Metabolite signature of diabetes remission in individuals with obesity undergoing weight loss interventions.

ABSTRACT

OBJECTIVE: This observational study investigated metabolomic changes in individuals with type 2 diabetes (T2D) after weight loss. We hypothesized that metabolite changes associated with T2D-relevant phenotypes are signatures of improved health. METHODS: Fasting plasma samples from individuals undergoing bariatric surgery (n = 71 Roux-en-Y gastric bypass [RYGB], n = 22 gastric banding), lifestyle intervention (n = 66), or usual care (n = 14) were profiled for 139 metabolites before and 2 years after weight loss. Principal component analysis grouped correlated metabolites into factors. Association of preintervention metabolites was tested with preintervention clinical features and changes in T2D markers. Association between change in metabolites/metabolite factors and change in T2D remission markers, homeostasis model assessment of ß-cell function, homeostasis model assessment of insulin resistance, and glycated hemoglobin (HbA1c) was assessed. RESULTS: Branched-chain amino acids (BCAAs) were associated with preintervention adiposity. Changes in BCAAs (valine, leucine/isoleucine) and branched-chain ketoacids were positively associated with change in HbA1c (false discovery rate q value ≤ 0.001) that persisted after adjustment for percentage weight change and RYGB (p ≤ 0.02). In analyses stratified by RYGB or other weight loss method, some metabolites showed association with non-RYGB weight loss. CONCLUSIONS: This study confirmed known metabolite associations with obesity/T2D and showed an association of BCAAs with HbA1c change after weight loss, independent of the method or magnitude of weight loss.