OR05-2 Carbamylation of LDL in Type 2 Diabetes Mellitus

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR05-Lipids: Regulation & Mechanism of Disease
Saturday, June 15, 2013: 11:30 AM-1:00 PM
Presentation Start Time: 11:45 AM
Room 133 (Moscone Center)
Kathryn CB Tan*, Joanne KY Lam, Sammy WM Shiu and Ying Wong
University of Hong Kong, Hong Kong
Several proatherogenic modifications of LDL have been detected in humans. In addition to oxidative modification, LDL is also subjected to post-translational protein modification like carbamylation in vivo. Carbamylation is a spontaneous non-enzymatic modification of lysine or the terminal protein amino acids of apolipoprotein B by urea-derived isocyanate, and carbamylated LDL (cLDL) is an important proatherogenic isoform of LDL in conditions like uraemia. Recent evidence has shown that cLDL is also found in healthy individuals and can be formed by urea-independent mechanism. The objective was to investigate plasma cLDL level in type 2 diabetes and its association with myeloperoxidase (MPO) which can catalyse protein carbamylation. 

264 diabetic patients not on lipid lowering agents and 200 non-diabetic controls were recruited. Plasma cLDL concentration was measured using an in-house sandwich ELISA using polyclonal rabbit anti-human cLDL antibody. Plasma MPO and high sensitivity C-reactive protein (CRP) was measured by ELISA and immunoturbidimetric assay respectively. 

Plasma LDL cholesterol and apolipoprotein B levels were similar between diabetic patients and controls. However, plasma cLDL level was higher in diabetic subjects than controls [327.6 ng/mg (231.0 – 501.8) vs 302.4 ng/mg (215.6 – 425.6) respectively, median (interquartile range), p<0.01], and this remained significant even after excluding subjects with elevated urea level. Both plasma MPO and CRP were also significantly increased in diabetic subjects (p<0.01). Plasma cLDL correlated with plasma MPO (r=0.40, p<0.001) and urea (r=0.23, p<0.01) but not with CRP in diabetic subjects. On linear regression analysis, plasma MPO remained an independent determinant of plasma cLDL even after adjusting for age, gender, body mass index, HbA1c and urea (partial correlation r=0.31, p<0.001) in subjects with diabetes.

In conclusion, plasma level of cLDL is increased in patients with type 2 diabetes and is partly related to MPO-induced carbamylation. Carbamylated LDL is pro-atherogenic and may contribute to the increased cardiovascular risk of diabetic subjects.

Nothing to Disclose: KCT, JKL, SWS, YW

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Supported by HKU CRCG grant.