728-P: Biomarkers of Low-Grade Inflammation in Novel Subtypes of Patients at Risk for Diabetes
Authors: KATZENSTEIN SARAH , SANDFORTH ARVID , MINELLI FAIAO VITORIA , SEISSLER JOCHEN , BORNSTEIN STEFAN R. , PERAKAKIS NIKOLAOS , SCHÜRMANN ANNETTE , KABISCH STEFAN , BLÜHER MATTHIAS , SZENDROEDI JULIA , RODEN MICHAEL , FRITSCHE LOUISE , STEFAN NORBERT , WAGNER ROBERT , FRITSCHE ANDREAS , BIRKENFELD ANDREAS L. , JUMPERTZ VON SCHWARTZENBERG REINER 
Published: June 2023

In the Tübingen Family Study recently 6 subtypes of prediabetic metabolism were identified. Cluster 3, 5 and 6 have a moderate to high risk for T2D or its associated complications. Cluster 3 is characterized by low insulin secretion, cluster 5 by insulin resistance and high liver fat content. Individuals in cluster 6 have an elevated risk of nephropathy despite a delayed diabetes development. Low-grade inflammation has been implicated in the development of T2D and cardiorenal complications. We hypothesized that the subtypes differ in levels of inflammatory biomarkers. Thus, we measured 31 inflammatory biomarkers associated with metabolic disease. We used Bio-Plex® multiplex immunoassays in 145 individuals who were recruited in Tübingen from the Prediabetes Lifestyle Intervention Study (PLIS) - a multicenter study conducted in individuals with ADA-defined prediabetes. Cluster comparison was done using ANOVA models, raw unadjusted values are reported. We identified eight biomarkers which differed among diabetes-risk subtypes, namely MIP1a, MIP1b, IL18, Osteopontin (OPN), IFNy, TNFb, and soluble TNFa-Receptor (sTNF-R)- 1 and -2. High risk cluster 3, 5 and 6 had significantly elevated levels of several inflammatory biomarkers compared to low risk cluster 2 with the lowest levels of these biomarkers. Within the high-risk groups, cluster 5 had increased biomarker levels compared to cluster 3 (e.g., IL-18: cluster 5: 86.2 pg/ml ± 3.9 vs cluster 3: 66.8 pg/ml ± 4.8, p=0.018; OPN: 16.8 ng/ml ± 1.0 vs. 12.8 ng/ml ± 0.8, p = 0.022; MIP1a 2.2 pg/ml ± 0.1 vs. 1.6 pg/ml ± 0.1, p &lt; 0.001). Cluster 6 showed lower levels of IFNy than cluster 3 (2.2pg/ml ± 0.3 vs 3.5pg/ml ± 0.2, P=0.019). Our data show that the novel T2D risk subtypes differ in inflammatory biomarkers. This suggests that a low-grade inflammation may be involved in the progression from prediabetes to T2D and complications. A more precise mechanistic understanding is needed in order to establish precise preventive strategies for different risk phenotypes.

Disclosure
S.Katzenstein: None. J.Szendroedi: None. 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. A.L.Birkenfeld: None. R.Jumpertz von schwartzenberg: Other Relationship; Sanofi, Amgen Inc., Lilly, Novo Nordisk. A.Sandforth: None. V.Minelli faiao: None. J.Seissler: None. S.R.Bornstein: None. N.Perakakis: Advisory Panel; Bayer Inc., Other Relationship; Novo Nordisk, Novo Nordisk. A.Schürmann: None. 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. 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.