Acute inflammation amplifies the diabetogenic effect of excess adiposity: Evidence from a real‐life, prospective cohort

AIMS: Mounting evidence has suggested the probable involvement of infections in obesity-associated type 2 diabetes. This study aims to evaluate the association between acute inflammation and type 2 diabetes risk and to examine whether this association is modified by adiposity status. MATERIALS AND METHODS: . Multivariable Cox regression models estimated diabetes risk, and both multiplicative and additive interactions were evaluated. RESULTS: During a median follow-up of 11 years, 14 189 participants developed diabetes. Both elevated hsCRP and overweight/obesity independently increased diabetes risk. Acute inflammation was associated with a higher diabetes risk [hazard ratio (HR): 1.14; 95% confidence interval (CI): 1.04-1.22], particularly among those with excess adiposity [HR: 1.24 (1.13-1.36)] compared to those with normal weight [HR: 1.00 (0.83-1.21); P-interaction = 0.0112]. A supra-additive interaction was observed (relative excess risk due to interaction: 0.27; 95% CI: 0.02-0.52), with stronger synergistic effects seen in individuals under 60 and differences noted by sex. CONCLUSIONS: Acute inflammation significantly elevates diabetes risk in overweight/obese individuals but not in those with normal weight, highlighting the synergistic role of adiposity and immune activation in diabetes pathogenesis and the importance of weight control in prevention strategies.