The metabolomic signature of weight loss in the Diabetes Remission Clinical Trial (DiRECT)

Abstract

AbstractUse of high-throughput metabolomics technologies in a variety of study designs has demonstrated a strong and consistent metabolomic signature of overweight and type 2 diabetes. However, the extent to which these metabolomic patterns can be recovered with weight loss and diabetes remission has not been investigated. We aimed to characterise the metabolomic consequences of a weight loss intervention in diabetes, within an existing randomised controlled trial – the Diabetes Remission Clinical Trial (DiRECT) – to provide insight into how weight loss-induced metabolic changes could lead to improved health. Decreases in branched chain amino acids, sugars and LDL triglycerides, and increases in sphingolipids, plasmalogens and metabolites related to fatty acid metabolism were associated with the intervention. The change in metabolomic pattern with mean 8.8kg weight loss thus reverses many features associated with the development of type 2 diabetes. Furthermore, metabolomic profiling also appears to capture variation in response to treatment seen across patients.