71-OR: Rates of Remission and Metabolic Responses in Data-Driven High-Risk Prediabetes Clusters
Authors: KATZENSTEIN SARAH , SANDFORTH ARVID , MINELLI FAIAO VITORIA , SANDFORTH LEONTINE , SCHICK FRITZ , MACHANN JÜRGEN , PETER ANDREAS , SEISSLER JOCHEN , PERAKAKIS NIKOLAOS , SCHÜRMANN ANNETTE , PFEIFFER ANDREAS F. , KABISCH STEFAN , BLÜHER MATTHIAS , SZENDROEDI JULIA , SOLIMENA MICHELE , BORNSTEIN STEFAN R. , FRITSCHE ANDREAS , WAGNER ROBERT , RODEN MICHAEL , STEFAN NORBERT , JUMPERTZ VON SCHWARTZENBERG REINER , BIRKENFELD ANDREAS L. 
Published: June 2024

We have previously shown that weight loss-induced remission of prediabetes is mediated by improved insulin sensitivity (IS) and characterized by reduced visceral adipose tissue mass (VAT). Remission markedly reduces the risk for type 2 diabetes. We hypothesized that patients from specific high-risk Tübingen Prediabetes Clusters show a reduced remission response to a lifestyle intervention (LI). 707 individuals with prediabetes from the Prediabetes Lifestyle Intervention Study before and after 12 months of LI were categorized into 3 high-risk clusters: C3 (n=334), C5 (n=188), C6 (n=185). C3 and C5 have a high risk for T2D and complications, C6 for complications only. Remission was defined by normal glucose regulation (ADA standards). Deep phenotyping included OGTT derived IS and insulin secretion (InSec), liver fat content (1H-MRS) and whole-body fat distribution (MRI). Mixed effects models were applied comparing participants going into remission (R) vs those with no remission (NR). At the end of the LI, remission rates were lowest in C5 compared to C3 and C6 (C3: 21% vs C5: 16% vs C6: 36%, p&lt;0.001), despite highest weight (C3: -3.3±5.4% vs C5: -4.8±6.4 vs C6: -3.8±5.2, p&lt;0.001) and liver fat reduction (C3: -1.8±3.4% vs C5: -8.1±7.7 vs C6: -3.0±4.2 and; p&lt;0.0001). Within all clusters, IS increased more in R vs NR (OGIS (ml/min/m2); C3: R +72±56 vs NR +18±49; C5: +98±80 vs +26±58; C6: +56±52 vs +21±53, each p&lt;0.001). In C3 InSec increased more in R vs NR (AUCC-PEP0-30/AUCGluc0-30); R +6.7±34.7 vs NR +2.6±30.5, p=0.006), but it decreased in C6 NR (R -2.9±50.4 vs NR -14.5±46.3, p=0.007). In C5, which had the lowest remission rate, InSec did not differ between R and NR (R -22.9±53.7 vs NR -1.1±39.2, p=0.337). These data identify a precise subgroup of patients with prediabetes, C5, who are less likely to achieve remission in response to LI than patients from other high-risk Tübingen Prediabetes Clusters, despite the strongest weight loss. Patients in this subgroup require more precise preventive strategies.

Disclosure
S. Katzenstein: None. A. Sandforth: None. V. Minelli Faiao: None. L. Sandforth: None. F. Schick: None. J. Machann: None. A. Peter: None. J. Seissler: None. N. Perakakis: Advisory Panel; Bayer Inc. Other Relationship; Lilly Diabetes, Novo Nordisk. A. Schürmann: None. A.F. Pfeiffer: Advisory Panel; Abbott. Speaker's Bureau; AstraZeneca, Novo Nordisk, Sanofi. Advisory Panel; Berlin-Chemie AG. 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. 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. J. Szendroedi: None. M. Solimena: None. S.R. Bornstein: None. A. Fritsche: Speaker's Bureau; Novo Nordisk, Sanofi-Aventis Deutschland GmbH, SYNLAB Holding Deutschland GmbH. R. Wagner: Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk. 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. R. Jumpertz von Schwartzenberg: None. A.L. Birkenfeld: None.