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

BACKGROUND: 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 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 the highest. 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 cluster 2. Adjustment for the inflammatory load had only a minor impact on the aforementioned differences in outcomes between clusters.

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 but not to the lower inflammatory load of high-risk clusters 3 and 6.