Joint association of diabetes mellitus and inflammation status with biological ageing acceleration and premature mortality

Background: We aimed to investigate the associations of diabetes mellitus (DM) and C-reactive protein (CRP) with biological ageing acceleration and mortality risk. Methods: We analyzed data from 41,634 adults with CRP and DM at baseline. Subjects were categorized into high CRP (>3 mg/L) and low CRP (<= 3 <= 3 mg/L) groups. The cross-sectional endpoints of the study were biological ageing indicators Klemera-Doubal method BioAge acceleration (KDMAccel) and Phenotypic age acceleration (PhenoAgeAccel), and the follow-up endpoints were all-cause mortality and cardiovascular mortality. Results: In adults with high CRP, compared with those without DM, PhenoAgeAccel increased by 1.66 years (95 % CI: 1.38-1.93), and 8.74 years (95 % CI: 8.25-9.22) in adults with prediabetes and DM, respectively (p for interaction <0.001). Using the CRPlow/non-DM low /non-DM group as a reference, adults in the CRPhigh/non-DM, high /non-DM, CRPlow/DM, low /DM, and CRPhigh/DM high /DM groups had significantly advanced biological ageing. Compared to adults without DM, low CRP, and no ageing acceleration, the multivariable-adjusted HRs (95%CIs) of all-cause and cardiovascular mortality in those with DM, CRP, and ageing acceleration were 3.22 (2.79-3.72), and 3.57 (2.81-4.54), respectively. Conclusions: These findings suggest that the joint presence of low-grade inflammation and DM might be associated with higher odds of biological ageing acceleration and premature mortality.