Evaluation of metalloproteinase 2 and 9 levels and their inhibitors in diabetic and healthy subjects.
OBJECTIVE
We hypothesized that molecules active in vascular remodeling (i.e. MMPs and their TIMPs) could be modified in diabetic patients, as indirect markers of the diabetes related generalized abnormality of vascular activity. To test this hypothesis, we measured the plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 in type 2 diabetic patients and in healthy subjects.


METHODS
We enrolled 181 diabetic patients and 165 controls. We measured body mass index (BMI), glycosylated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment index (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), lipoprotein(a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), homocysteine (Hct) fibrinogen (Fg), high sensitivity C-reactive protein (hs-CRP), and plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2.


RESULTS
A significant increase (P<0.0001) of BMI, HbA(1c), FPG, FPI, HOMA index, SBP, DBP, TC, LDL-C, Tg, Lp(a), PAI-1, Hct, Fg, and hs-CRP was present in the diabetic group, with a significant decrease (P<0.0001) of HDL-C levels compared to healthy subjects. MMP-2 and MMP-9 levels were significantly higher (P<0.0001) in diabetic patients. Significant TIMP-1, and TIMP-2 increase was also observed (P<0.0001) in the diabetic group.


CONCLUSIONS
Plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 are increased in diabetic patients which may reflect abnormal extracellular matrix (ECM) metabolism.
Derosa
G
G
Department of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS Policlinico S. Matteo, Pavia, Piazzale C. Golgi 2, 27100 Pavia, Italy. giuseppe.derosa@unipv.it
D'Angelo
A
A
Tinelli
C
C
Devangelio
E
E
Consoli
A
A
Miccoli
R
R
Penno
G
G
Del Prato
S
S
Paniga
S
S
Cicero
A F G
AF
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology*; D005109:Extracellular Matrix / Q000201:enzymology; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D012016:Reference Values; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood; D044465:White People
D001786:Blood Glucose; D007328:Insulin; D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9