732-P: Biomarkers of Inflammation and Long-Term Microvasculature Integrity in Weight Loss–Induced Prediabetes Remission
Authors: SANDFORTH ARVID , KATZENSTEIN SARAH , SEISSLER JOCHEN , BORNSTEIN STEFAN R. , PERAKAKIS NIKOLAOS , KABISCH STEFAN , PFEIFFER ANDREAS F. , HÄRING HANS-ULRICH , BLÜHER MATTHIAS , SZENDROEDI JULIA , MEYHÖFER SEBASTIAN M. , RODEN MICHAEL , FRITSCHE LOUISE , STEFAN NORBERT , WAGNER ROBERT , FRITSCHE ANDREAS , JUMPERTZ VON SCHWARTZENBERG REINER , BIRKENFELD ANDREAS L. 
Published: June 2023

The Diabetes Prevention Program Outcomes Study demonstrated that even temporary resolution of prediabetes (remission) to normal glucose regulation (NGR) prevents development of T2D and vascular complications. However, cellular mechanisms are unknown. We have previously shown in the Prediabetes Lifestyle Intervention Study, a German Center for Diabetes Research multicenter study (n = 1105), that lifestyle intervention (LI)-mediated weight loss-induced remission of prediabetes to NGR vs. non-remission is largely driven by improved insulin sensitivity. We hypothesized that these two groups differ by markers of chronic low-grade inflammation. Therefore, we analyzed 31 cytokines implicated in energy metabolism and T2D complications before and after LI in subjects losing ≥5% body weight (n = 113) to compare responders achieving NGR (R, n = 40) to non-responders not achieving NGR (NR, n = 73). Cytokines linked to insulin resistance and T2D such as TNF-α (p = 0.73), IFNγ (p = 0.45) and IL-6 (p = 0.34) did not differ between groups. However, responders showed a significantly stronger reduction of lymphotoxin α (LTα, -0.15 ± 0.29-fold in NR vs. -0.23 ± 0.32 in R, p = 0.02). VCAM (-0.04 ± 0.14 NR vs. -0.08 ±10.9 R, p = 0.02) and ICAM (-0.11 ±0.15 NR vs. -0.16 ± 0.14 R, p = 0.02), which are induced by LTα and have been implied in mediating cardiovascular complications, were also more strongly reduced in responders. To assess if this is linked with long-term microvasculature integrity, we applied optoacoustic mesoscopy up to 5 years after LI (n = 22). Total vessel and junction density and number of junction to endpoint branches (NJEB) were higher in responders at follow-up (NJEB: 154.9 ± 25.3 vs. 186.9 ± 16.1, p &lt; 0.01). These data describe a distinct pattern of reduced low-grade inflammation characterizing remission of prediabetes to NGR. Although limited by low n, this pattern may help explain the positive effects of prediabetes remission on vascular complications.

Disclosure
A.Sandforth: None. J.Szendroedi: None. S.M.Meyhöfer: Speaker's Bureau; Novo Nordisk, AstraZeneca, Lilly, Amgen Inc., Boehringer-Ingelheim, Novartis. M.Roden: Advisory Panel; Eli Lilly and Company, Consultant; TARGET PharmaSolutions, Inc., Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis, Sanofi. L.Fritsche: None. N.Stefan: Advisory Panel; Pfizer Inc., Research Support; Sanofi, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Lilly Diabetes, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. R.Wagner: Advisory Panel; Daiichi Sankyo, Speaker's Bureau; Novo Nordisk, Sanofi. A.Fritsche: Advisory Panel; Novo Nordisk, Lilly, Sanofi, Boehringer-Ingelheim, Speaker's Bureau; AstraZeneca, SYNLAB Holding Deutschland GmbH. R.Jumpertz von schwartzenberg: Other Relationship; Sanofi, Amgen Inc., Lilly, Novo Nordisk. A.L.Birkenfeld: None. S.Katzenstein: None. J.Seissler: None. S.R.Bornstein: None. N.Perakakis: Advisory Panel; Bayer Inc., Other Relationship; Novo Nordisk, Novo Nordisk. S.Kabisch: Other Relationship; Berlin-Chemie AG, Sanofi, Lilly, Boehringer Ingelheim Inc., JuZo Akademie, Research Support; J. Rettenmaier / Söhne, Wilhelm-Doerenkamp Foundation, German Center of Diabetes Research. A.F.Pfeiffer: Advisory Panel; Abbott Diabetes, Speaker's Bureau; Novo Nordisk, Sanofi-Aventis Deutschland GmbH. H.Häring: None. M.Blüher: Advisory Panel; Boehringer Ingelheim Inc., Lilly, Novo Nordisk, Consultant; Novo Nordisk Foundation, Speaker's Bureau; Amgen Inc., AstraZeneca, Bayer Inc., Daiichi Sankyo, Novartis, Sanofi-Aventis Deutschland GmbH.