Integr Biol (Camb). 2026 Jan 16;18:zyag019. doi: 10.1093/intbio/zyag019.
ABSTRACT
BACKGROUND: Diabetes mellitus (DM) and its cardiovascular complications represent one of the most prevalent causes of death worldwide, closely linked to chronic inflammatory states. Inflammatory Burden Index (IBI) is a composite inflammatory marker that comprehensively assesses systemic inflammation levels. Currently, the prognostic association of IBI with outcomes in individuals living with DM and prediabetes (pre-DM) remains unclear.
OBJECTIVE: To investigate association of IBI with all-cause and cardiovascular mortalities in individuals living with DM and pre-DM.
METHODS: Utilizing data from NHANES 1999-2010, we enrolled 8738 participants. Kaplan-Meier analysis and weighted multivariate Cox proportional hazards models were employed to examine relationship of IBI tertiles with mortality risk. RCS analysis tested for non-linear associations, while subgroup analyses evaluated effect modification. Sensitivity analysis was performed by excluding deaths occurring during the early follow-up period.
RESULTS: During a median 11.7 years of follow-up, 2726 all-cause deaths (31.2%) and 893 cardiovascular deaths (10.2%) were recorded. Results demonstrated significant associations of IBI with mortality risks in individuals living with pre-DM and DM. In fully adjusted model, compared with the lowest IBI tertile (T1), the highest tertile (T3) was associated with a 42% elevated risk of all-cause mortality (HR = 1.42, 95%CI: 1.24-1.63, P < 0.001) and a 38% elevated risk of cardiovascular mortality (HR = 1.38, 95%CI: 1.08-1.76, P = 0.011). RCS analysis revealed an overall significant association of IBI with mortality risks without evidence of non-linearity (P-non-linear>0.05). No significant interaction effects were seen in subgroup analyses. After excluding deaths occurring within the first 1 and 2 years of follow-up in sensitivity analyses, the above associations remained generally consistent.
CONCLUSION: Elevated IBI was significantly associated with elevated risks of all-cause and cardiovascular mortalities in persons with DM and pre-DM, suggesting that IBI may help identify subjects at higher mortality risk within this population.
HIGHLIGHTS: Elevated inflammatory burden index was significantly associated with increased risks of all-cause and cardiovascular mortality in individuals with diabetes and prediabetes. Insight Box This study identifies the Inflammatory Burden Index as a stable, integrative biomarker linking systemic inflammation to elevated all-cause and cardiovascular mortality in prediabetic and diabetic individuals. By quantifying cumulative inflammatory burden rather than single markers, it provides a biologically coherent, clinically accessible tool for risk stratification. These findings support integrated inflammatory monitoring as a rational strategy to improve prognostic evaluation and targeted intervention in glucose metabolism disorders, bridging molecular inflammation, cardiometabolic pathophysiology, and population-level clinical outcomes.
PMID:42855431 | DOI:10.1093/intbio/zyag019