Abstract MPWE46: Changes in Plasma Imidazole Propionate and Long-term Successful Weight Loss in Response to Dietary Interventions: POUNDS Lost trial

Introduction: Imidazole propionate (ImP), a histidine-derived metabolite produced by gut microbiota, has been recently linked to the risk of cardiovascular events. Hypothesis: We tested whether temporal changes in circulating ImP were associated with long-term weight loss outcomes among adults with overweight or obesity in a weight-loss dietary intervention trial. Methods: This study included 597 participants (58% women; mean (SD) age 51.6 (9.0) years) from the 2-year weight loss dietary intervention called the POUNDS Lost trial. We measured plasma ImP levels at baseline and 6 months, and changes were calculated. The primary outcomes were change in body weight and waist circumference over 2 years. Long-term successful weight loss was defined as weight loss of –5% or more at 1 year and 2 years compared to the initial body weight; the probability of achieving successful weight loss was calculated using logistic regression. Results: Before the interventions, a higher ImP level at baseline was related to higher body mass index and estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk. A greater decrease in ImP levels in response to the interventions was significantly associated with greater reductions of body weight (β per 1 SD decrease of log-transformed ImP = –1.17 kg, SE 0.25, p <0.001) and waist circumference (β = –0.82 cm, SE 0.27, p =0.003) after adjusting for covariates, including the initial ImP levels. We also found that the initial (6-month) decrease in ImP levels was significantly associated with the long-term (2-year) reductions of body weight (β = –0.89 kg, SE 0.38, p =0.021) and waist circumference (β = –0.84 cm, SE 0.39, p =0.032). Greater initial decrease in ImP levels was significantly associated with 1.5 and 1.3 times higher probability of achieving long-term successful weight loss at 1 year and 2 years, respectively ( p <0.05) Conclusions: Decrease in circulating ImP levels in response to dietary interventions was associated with long-term successful weight loss among adults with overweight and obesity, suggesting its potential as a predictive biomarker for weight management.