Tryptophan-Derived Metabolites and Glutamate Dynamics in Fatal Insulin Poisoning: Mendelian Randomization of Human Cohorts and Experimental Validation in Rat Models

Insulin overdose may cause hypoglycemic encephalopathy. In this study, Mendelian randomization was employed to analyze changes in the serum metabolites of patients with hypoglycemic encephalopathy, and metabolomics analysis was conducted to detect differential metabolites in the serum of a rat model of hypoglycemic encephalopathy induced by insulin overdose. The results indicated an overall upward trend in the tryptophan metabolism pathway in patients with hypoglycemic encephalopathy and rats with hypoglycemic encephalopathy caused by insulin overdose, while serum glutamate levels declined. The metabolic changes in the tryptophan pathway provide new insights into the impact of hypoglycemia on brain function. The related products of the tryptophan metabolism pathway have a certain diagnostic value for hypoglycemic encephalopathy and forensic identification of insulin overdose-induced hypoglycemic encephalopathy death.