Metabolomic Analysis of the Improvements in Insulin Secretion and Resistance After Sleeve Gastrectomy: Implications of the Novel Biomarkers

Abstract

Background Large neutral amino acids (LNAAs) and gut microbial metabolites have been linked to insulin secretion and resistance. We investigated whether baseline LNAAs and kynurenine pathway metabolites and changes in tryptophan-derived gut microbial metabolites (TDGMs), such as indole compounds, were associated with improvements in insulin secretion and resistance after sleeve gastrectomy. Methods In this prospective single-arm longitudinal study, 23 patients with type 2 diabetes underwent sleeve gastrectomy. Twelve diabetes-related amino acid metabolites were quantified before surgery, and the following three indices were assessed as outcome measures: insulinogenic index, homeostasis model assessment-insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI). We also measured changes in TDGMs, including four indole compounds, 3 months after bariatric surgery. A linear regression model and receiver operating characteristic curves were assessed. Results The mean age and body mass index of study participants were 41.8 years (standard deviation (SD), 13.1 years) and 38.9 kg/m(2)(SD, 5.2 kg/m(2)), respectively. Several baseline amino acid metabolites were significantly associated with a change in insulin secretion or resistance 3 months after bariatric surgery. Phenylalanine and LNAAs showed superior performance for predicting improvements in insulin secretion and resistance. Among the TDGMs, Delta indole-3-propionic acid was significantly associated with the Delta insulinogenic index, and Delta indole-3-acetic acid was significantly associated with the Delta HOMA-IR and Delta QUICKI. Conclusions Our findings underscore the importance of baseline amino acid profiles, especially those of LNAAs and phenylalanine, and alterations in TDGMs for improving insulin secretion and resistance in the early postoperative period after sleeve gastrectomy.