (hyperinsulinemia) to maintain normal glucose levels.
Over time, this may lead to:

Type 2 diabetes mellitus (T2DM)
Cardiovascular disease (CVD)
Non-alcoholic fatty liver disease (NAFLD)

🔍 Key Features

Feature	Description
Pathophysiology	↓ Insulin signaling → ↓ glucose uptake (muscle/fat) + ↑ hepatic glucose output
Clinical Associations	T2DM, metabolic syndrome, PCOS, NAFLD
Progression	Often precedes T2DM by years; reversible in early stages with lifestyle change

Insulin resistance (IR) develops when the body’s cells—especially in muscle, liver, and fat—stop responding properly to insulin. This disruption involves a complex mix of cellular, hormonal, and genetic factors. IR is strongly linked to obesity, inflammation, and metabolic conditions like type 2 diabetes (T2DM) and polycystic ovary syndrome (PCOS).
The table below summarizes the key mechanisms driving this condition.

Mechanism	Description	Key References
↓ Insulin signaling	Disrupted receptor cascade → ↓ GLUT4 → ↓ glucose uptake	Abdul‐Ghani & DeFronzo, 2010
Lipotoxicity	↑ Diacylglycerol, ectopic fat → PKC activation → blocks signaling	Itani et al., 2002; Samuel & Shulman, 2012
Inflammation	↑ TNF-α, IL-6 → IRS serine phosphorylation → ↓ insulin action...

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