Insulin Resistance

Insulin resistance means that a given concentration of insulin moves less glucose than it should. It is tissue-specific rather than systemic: skeletal muscle takes up less glucose after a meal, the liver fails to shut down glucose production between meals, and adipose tissue keeps releasing free fatty acids when it should be storing. Beta cells compensate by secreting more insulin, so fasting glucose stays normal for years while fasting insulin climbs. Hyperglycaemia appears only when that compensation fails, which is why insulin resistance and diabetes are not the same finding.

The reference measurement is the hyperinsulinaemic-euglycaemic clamp, which infuses insulin at a fixed rate and reports the glucose infusion needed to hold plasma glucose steady. It is a research procedure, so most work uses surrogates such as HOMA-IR. The strongest associations are with ectopic lipid in liver and muscle rather than total fat mass, and weight loss of five to ten percent of body weight reliably improves the measured value.

Because it is a state rather than a disease, treating it is not automatically a clinical outcome. Metformin, thiazolidinediones, weight loss and exercise all improve insulin action by different routes, and the trials that matter measured glycaemia and cardiovascular events, not an index. Hepatic and peripheral resistance are also dissociable, and a fasting-based index mostly reflects the liver.

The frequent error is treating an improved surrogate as reversal. Any negative energy balance lowers fasting insulin within days, before body composition has changed much, so a compound tested alongside weight loss cannot claim a direct sensitising effect from a HOMA-IR delta. Supplements sold to fix insulin resistance rest on that confound, and a single fasting insulin value defines nothing.