Low-grade inflammation predicts major cardiovascular events and mortality in recently diagnosed type 2 diabetes: A Danish nationwide cohort study

Aims This study aimed to investigate the prospective associations of interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hsCRP) levels with major adverse cardiac event (MACE) and mortality in individuals recently diagnosed with type 2 diabetes and without prevalent CVD. Methods We included 7630 individuals recently diagnosed with type 2 diabetes (median duration 0.9 years) with a median age of 60 years (44% females). Individuals with prevalent CVD (n=1390) were excluded from the primary analyses modelling Fine-Gray subdistribution hazard regressions accounting for competing risk of non-CVD death and adjusting for classical risk factors (e.g. diabetes duration, smoking, alcohol, physical activity, waist circumference, LDL cholesterol, HbA1c, systolic blood pressure, eGFR, and pharmacological treatment). Subsequently, we evaluated the predictive ability of adding low-grade inflammation to a model containing classical risk factors. Results Median follow-up time was 9 years. A 1-SD increase in log-IL-6 (1.98 pg/mL), log-TNF-α (1.40 pg/mL) and log-hsCRP (3.28 mg/L) was associated with HRs of 1.16 (95% CI 1.09, 1.23), 1.01 (0.95, 1.08), and 1.16 (1.09, 1.25) for MACE and 1.38 (1.31, 1.45), 1.16 (1.10, 1.22), and 1.34 (1.25, 1.43) for all-cause mortality, respectively. Prediction of both MACE and all-cause mortality was slightly improved by adding IL-6 and hsCRP to the model alongside classical risk factor. Conclusions Low-grade inflammation was associated with MACE and all-cause mortality, independently of classical risk factors, in individuals recently diagnosed with type 2 diabetes and without prevalent CVD. Despite improved predictive ability of IL-6 and hsCRP, the absolute improvement was sparse.