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 HbA1c (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 HbA1c. The magnitude of reduction in plasma cLDL correlated with changes in MPO, but not with HbA1c 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.
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Research Article|
September 23 2013
Carbamylation of LDL and its relationship with myeloperoxidase in Type 2 diabetes mellitus
Sammy W. M. Shiu;
Sammy W. M. Shiu
1
*Department of Medicine, University of Hong Kong, Hong Kong
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Su-Mei Xiao;
Su-Mei Xiao
1
*Department of Medicine, University of Hong Kong, Hong Kong
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Ying Wong;
Ying Wong
*Department of Medicine, University of Hong Kong, Hong Kong
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Wing-Sun Chow;
Wing-Sun Chow
*Department of Medicine, University of Hong Kong, Hong Kong
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Karen S. L. Lam;
Karen S. L. Lam
*Department of Medicine, University of Hong Kong, Hong Kong
†Research Center of Heart, Brain, Hormone and Healthy Aging, University of Hong Kong, Hong Kong
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Kathryn C.B. Tan
*Department of Medicine, University of Hong Kong, Hong Kong
†Research Center of Heart, Brain, Hormone and Healthy Aging, University of Hong Kong, Hong Kong
Correspondence: Professor Kathryn C.B. Tan (email kcbtan@hkucc.hku.hk).
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Clin Sci (Lond) (2014) 126 (2): 175–181.
Article history
Received:
July 08 2013
Revision Received:
July 29 2013
Accepted:
August 01 2013
Accepted Manuscript online:
August 01 2013
Citation
Sammy W. M. Shiu, Su-Mei Xiao, Ying Wong, Wing-Sun Chow, Karen S. L. Lam, Kathryn C.B. Tan; Carbamylation of LDL and its relationship with myeloperoxidase in Type 2 diabetes mellitus. Clin Sci (Lond) 1 January 2014; 126 (2): 175–181. doi: https://doi.org/10.1042/CS20130369
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