721-P: Mechanisms of Relapse after Lifestyle Intervention–Induced Remission of Prediabetes
Authors: SANDFORTH ARVID , SANDFORTH LEONTINE , KATZENSTEIN SARAH , SEISSLER JOCHEN , PERAKAKIS NIKOLAOS , WAGNER ROBERT , MACHANN JÜRGEN , SCHICK FRITZ , PETER ANDREAS , PREISSL HUBERT , SZENDROEDI JULIA , SOLIMENA MICHELE , BLÜHER MATTHIAS , SCHÜRMANN ANNETTE , KABISCH STEFAN , PFEIFFER ANDREAS F. , BORNSTEIN STEFAN R. , RODEN MICHAEL , STEFAN NORBERT , FRITSCHE ANDREAS , BIRKENFELD ANDREAS L. , JUMPERTZ VON SCHWARTZENBERG REINER , WORKING GROUP PLIS 
Published: June 2024

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&lt;0.001) as well as BCF (Adaptation Index: 65296±23089 to 52256±16970 vs 63442±28700 to 63718±24284, p&lt;0.001).Relapse after remission from prediabetes is characterized by increased VAT and is driven by declining IS and BCF, highlighting important differences to relapse from T2D remission. Our data suggest that strategies to prevent relapse from remission of prediabetes after a lifestyle intervention need to target both, IS and BCF.

Disclosure
A. Sandforth: None. L. Sandforth: None. S. Katzenstein: None. J. Seissler: None. N. Perakakis: Advisory Panel; Bayer Inc. Other Relationship; Lilly Diabetes, Novo Nordisk. R. Wagner: Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk. J. Machann: None. F. Schick: None. A. Peter: None. H. Preissl: None. J. Szendroedi: None. M. Solimena: None. M. Blüher: Speaker's Bureau; Amgen Inc., AstraZeneca, Bayer Inc., Daiichi Sankyo. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Novartis AG. Advisory Panel; Novo Nordisk. Speaker's Bureau; Pfizer Inc., Sanofi. A. Schürmann: None. S. Kabisch: Other Relationship; Sanofi, Boehringer-Ingelheim, Berlin-Chemie AG. Research Support; J. Rettenmaier & Söhne, Rosenberg, Germany, California Walnut Commission, Almond Board of California, Wilhelm-Doerenkamp-Foundation. Other Relationship; JuZo-Akademie, Lilly Diabetes. A.F. Pfeiffer: Advisory Panel; Abbott. Speaker's Bureau; AstraZeneca, Novo Nordisk, Sanofi. Advisory Panel; Berlin-Chemie AG. S.R. Bornstein: None. M. Roden: Advisory Panel; Eli Lilly and Company. Research Support; Boehringer-Ingelheim. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc. Speaker's Bureau; AstraZeneca. N. Stefan: Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Lilly Diabetes, MSD Life Science Foundation, Novo Nordisk. Advisory Panel; Pfizer Inc. Research Support; Sanofi-Aventis Deutschland GmbH. Advisory Panel; GlaxoSmithKline plc. A. Fritsche: Speaker's Bureau; Novo Nordisk, Sanofi-Aventis Deutschland GmbH, SYNLAB Holding Deutschland GmbH. A.L. Birkenfeld: None. R. Jumpertz von Schwartzenberg: None.