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Diabetes Care Publish Ahead of Print published online ahead of print June 11, 2007
DOI: 10.2337/dc07-0162
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Original Research

MMP-2 dysregulation in Type 1 Diabetes Mellitus

Kathryn M. Thrailkill, MD1, Robert C. Bunn, PhD1, Cynthia S. Moreau, RN1, Gael E. Cockrell, BS1, Pippa M. Simpson, PhD1, Hannah N. Coleman, BS1, J. Paul Frindik, MD1, Stephen F. Kemp, MD1 and John L. Fowlkes, MD1

1Department of Pediatrics, University of Arkansas for Medical Sciences, and Arkansas Children's Hospital Research Institute, Little Rock, AR, USA, 72202

thrailkillkathrynm{at}uams.edu

ABSTRACT

OBJECTIVE - : Dysregulation of MMP-2 may contribute pathologically to the development of diabetic complications, including diabetic retinopathy and coronary and peripheral arterial disease. Our objective was to explore whether systemic MMP-2 dysregulation could be demonstrated in T1DM, and to determine how MMP-2 concentration relates to disease status.

RESEARCH DESIGN AND METHODS - : In this cross-sectional study, MMP-2 concentrations and MMP-2 activity were measured in plasma and timed urine samples from 93 T1DM and 50 healthy control subjects, ages 14-40 years. Relationships between MMP-2 concentrations in these biological fluids and patient characteristics (gender, age, duration of T1DM), indices of glycemic control (HbA1c, fasting plasma glucose, CGMS average daily glucose) and measurements of renal function (UAE, GFR) were examined.

RESULTS - : Urine and plasma MMP-2 concentrations and plasma MMP-2 activity were all significantly elevated in T1DM subjects, compared with control subjects. Urine MMP-2 concentrations, in particular, were correlated with several clinical parameters which infer increased risk for diabetic co-morbidity, and specifically for diabetic nephropathy, including higher HbA1c, longer duration of disease, evidence of renal hyperfiltration, and the presence of microalbuminuria.

CONCLUSIONS - : Urine and plasma MMP-2 concentrations are dysregulated in T1DM; urinary excretion of MMP-2, in particular, might provide a unique biomarker of diabetes-induced intrarenal pathology.


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