Improvement in insulin resistance after gastric bypass surgery is correlated with a decline in plasma 2-hydroxybutyric acid

Background: Gastric bypass surgery for weight reduction often corrects dysglycemia in diabetic patients, but a full understanding of the underlying biochemical pathways continues to be investigated. Objectives: To explore the effects of weight loss by surgical and dietary interventions on plasma metabolites using both targeted and discovery-oriented metabolomics platforms. Setting: An academic medical center in the United States. Methods: Improvement in homeostatic model assessment for insulin resistance (HOMA-IR), as an index of insulin resistance, was compared at 6 months in 11 patients that underwent Roux-en-Y gastric bypass against 11 patients that were matched for weight loss in the Weight Loss Maintenance (WLM) program. Metabolites in plasma were evaluated by nontargeted gas chromatography/mass spectrometry for the potential detection of >1100 biochemical markers. Results: Among multiple metabolites detected, 2-hydroxybutyric acid (2-HBA) declined most significantly after 6 months in comparing patients that underwent Roux-en-Y gastric bypass with those in WLM (P <.001), corresponding with declines in HOMA-IR (P =.025). Baseline levels of 2-HBA for all patients were correlated with preintervention levels of HOMA-IR (R ² =.565, P <.001). Moreover, the changes in 2-HBA after 6 months were correlated with changes in HOMA-IR (R ² =.399, P =.0016). Conclusions: Correlation between insulin resistance and 2-HBA suggests the utility of the latter as an excellent biomarker for tracking glycemic improvement, and offers further insight into the pathways that control diabetes. This is the first report of a decline in 2-HBA in response to bariatric surgery.