Phenotype-based clusters, inflammation and complications in older people before the diagnosis of type 2 diabetes: KORA F4/FF4 cohort study

M T Huemer; M C Spagnuolo; H Maalmi; R Wagner; G J Bönhof; M Heier; W Koenig; W Rathmann; K Prystupa; J Nano; D Ziegler; A Peters; M Roden; B Thorand; C Herder

doi:10.1055/s-0045-1807406

Diabetologie und Stoffwechsel, Table of Contents

Diabetologie und Stoffwechsel 2025; 20(S 01): S27
DOI: 10.1055/s-0045-1807406

Abstracts | DDG 2025

Poster

Posterwalk 2: Klinische Diabetologie Typ-2 Diabetes

Phenotype-based clusters, inflammation and complications in older people before the diagnosis of type 2 diabetes: KORA F4/FF4 cohort study

M T Huemer

¹Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany

,

M C Spagnuolo

²German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Institute for Clinical Diabetology, Düsseldorf, Germany

,

H Maalmi

²German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Institute for Clinical Diabetology, Düsseldorf, Germany

,

R Wagner

³Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Department of Endocrinology and Diabetology, Düsseldorf, Germany

,

G J Bönhof

³Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Department of Endocrinology and Diabetology, Düsseldorf, Germany

,

M Heier

⁴University Hospital Augsburg, KORA Study Centre, Augsburg, Germany

,

W Koenig

⁵TUM University Hospital, German Heart Centre, München, Germany

,

W Rathmann

⁶German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Institute for Biometrics and Epidemiology, Düsseldorf, Germany

,

K Prystupa

²German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Institute for Clinical Diabetology, Düsseldorf, Germany

,

J Nano

¹Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany

,

D Ziegler

²German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Institute for Clinical Diabetology, Düsseldorf, Germany

,

A Peters

¹Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany

,

M Roden

³Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Department of Endocrinology and Diabetology, Düsseldorf, Germany

,

B Thorand

¹Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany

,

C Herder

²German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Institute for Clinical Diabetology, Düsseldorf, Germany

› Author Affiliations

Abstract

Full Text

Aim: Using a data-driven approach, six clusters with different risk profiles and burden of complications were recently identified in middle-aged people before the diagnosis of type 2 diabetes (T2D). We aimed to investigate whether these clusters could be generalised to older people and if subclinical inflammation was related to their cardiometabolic risk profiles.

Methods: We assigned 843 participants of the KORA F4 study aged 61-82 years without T2D to the six previously defined phenotype-based clusters. Based on 73 protein biomarkers of subclinical inflammation, we derived an inflammation-related score (“inflammatory load”) using principal component analysis to assess subclinical inflammation. Risk factors, inflammatory load as well as prevalence and incidence of (pre)diabetes-related complications were compared between the clusters using pairwise comparisons and regression analyses.

Results: Clusters 1 and 2 had the lowest cardiometabolic risk, whereas clusters 5 and 6 had the highest risk. T2D risk was highest in clusters 3, 4, 5, and 6 compared with the low-risk cluster 2 (age and sex-adjusted ORs between 3.6 and 34.0). In cross-sectional analyses, there were significant between-cluster differences in chronic kidney disease (CKD), distal sensorimotor polyneuropathy (DSPN) and cardiovascular disease (all p<0.045). In prospective analyses (mean follow-up time 6.5-8.3 years), clusters differed significantly in CKD and DSPN incidence, but not in incident CVD or all-cause mortality. The inflammatory load was highest in the high-risk cluster 5 and lowest in the low-risk cluster 2. Adjustment for the inflammatory load had only a minor impact on the aforementioned associations of clusters with outcomes.

Conclusions: Our findings extend the knowledge about the previously identified six phenotype-based clusters in older people without T2D. Differences between clusters were more pronounced for T2D risk than for prevalent or incident (pre)diabetes-related complications and absent for mortality. The high cardiometabolic risk corresponded to the high inflammatory load in cluster 5.