HOMA-IR (Insulin Resistance)

Mechanisms of insulin resistance: accumulation of diacylglycerols in myocytes and hepatocytes (causes GLUT4 transporter dysfunction and IRS phosphorylation), chronic low-grade inflammation (IL-6 and TNF-α reduce insulin signalling), increased visceral fat with free fatty acid spillover to the liver, intestinal dysbiosis with metabolic endotoxemia (LPS), mitochondrial dysfunction (reduced fatty-acid oxidation).

Insulin resistance is the core of metabolic syndrome — defined by at least 3 of: increased waist, high triglycerides, low HDL, high glucose or treatment, hypertension. It predicts type 2 diabetes, MAFLD, infarction, stroke, dementia, certain cancers, and all-cause mortality.

Factors that raise HOMA-IR: diet high in simple sugars and refined carbohydrates, sedentarism, insufficient or fragmented sleep, chronic stress, elevated visceral fat, dysbiosis, MAFLD, and sarcopenic obesity.

Interventions that lower HOMA-IR (ordered by potency): strength + Zone 2 exercise (acute and chronic effect), 16:8 or 14:10 intermittent fasting, visceral fat loss, Mediterranean or low-carbohydrate diet, supplements (berberine, myo-inositol, alpha-lipoic acid, omega-3 ≥2 g/day EPA+DHA, magnesium), and, in selected profiles, metformin or GLP-1 analogues.