Carbamylation of LDL and its relationship with myeloperoxidase in Type 2 diabetes mellitus

LDL (low-density lipoprotein) is subjected to pro-atherogenic modifications in the circulation. A novel uraemia-independent mechanism of carbamylation of lipoproteins mediated by MPO (myeloperoxidase) has recently been reported. We have investigated whether carbamylation of LDL was increased in patients with Type 2 diabetes without renal impairment and the role of MPO. cLDL (carbamylated LDL) and MPO were measured by ELISA in a cross-sectional study of 198 patients and 174 non-diabetic controls. The impact of lowering MPO on plasma cLDL was determined by assaying cLDL and MPO in archived samples from a previous randomized open-label parallel group study comparing rosiglitazone (n=20) and sulfonylurea (n=24). Both plasma cLDL (P<0.05) and MPO levels (P<0.01) were higher in patients with Type 2 diabetes than controls in the cross-sectional study. Plasma cLDL correlated with MPO (r=0.42 and P<0.01) in subjects with diabetes, and plasma MPO was an independent determinant of plasma cLDL even after adjusting for age, gender, BMI (body mass index), apoB (apolipoprotein B), urea and HbA_1c (glycated haemoglobin). In the randomized trial, rosiglitazone significantly lowered MPO (P<0.01) and cLDL (P<0.05), whereas no changes were observed in the sulfonylurea group despite a similar reduction in HbA_1c. The magnitude of reduction in plasma cLDL correlated with changes in MPO, but not with HbA_1c in the rosiglitazone group, suggesting that lowering MPO reduced plasma cLDL. Plasma cLDL is increased in patients with Type 2 diabetes even in the absence of renal impairment and carbamylation of LDL in these subjects is mainly mediated by MPO and not by urea.