Production of insulin resistance by hyperinsulinaemia in man.
Level 3 - non-randomized controlled study
Controlled human crossover intervention study; randomization not specified in abstract.
PubMed 3884419 · doi:10.1007/BF00279918
What was done
Healthy volunteers were studied on two occasions: once after 40 hours of sustained hyperinsulinaemia (plasma insulin 25-35 mU/l via continuous insulin infusion) and once after a control saline infusion (plasma insulin ~10 mU/l). Following each infusion period, glucose utilization, endogenous glucose production, and overall glucose metabolism were measured during submaximal (~80 mU/l) and maximal (~1700 mU/l) plasma insulin concentrations. In vitro insulin binding was also assessed in isolated monocytes and adipocytes.
What was found
After 40 hours of hyperinsulinaemia, glucose utilization and overall glucose metabolism at submaximal and maximal insulin concentrations were slightly but significantly reduced compared with saline infusion (p < 0.05). Endogenous glucose production rates were unaffected. Monocyte and adipocyte insulin binding were also unaffected. The reduction in maximal insulin response alongside unchanged insulin binding indicates that the induced insulin resistance occurred at a post-binding site. No absolute values or numerical effect sizes were provided in the abstract.
Why it matters
This study provides experimental evidence in humans that physiological hyperinsulinaemia of the magnitude seen in obesity can directly induce peripheral insulin resistance via post-receptor mechanisms.
Limits
The abstract does not report sample size, participant demographics, exact numerical values for metabolic rates, or whether the crossover order was randomized or blinded. A 40-hour exposure in healthy individuals may not fully capture the complex, multi-tissue dynamics of chronic long-term hyperinsulinaemia in clinical metabolic disease.
Cited by
- supports High levels of insulin itself directly cause insulin resistance in humans, rodents, and cell cultures.