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.

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).

Publication History

Article published online:
28 May 2025