1325-P: Continuous Representation of Type 2 Diabetes Heterogeneity on a Tree-Like Graph Structure Stratifies Risk of Complications
Authors: SCHÖN MARTIN , PRYSTUPA KATSIARYNA , MORI TIM , ZAHARIA OANA P. , BÓDIS KÁLMÁN , KUPRIYANOVA YULIYA , NAIR ANAND , STROM ALEXANDER , GUTHOFF RAINER , BÖNHOF GIDON J. , BIRKENFELD ANDREAS L. , SEISSLER JOCHEN , PFEIFFER ANDREAS F. , BLÜHER MATTHIAS , BORNSTEIN STEFAN R. , SZENDROEDI JULIA , MEYHOEFER SVENJA , BURKART VOLKER , SCHRAUWEN-HINDERLING VERA , KUSS OLIVER , PEARSON EWAN , RODEN MICHAEL , WAGNER ROBERT ,   THE GERMAN DIABETES STUDY (GDS) GROUP
Published: June 2023

Heterogeneity in type 2 diabetes (T2D) can be represented by a tree-like structure using reverse graph-embedded dimensionality reduction. We aimed to validate this approach and study if intensified phenotyping stratifies complications. Participants (n=927) of the German Diabetes Study (GDS) with recent-onset T2D were mapped onto a two-dimensional tree based on HbA1c, BMI, total and HDL cholesterol, triglycerides, alanine aminotransferase, creatinine, systolic and diastolic blood pressure, residualized for age and sex. A subset (n=447) had follow-up examinations after 5 years. Phenotypic variability rendered on a tree structure showed gradients for insulin sensitivity (hyperinsulinemic-euglycemic clamp, both dimensions: p&lt;0.001) and insulin secretion (intravenous glucose tolerance test, both dimensions: p&lt;0.001) (Fig 1). Individuals in the tree branch with the lowest insulin sensitivity had the highest liver fat content (1H-MR spectroscopy, pdim1&lt;0.001, pdim2=0.04), elevated cardiovascular hazard (nevents=147, HRmax 4.0, pdim1=0.2, pdim2&lt;0.001) and diabetic retinopathy (nevents=36, fundus photography, HRmax 2.5, pdim1=0.04, pdim2=0.2). This method provides an alternative approach to discrete clusters in identifying persons at high risk of certain diabetes-related diseases, potentially providing a framework for precision diabetology.

Disclosure
M.Schön: None. G.J.Bönhof: None. A.L.Birkenfeld: None. J.Seissler: None. A.F.Pfeiffer: Advisory Panel; Abbott Diabetes, Speaker's Bureau; Novo Nordisk, Sanofi-Aventis Deutschland GmbH. 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. S.R.Bornstein: None. J.Szendroedi: None. S.Meyhoefer: None. V.Burkart: None. V.Schrauwen-hinderling: None. K.Prystupa: Other Relationship; Berlin-Chemie AG. O.Kuss: Consultant; Berlin-Chemie AG. E.Pearson: Speaker's Bureau; Novo Nordisk, Lilly, Illumina. M.Roden: Advisory Panel; Eli Lilly and Company, Consultant; TARGET PharmaSolutions, Inc., Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis, Sanofi. R.Wagner: Advisory Panel; Daiichi Sankyo, Speaker's Bureau; Novo Nordisk, Sanofi. The german diabetes study (gds) group: n/a. T.Mori: None. O.P.Zaharia: None. K.Bódis: None. Y.Kupriyanova: None. A.Nair: None. A.Strom: None. R.Guthoff: Other Relationship; Alimera, Bayer Inc., Novartis, Allergan.

Funding
German Diabetes Center; German Federal Ministry of Health (Berlin, Germany); Ministry of Culture and Science of the state North Rhine-Westphalia (Düsseldorf, Germany); German Federal Ministry of Education and Research; German Center for Diabetes Research