Carbamylated HDL and Mortality Outcomes in Type 2 Diabetes

Abstract

OBJECTIVE: Carbamylation is part of the aging process and causes adverse changes in the structure and function of proteins. Lipoproteins are subjected to carbamylation. We investigated the usefulness of carbamylated HDL as a prognostic indicator of survival in patients with type 2 diabetes and the association with mortality outcomes. RESEARCH DESIGN AND METHODS: Baseline plasma carbamylated HDL was measured by ELISA in a cohort of 1,517 patients with type 2 diabetes. The primary outcome was all-cause mortality, and the secondary outcomes were cause-specific deaths, including cardiovascular, renal, infection, and cancer related. RESULTS: Over a median follow-up of 14 years, 292 patients died, and the mortality rate was 14.5 per 1,000 person-years. Plasma carbamylated HDL level was higher in those with a fatal outcome (46.1 ± 17.8 µg/mL vs. 32.9 ± 10.7; P < 0.01). Patients in the third (hazard ratio [HR] 2.11; 95% CI 1.40-3.17; P < 0.001) and fourth quartiles (HR 6.55; 95% CI 4.67-9.77; P < 0.001) of carbamylated HDL had increased mortality risk. After adjustment for conventional risk factors, elevated carbamylated HDL was independently associated with all-cause mortality (HR 1.39; 95% CI 1.28-1.52; P < 0.001) as well as with all the cause-specific mortalities. Adding plasma carbamylated HDL level improved the power of the multivariable models for predicting all-cause mortality, with significant increments in C index (from 0.78 to 0.80; P < 0.001), net reclassification index, and integrated discrimination improvement. CONCLUSIONS: Carbamylation of HDL renders HDL dysfunctional, and carbamylated HDL is independently associated with mortality outcomes in patients with type 2 diabetes.