Carbamylated HDL and all-cause mortality in type 2 diabetes

Abstract

Background and aims: Carbamylation, a process of post-translational modification of proteins, causes alterations in the structural and functional properties of proteins and contributes to the progression of chronic diseases like renal and cardiovascular disorders. Although carbamylation is previously considered only quantitatively important in uremic conditions, recent studies have shown that carbamylation of proteins can take place even in the absence of uremia by an alternative mechanism mediated by myeloperoxidase. We have previously shown that lipoproteins are subjected to carbamylation in diabetes and carbamylated HDL (cHDL) is dysfunctional. We aim to evaluate whether cHDL is associated with all-cause mortality in patients with type 2 diabetes. Materials and methods: Plasma cHDL concentration was measured in the baseline samples of 990 type 2 diabetic patients followed up in a teaching hospital specialist diabetes clinic by an in-house sandwich ELISA using polyclonal rabbit anti-human cHDL antibody. All-cause mortality was ascertained from hospital electronic medical records. Results: During a mean follow-up of 14 years, 102 subjects died from all causes. Baseline plasma cHDL levels were significantly higher in subjects with a fatal outcome (45.7 ± 19.6 ug/ml versus 35.6 ± 16.3, p<0.01) whereas there were no significant differences in HDL-cholesterol levels (1.17 ± 0.30 mmol/l versus 1.22 ± 0.33 respectively). Plasma cHDL was a significant independent predictor of all-cause mortality even after adjustment for age, gender, body mass index, duration of diabetes, smoking, systolic blood pressure, HbA1c, LDL-cholesterol, cardiovascular disease and lipid lowering therapy at baseline (p<0.001, odds ratio 1.027, 95% CI 1.016 - 1.038). Conclusion: Elevated plasma cHDL was independently associated with all-cause mortality in patients with type 2 diabetes, and cHDL may play a pathological role and contributes to the adverse outcome.