Abstract 12671: Weight Loss Improves Cardiometabolic Health as Measured by Plasma Proteins in Individuals With Type 2 Diabetes

Abstract

Introduction: The DiRECT (UK cohort) and DIADEM-1 (Middle Eastern/North Africian cohort) trials in patients with type 2 diabetes demonstrated average weight loss of >10kg spurred by dietary intervention led to 46-61% diabetes remission at 12 months. Here we investigated cardiometabolic outcomes of these cohorts using predictive proteomic SomaSignal ® tests. Methods: Eight cardiometabolic SomaSignal tests (each derived from ~5000 plasma proteins measurements using aptamer-based proteomics assay) related to cardiometabolic health were assessed in baseline and 1-year samples in intervention (DiRECT n=118, DIADEM-1 n=66) and control (DiRECT n=144, DIADEM-1 n=76) participants. Results: Despite differences in baseline characteristics (age, ethnicity, diabetes duration, cardiovascular (CV) risk factors), both intervention groups showed similar improvements in overall cardiometabolic outcomes (Figure). Seven SomaSignal tests in DiRECT and six SomaSignal tests in DIADEM-1 significantly improved in the intervention groups compared to respective control arms. Liver fat, glucose intolerance, body fat percentage, resting metabolic rate, visceral fat, and cardiorespiratory fitness predictions significantly improved in intervention arms of both trials with greater relative improvements seen in individuals that lost >10kg. Additionally, CV risk improved significantly in the DiRECT intervention arm (which had higher baseline CV risk compared to DIADEM-1), as well as in both trials among individuals lost >10kg. Conclusion: Proteomic changes suggest widespread improvement in cardiometabolic traits, including CV risk, across both trials of intentional weight loss in individuals with type 2 diabetes. Notably, greater relative improvements in all traits including CV risk were seen in individuals that lost >10kg. These data suggest large intentional weight loss will improve future CV outcomes.