48-LB: Changes in Plasma Levels of Nonnutritive Sweetener Erythritol Are Related to Two-Year Changes of Insulin Sensitivity in Response to Weight-Loss Diets—The POUNDS Lost trial

Evidence on the benefits of non-nutritive sweeteners for weight management and improving insulin sensitivity and glucose metabolism is inconsistent. Recently, high levels of circulating erythritol, a sugar alcohol used as one of the non-nutritive sweeteners, have been linked to increased risks of type 2 diabetes and its vascular complications. Whether changes in circulating erythritol levels are related to insulin sensitivity and glucose metabolism remains unknown. Here, we investigated whether changes in plasma erythritol induced by weight-loss diet interventions were related to improved insulin sensitivity and glucose metabolism. This study included overweight or obese participants without diabetes or unstable cardiovascular disease from the POUNDS Lost trial with available data on circulating erythritol at baseline (n=805) and its changes from baseline to 6 months (n=670) and 2 years (n=533) during weight-loss diet interventions. At baseline, higher plasma levels of erythritol were related to hyperinsulinemia and greater degrees of insulin resistance assessed by HOMA-IR, even after adjusting for covariates, including BMI (P <0.05 for all). In response to weight-loss dietary interventions, a greater decrease in plasma erythritol was significantly associated with larger reductions of fasting insulin (p= 0.0001) and HOMA-IR (p=0.039) at 6 months, regardless of the initial levels of BMI, erythritol, and the respective outcome. Similarly, we found a significant association between long-term changes in erythritol and a 2-year reduction of fasting insulin (p=0.0027). In conclusion, circulating plasma erythritol, a marker of non-nutritive sweetener consumption, was significantly associated with hyperinsulinemia and insulin sensitivity among adults with overweight or obesity. Weight-loss diet-induced decreases in plasma erythritol were related to improved insulin sensitivity. Disclosure Y. Heianza: None. Q. Xue: None. J. Rood: None. G. Bray: Advisory Panel; Medifast, Inc., Herbalife International of America, Inc. F. Sacks: None. L. Qi: None. Funding National Institutes of Health (DK091718, DK100383, DK115679, 2P20GM109036-06A1-7233)