LDL oxidative modifications in well- or moderately controlled type 2 diabetes.
BACKGROUND
The aim of the study was to examine, by measurement of specific indicators of free radical-mediated oxidation of LDL, whether there is evidence of increased in vivo oxidation of LDL in type 2 diabetic patients, and to investigate their associations with carotid intima media thickness (IMT).


METHODS
In native LDL, we quantified five different products of LDL oxidation reflecting various stages of LDL oxidative modification in 38 individuals with well- or moderately controlled type 2 diabetes (HbA(1c) </= 8.5%) and 38 gender-matched subjects with normal glucose metabolism. Baseline conjugated dienes (BCD), 7-OH-glycero-phosphocholine (7-OH-GPC), lyso-phosphatidylcholine (lyso-PC), and ketocholesterol were determined in LDL, and circulating in vivo oxidized apolipoprotein B100 (Ox-apoB) was measured in plasma. The IMT of the carotid artery was measured by ultrasound.


RESULTS
Borderline higher carotid IMT values were observed in individuals with diabetes (0.88 +/- 0.14 vs 0.83 +/- 0.11 mm, p = 0.06). LDL-ketocholesterol (45.5 +/- 19.4 vs 37.1 +/- 13.8 nmol/mmol LDL-cholesterol, p < 0.05) and Ox-apoB (25.3 +/- 5.5 vs 22.2 +/- 5.8 U/mmol LDL-cholesterol, p < 0.05) were significantly increased in diabetic patients. The concentration of BCD, 7-OH-GPC and lyso-PC in LDL did not differ between diabetic patients and control subjects. No significant correlations were demonstrated between the measured indicators of LDL oxidation and carotid IMT.


CONCLUSIONS
Levels of BCD, 7-OH-GPC and lyso-PC, that is, intermediary products of LDL oxidation, were not significantly elevated, but ketocholesterol and Ox-apoB, that is, stable end products of the oxidation process, were increased in diabetic patients. We conclude that in vivo oxidation of LDL is increased, even in subjects with well- or moderately controlled type 2 diabetes.
Scheffer
P G
PG
Metabolic Laboratory, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands. p.scheffer@vumc.nl
Henry
R M A
RM
Wever
E J M
EJ
van Rooij
G J
GJ
Bos
G
G
Heine
R J
RJ
Dekker
J M
JM
Diamant
M
M
Stehouwer
C D A
CD
Nijpels
G
G
Blankenstein
M A
MA
Teerlink
T
T
D000368:Aged; D002339:Carotid Arteries / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007653:Ketocholesterols / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000097:blood; D012016:Reference Values; D012044:Regression Analysis; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
D006442:Glycated Hemoglobin; D007653:Ketocholesterols; D008077:Lipoproteins, LDL; D010743:Phospholipids