Elevated circulating levels of matrix metalloproteinase-9 in type 1 diabetic patients with and without retinopathy.
OBJECTIVE
Tissue expression pattern of matrix metalloproteinases (MMPs) and their inhibitors TIMPs indicate that microvascular complications of diabetes mellitus are associated with extracellular matrix remodelling. We investigated whether circulating levels of MMP-9 and TIMP-1 are altered in diabetic retinopathy and whether they might serve as biological markers of ocular complications in type 1 diabetes.


METHODS
We recruited 47 type 1 diabetic patients free of vascular complications (n=40) or with retinopathy (n=14). Patients with macroangiopathy, neuropathy and nephropathy were excluded. A group of nondiabetic control subjects (n=35) was also constituted for comparative purposes. Peripheral blood levels of MMP-9 and TIMP-1 were determined using immunoenzymatic assays.


RESULTS
Type 1 diabetic subjects exhibited significantly higher circulating levels of both MMP-9 and MMP-9/TIMP-1 ratio, as well as a tendency to increased serum TIMP-1 levels relative to nondiabetic controls (p<0.001). Diabetic patients with retinopathy also displayed elevated systemic values of MMP-9 and MMP-9/TIMP-1 ratio when compared to patients without retinopathy (p<0.05). Logistic regression analysis identified diabetes duration firstly (P<0.01), and MMP-9 serum levels secondly (P<0.01) as significant and independent variables associated with the existence of retinopathy.


CONCLUSIONS
Our data suggest that peripheral blood MMP-9 levels might serve as surrogate biomarkers of retinopathy in type 1 diabetic patients free of other vascular complications.
Jacqueminet
S
S
Service de Diabétologie, Groupe Hospitalier Pitié-Salpêtrière, 47-83 boulevard de l'hôpital, F75651 Paris Cedex 13, France. sophie.jacqueminet@psl.aphp.fr
Ben Abdesselam
O
O
Chapman
M-J
MJ
Nicolay
N
N
Foglietti
M-J
MJ
Grimaldi
A
A
Beaudeux
J-L
JL
D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications* / Q000473:pathology; D003930:Diabetic Retinopathy / Q000097:blood* / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
D019715:Tissue Inhibitor of Metalloproteinase-1; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9