Insulin suppresses endotoxin-induced oxidative, nitrosative, and inflammatory stress in humans.
Level 3 - non-randomized controlled study
Controlled clinical trial with two parallel intervention groups; randomization is not stated in the abstract.
PubMed 20699433 · doi:10.2337/dc10-0929
What was done
Nineteen healthy volunteers were administered an intravenous lipopolysaccharide (LPS) challenge (2 ng/kg from Escherichia coli). Nine subjects received LPS alone, and ten subjects received LPS along with a 6-hour continuous insulin infusion (2 units/h) and 5% dextrose (100 ml/h) to maintain euglycemia. Investigators measured plasma markers of oxidative and nitrosative stress, inflammatory mediators, adipokines, and tissue damage.
What was found
The abstract reports directional and qualitative findings without numerical values or confidence intervals. LPS alone induced rapid elevations in nitric oxide metabolites (NOM), thiobarbituric acid-reacting substances (TBARS), polymorphonuclear leukocyte (PMNL) reactive oxygen species (ROS) generation, free fatty acids, myoglobin, and inflammatory markers (TNF-α, IL-6, MCP-1, MIF, CRP, resistin, visfatin, LBP, and HMG-B1). Insulin co-infusion completely prevented the rise in NOM, free fatty acids, and TBARS, and significantly lowered PMNL ROS generation, plasma MIF, visfatin, and myoglobin. Insulin had no effect on LPS-induced increases in TNF-α, MCP-1, IL-6, LBP, resistin, or HMG-B1.
Why it matters
The study shows that insulin suppresses specific oxidative, nitrosative, and tissue-injury pathways during acute human endotoxemia, even though it leaves major upstream pro-inflammatory cytokines such as TNF-α and IL-6 unaffected.
Limits
The study is very small (n=19 total across two arms). The abstract does not specify whether subjects were randomized or if outcome assessments were blinded. No exact baseline or post-infusion numerical data, effect sizes, or p-values are reported in the abstract. Findings from an acute experimental LPS challenge in healthy participants cannot be directly extrapolated to clinical sepsis or systemic infection.
Cited by
- supports Lipopolysaccharide (LPS) entering the bloodstream induces an inflammatory response, elevating levels of TNF-alpha, interleukin-6, and MCP-1.