A serum resistin and multi-cytokine inflammatory pathway is linked with and helps predict all-cause death in diabetes.

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Type 2 diabetes shows high mortality rate, partly mediated by atherosclerotic plaque instability. Discovering novel biomarkers may help identify high-risk patients to expose to more aggressive and specific managements. We recently described a serum REsistin and multiMulti-cytokine inflammAatory Pathway (REMAP), including resistin, IL-1β, IL-6, IL-8 and TNF-α) which associates with cardiovascular disease.We investigated whether REMAP associates with and improves the prediction of mortality in type 2 diabetes.A REMAP score was investigated in three cohorts comprising 1,528 patients with T2D (409 incident deaths) and in 59 patients who underwent carotid endoarterectomy (CEA; 24 deaths). Plaques were classified as unstable/stable according to the modified American Heart Association atherosclerosis classification.REMAP was associated to all-cause mortality in each cohort and in all 1,528 individuals (fully-adjusted HR for one SD increase =1.34, p<0.001). In CEA patients, REMAP was associated with mortality (HR =1.64, p = 0.04) and a modest change was observed when plaque stability was taken into account [HR =1.58; P = 0.07]. REMAP improved discrimination and reclassification measures of both ENFORCE and RECODe, well-established prediction models of mortality in type 2 diabetes (P<0.05-<0.001).REMAP is independently associated with and improves predict all-cause mortality in type 2 diabetes; it can therefore be used to identify high-risk individuals to be targeted with more aggressive managements. Whether REMAP can also identify those patients who are more responsive to IL-6 and IL-1β monoclonal antibodies which reduce cardiovascular burden and total mortality is an intriguing possibility to be tested.

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Authors: Maria Giovanna Scarale, Alessandra Antonucci, Marina Cardellini, Massimiliano Copetti, Lucia Salvemini, Rossella Menghini, Tommaso Mazza, Viviana Casagrande, Gianluigi Ferrazza, Olga Lamacchia, Salvatore De Cosmo, Rosa Di Paola, Massimo Federici, Vincenzo Trischitta, Claudia Menzaghi