Is glycation of low density lipoproteins in patients with Type 2 diabetes mellitus a LDL pre-oxidative condition?
OBJECTIVE
The study aimed to evaluate whether low density lipoprotein (LDL) in diabetic patients is more glycated and susceptible to oxidation than in non-diabetic subjects and investigated the hypothesis that LDL glycation is associated with an increased plasma concentration of LDL- (a circulating electronegatively charged LDL), proposed as an index of in vivo oxidation.


METHODS
LDL glycation was measured by a competitive enzyme immunoadsorbent assay, using a monoclonal antibody against glycated apoB in 24 Type 2 diabetic patients and 12 healthy controls. LDL- was separated by ion-exchange HPLC in LDL samples obtained after sequential preparative ultracentrifugation (density range 1.019-1.063). In vitro LDL susceptibility to oxidation was evaluated by following the kinetics of conjugated diene formation and by measuring the lag-phase time in the presence of copper (Cu2+) ions.


RESULTS
The percentages of glycated apoB (3.33+/-2.54% vs. 1.24+/-0.71%) and of LDL- (3.88+/-1.49% vs. 2.34+/-1.03%) in total LDL were significantly higher in diabetic patients (P<0.01 for both). LDL- was positively correlated with glycated apoB (r = 0.68, P<0.001). LDL isolated from Type 2 diabetic patients showed a significant decrease (P<0.001) in the resistance to oxidative stress, as indicated by the shorter lag-phase time (91+/-12.6 vs. 120+/-24.5 min). The lag-phase time was inversely correlated with glycated apoB (r = -0.65, P<0.001) and LDL- concentrations (r = -0.69, P<0.001).


CONCLUSIONS
In this population of Type 2 diabetic patients, LDL were more glycated, more susceptible to in vitro oxidation and had a higher percentage of electronegative LDL. The glycation of apoB is proposed to be associated with a significative increase of in vivo and in vitro LDL oxidation.
Moro
E
E
2nd Department of Internal Medicine and Metabolic Diseases, Venice General Hospital, Italy.
Alessandrini
P
P
Zambon
C
C
Pianetti
S
S
Pais
M
M
Cazzolato
G
G
Bon
G B
GB
D000368:Aged; D000911:Antibodies, Monoclonal; D001055:Apolipoproteins B / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D019270:Fructosamine / Q000097:blood; D006442:Glycated Hemoglobin / Q000032:analysis; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D012016:Reference Values; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood; D014810:Vitamin E / Q000097:blood; D000093844:Glycated Proteins
D000911:Antibodies, Monoclonal; D001055:Apolipoproteins B; D015415:Biomarkers; D002784:Cholesterol; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019270:Fructosamine; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; D008315:Malondialdehyde; D014280:Triglycerides; D014810:Vitamin E; C031797:glycated lipoproteins, LDL; D000093844:Glycated Proteins