721-P: Mechanisms of Relapse after Lifestyle Intervention–Induced Remission of Prediabetes

In type 2 diabetes, relapse after remission is characterized by a loss of recovered beta cell function and re-accumulation of ectopic lipids. Mechanistic insights on relapse and maintenance after prediabetes remission are lacking.In the multicenter Prediabetes Lifestyle Intervention Study (n=1105), people with prediabetes underwent 12 months of lifestyle intervention (LI) with deep phenotyping including OGTT-derived insulin sensitivity (IS) and beta cell function (BCF), liver fat content (1H-MRS) and whole-body fat distribution (MRI), before and after LI, and at follow-up. We analyzed data from individuals that achieved prediabetes remission (according to ADA criteria) during LI and had 1-year follow-up data. Relapsers (R) returned to the prediabetic condition at follow-up, while Maintainers (M) remained in remission. Cross-sectional comparisons were made using Wilcoxon tests and longitudinal data were analyzed using mixed effects models adjusting for age and sex (for BMI), plus BMI (for IHL, VAT, IS, BCF).A total of 616 individuals had data at 1-year follow-up and 186 (30 %) achieved remission. Of those, 87 were R and 99 M. At the end of the LI, R had comparable BMI (29.6 kg/m2±5.6 vs 28.3±5.1, p=0.11) and VAT (4.4 l ±2.3 vs 3.7±1.9, p=0.12) but higher IHL (5.7±4.8 vs 3.4±3.9, p=0.019) than M. During follow-up, BMI and IHL trajectories were similar between R and M (p[group over time]=0.43, p=0.60) but VAT increased moderately more in R (p[group over time]=0.05). IS decreased in R but not M (Oral glucose insulin sensitivity index: 381±52 to 333±54 vs 411±51 to 402±58, p