Inverse correlation between activated protein C generation and carotid atherosclerosis in Type 2 diabetic patients.
OBJECTIVE
Activated protein C (APC) is a key regulator of the clotting system and immune responses. We studied the relationship between the degree of atherosclerosis as measured by the intima-media thickness (IMT) of carotid artery and APC generation in Type 2 diabetic patients.


METHODS
Eighty-seven Type 2 diabetic patients and 35 control subjects participated. APC generation was assessed by the plasma APC-protein C inhibitor complex (APC-PCI) levels and the mean IMT of carotid artery was measured by ultrasonography. The plasma levels of the thrombin-anti-thromobin complex (TAT) and platelet-derived growth factor (PDGF) were measured by enzyme-linked immunoassays.


RESULTS
Plasma TAT levels were significantly higher in diabetic patients [2.03 (1.12, 2.56) ng/ml, median (25th, 75th percentile)] compared with control subjects [0.85 (0.55, 2.08) ng/ml, P < 0.01]. Plasma APC-PCI levels were significantly lower in diabetic patients [0.93 (0.74, 1.22) ng/ml], than in control subjects [1.66 (1.25, 2.36) ng/ml, P < 0.001]. The mean IMT was significantly increased in diabetic patients (0.881 +/- 0.242 mm; mean +/- sd) compared with control subjects (0.669 +/- 0.140 mm; P < 0.01). Univariate analysis showed a significant and inverse correlation between plasma APC-PCI levels and mean IMT (r = -0.32, P < 0.005), and multivariate regression analysis confirmed the independent correlation (P < 0.05). Moreover, plasma APC-PCI levels significantly and inversely correlated with plasma PDGF levels in diabetic patients (r = -0.30, P < 0.01).


CONCLUSIONS
These results suggest that decreased APC generation is associated with vascular atherosclerotic changes in Type 2 diabetic patients.
Matsumoto
K
K
Department of Diabetes and Endocrinology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Yano
Y
Y
Gabazza
E C
EC
Araki
R
R
Bruno
N E
NE
Suematsu
M
M
Akatsuka
H
H
Katsuki
A
A
Taguchi
O
O
Adachi
Y
Y
Sumida
Y
Y
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology; D017536:Carotid Artery, Common / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003925:Diabetic Angiopathies / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000378:metabolism*; D018046:Protein C Inhibitor / Q000097:blood*; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
D015415:Biomarkers; D011486:Protein C; D018046:Protein C Inhibitor