Impaired endothelium-dependent vasodilation in type 9 diabetes - Relation to LDL size, oxidized LDL, and antioxidants

OBJECTIVE - To search for determinants of endothelial dysfunction in type 2 diabetes. RESEARCH DESIGN AND METHODS - We performed a comprehensive analysis of card iovascular risk markers and measured blood flow responses to endothelium-de pendent (acetylcholine [ACh] and N-G-monomethyl-L-arginine) and -independen t (sodium nitroprusside [SNP]) vasoactive agents in 30 nonsmoking men with type 2 diabetes (age 51 +/- 1 years, BMI 27.8 +/- 0.4 kg/m(2), HbA(1c) 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), whi le 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:SN P ratio) was 31% lower in type 2 diabetic (0.70 +/- 0.05) than in normal su bjects (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 o xidation by Cu2+ in vitro were similar in patients with type 2 diabetes (18 3 +/- 7) and in normal subjects (183 +/- 9 min, NS). Measured and calculate d (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 wi th endothelium-dependent vasodilation (r = 0.43, P < 0.05), serum triglycer ides (r = -0.75, P < 0.001), and the lag time for LDL oxidation in vitro (r = 0.38, P < 0.05). HbA(1c) tvas 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, d ecreased LDL size, and normal antioxidant capacity. Of these parameters, LD L size was significantly correlated with endothelial function.