|
Getting your Trinity Audio player ready...
|
The Metabolic Root: Insulin Resistance and Some of Its Downstream Consequences
Insulin resistance — where cells stop responding effectively to insulin — is now recognised as the central upstream driver of a cluster of chronic conditions that medicine has historically treated as separate diseases.
The hepatic consequences are well established. When insulin signalling fails, the liver accumulates fat, producing Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD), which was called Non-alcoholic fatty liver disease. A 2024 UK Biobank study of 438,840 participants confirmed that MASLD carries a 16% higher all-cause mortality rate, with cardiovascular disease — not liver failure — as the leading cause of death in this population.
For a significant proportion of people, insulin resistance simultaneously drives hypertension through sodium retention, sympathetic nervous system activation, and endothelial dysfunction — though not universally, as genetic and constitutional factors determine individual susceptibility.
Less recognised, but equally well-supported, are the neurochemical consequences. Chronic low-grade inflammation — an invariable companion of insulin resistance — up-regulates the enzyme IDO, diverting tryptophan away from serotonin synthesis toward the neurotoxic kynurenine pathway. Simultaneously, inflammatory cytokines TNF-α and IL-6 suppress tyrosine hydroxylase, the rate-limiting enzyme in dopamine production. The result is a biochemically-driven depletion of both neurotransmitters.
Clinically, this manifests differently depending on individual constitution. Those with a more reactive nervous system baseline tend toward anxiety and hyperactivation; those with a slower, more anabolic constitution tend toward the heaviness and withdrawal characteristic of depression. Neither presentation is a separate condition — both are downstream expressions of the same metabolic dysfunction, insulin resistance.
Research published in Psychoneuroendocrinology and Brain, Behaviour – study URL here, and Immunity has consistently linked insulin resistance and hyperinsulinaemia to elevated depression and anxiety scores, independent of other confounding variables.
The implication is significant: treating these conditions in isolation, without addressing insulin resistance as the common root, addresses symptoms rather than cause.