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

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.

 

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Interessenkonflikt

M.R. received lecture fees or served on advisory boards for AstraZeneca, Echosens, Eli Lilly, Madrigal, Merck-MSD, Novo Nordisk and Target RWE and performed investigator-initiated research with support from Boehringer Ingelheim, Novo Nordisk and Nutricia/Danone to the German Diabetes Center (DDZ).

Publikationsverlauf

Artikel online veröffentlicht:
28. Mai 2025