Advanced endothelial dysfunction in diabetic patients with multiple risk factors; importance of insulin resistance.
OBJECTIVE
Endothelial dysfunction is considered an early event in the development of atherosclerosis. The present study was undertaken to determine whether the accumulation of cardiovascular risk factors and insulin resistance are associated with endothelial function in diabetic patients.


METHODS
101 patients with type 2 diabetes without macroangiopathy stratified by the number of cardiovascular risk factors (dyslipidemia, hypertension, obesity) and 9 normal control subjects were studied for vascular endothelial functions by measuring flow-mediated vasodilation (FMD) using a high-resolution ultrasound method, brachial-ankle pulse wave velocity (baPWV), carotid intima-media thickness (IMT), and the ankle-brachial index (ABI).


RESULTS
FMD negatively correlated with baPWV and carotid IMT, and positively correlated with ABI. FMD was significantly lower in diabetic patients associated with 3 other risk factors than in those with diabetes alone. In subjects with fasting plasma glucose < or = 140mg/dL, FMD showed significant negative correlations with fasting insulin levels and homeostasis model assessment (HOMA)-R. Multivariate analysis revealed that insulin resistance as represented by HOMA-R and systolic blood pressure showed a significant association with impaired FMD.


CONCLUSIONS
The present results suggest that the accumulation of cardiovascular risk factors is associated with endothelial dysfunction in diabetic patients, and that insulin resistance as well as high blood pressure could play a pathogenic role in the development of endothelial dysfunction.
Tsuchiya
Kyoichiro
K
Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan. ktsuchiya.cme@tmd.ac.jp
Nakayama
Chisato
C
Iwashima
Fumiko
F
Sakai
Haruna
H
Izumiyama
Hajime
H
Doi
Masaru
M
Hirata
Yukio
Y
D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006706:Homeostasis; D006801:Humans; D006973:Hypertension; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014664:Vasodilation