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

CONTEXT 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. OBJECTIVE We investigated whether REMAP associates with and improves the prediction of mortality in type 2 diabetes. DESIGN 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. RESULTS 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). CONCLUSIONS 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.