Impaired endothelium-dependent vasodilation in type 2 diabetes. Relation to LDL size, oxidized LDL, and antioxidants.
OBJECTIVE
To search for determinants of endothelial dysfunction in type 2 diabetes.


METHODS
We performed a comprehensive analysis of cardiovascular risk markers and measured blood flow responses to endothelium-dependent (acetylcholine [ACh] and NG-monomethyl-L-arginine) and -independent (sodium nitroprusside [SNP]) vasoactive agents in 30 nonsmoking men with type 2 diabetes (age 51 +/- 1 years, BMI 27.8 +/- 0.4 kg/m2, HbA1c 7.4 +/- 0.3%) and 12 matched normal control men.


RESULTS
ACh-induced vasodilation was 37% lower in type 2 diabetic (6.1 +/- 0.5) than in normal subjects (9.7 +/- 1.5 ml.dl-1.min-1, P < 0.01), while flows during SNP were similar (9.1 +/- 0.6 vs. 9.9 +/- 1.3 ml.dl-1.min-1, NS). The ratio of endothelium-dependent vs. -independent flow (ACh:SNP ratio) was 31% lower in type 2 diabetic (0.70 +/- 0.05) than in normal subjects (1.10 +/- 0.18, P < 0.01). Total (2.2 +/- 0.4 vs. 1.3 +/- 0.2 mmol/l, P < 0.05), VLDL, and intermediate-density lipoprotein triglycerides were significantly higher, and the mean LDL particle diameter was significantly smaller in type 2 diabetic than in normal subjects. The lag times for LDL oxidation by Cu2+ in vitro were similar in patients with type 2 diabetes (183 +/- 7) and in normal subjects (183 +/- 9 min, NS). Measured and calculated (sum of concentration of individual antioxidants in serum) total peroxyl radical-trapping capacities (TRAPs) were comparable between the groups. In the patients with type 2 diabetes, LDL size was significantly correlated with endothelium-dependent vasodilation (r = 0.43, P < 0.05), serum triglycerides (r = -0.75, P < 0.001), and the lag time for LDL oxidation in vitro (r = 0.38, P < 0.05). HbA1c was inversely correlated with the lag time for LDL oxidation in vitro (r = -0.41, P < 0.05) and TRAP.


CONCLUSIONS
In summary, patients with type 2 diabetes exhibited impaired endothelium-dependent vasodilation in vivo, elevated serum triglycerides, decreased LDL size, and normal antioxidant capacity. Of these parameters, LDL size was significantly correlated with endothelial function.
Mäkimattila
S
S
Department of Medicine, Helsinki University Central Hospital, Finland.
Liu
M L
ML
Vakkilainen
J
J
Schlenzka
A
A
Lahdenperä
S
S
Syvänne
M
M
Mäntysaari
M
M
Summanen
P
P
Bergholm
R
R
Taskinen
M R
MR
Yki-Järvinen
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000975:Antioxidants / Q000032:analysis*; D001053:Apolipoproteins / Q000097:blood; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D002784:Cholesterol / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D012016:Reference Values; D012307:Risk Factors; D014664:Vasodilation / Q000187:drug effects; D014801:Vitamin A / Q000097:blood; D014810:Vitamin E / Q000097:blood; D019207:beta Carotene / Q000097:blood; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000975:Antioxidants; D001053:Apolipoproteins; D008074:Lipoproteins; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D019207:beta Carotene; D014801:Vitamin A; D014810:Vitamin E; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D002784:Cholesterol; D000109:Acetylcholine