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KMID : 0377220000250020066
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Medical Journal of Chosun Univercity
2000 Volume.25 No. 2 p.66 ~ p.74
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Serum concentration of Metalloproteinase-9 in Type 2 Diabetic patients
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Kim Sang-Yong
Kim Hee-Joong
Joo Yoo-Chul
Choi Dong-Hyun
Bae Hak-Yeon
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Abstract
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Purpose : Diabetic nephropathy is a serious complication of diabetes and accounts for much of its morbidity and mortality. It is well known that the overt clinical phase of diabetic nephropathy is preceded for many years by the presence of microalbuminuria. Microalbuminuria is thought to be a marker of widespread vascular damage and may underlie the propensity toward severe extrarenal vascular disease in microalbuminuric patients. Metalloproteinase-9 has a broad substrate specificity for native collagens as well as proteoglycan and elastin. One study reported that an increased plasma metalloproteinase-9 concentration precedes the development of microalbuminuria in type 2 diabetic patients. Another study reported that a high glucose concentration cause a abnormality on the activity of metalloproteinase by the mesangeal cell. The purpose of the present study was to examine whether palsma metalloproteinase-9 concentrations are altered at various complications in type 2 diabetic patients.
Methods : Sixty patients with type 2 diabetes and thirty healthy control were recruited for the present study. No patient had any malignancy or history of heart disease, liver disease, collagen disease. We recorded age, duration of diabetes, and blood pressure. After an overnight fast, blood was drawn from an antecubita1 vein of measurement of glucose, metalloproteinase-9, HbA1C, and serum creatinine. To measure plasma concentration of metalloproteinase-9, a one step sandwich enzyme immunoassay using two monoclonal antibodies was used. Patients were divided into two group according to the presence or abscence of microalbuminuria. The groups were then compared with regard to clinical and laboratory characteristics and serum concentration of metalloproteinase-9.
Results : The mean serum levels of metalloproteinase-9 in diabetic patients (62.32±25.83ng/㎖) were significantly higher than in healthy controls(12.92±4.97ng/㎖) (p<01). The mean serum levels of metalloproteinase-9 in diabetic patients with microalbuminuria(81.16±41.43ng/㎖) were significantly higher than in those with normoalbuminuria(31.48±7.34ng/㎖) (p<01) and much more than in healthy control(12.92±4.97ng/㎖) (p<05). Furthermore, the severity of nephropathy were closely associated with the serum metalloproteinase-9 level and the serum metalloproteinase-9 level was significantly correlated with microalbuminuria. The mean serum level of metalloproteinase-9 in diabetic patients with retinopathy(61.74±39.07ng/㎖) was significantly higher than in those with no retinopathy(34.98±9.02ng/㎖) (p<05). But, in diabetic patients with normoalbuminuria, there is no difference between the groups with retinopathy versus no retinopathy.
Conclusion : In summary, a sustained increase in serum metalloproteinase-9 in patients with type 2 diabetes is associated with a high risk for the development of microalbuminuria. The results of this study suggest that the serum rnetalloproteinase-9 was a useful and noninvasive marker for the development of diabetic nephropathy. It could be also used to predict the development of diabetic complications and to assess therapeutics or the prognosis of diabetes. The usefulness of this model will be clarified by a larger scale and serial study.
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KEYWORD
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metalloproteinase-9, microalbuminuria, type 2 diabetes
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