Diabetes Care
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Published online June 11, 2007
Diabetes Care 30:2321-2326, 2007
DOI: 10.2337/dc07-0162
© 2007 by the American Diabetes Association
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Pathophysiology/Complications
Original Article

Matrix Metalloproteinase-2 Dysregulation in Type 1 Diabetes

Kathryn M. Thrailkill, MD, Robert C. Bunn, PHD, Cynthia S. Moreau, RN, Gael E. Cockrell, BS, Pippa M. Simpson, PHD, Hannah N. Coleman, BS, J. Paul Frindik, MD, Stephen F. Kemp, MD and John L. Fowlkes, MD

From the Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock, Arkansas

Address correspondence and reprint requests to Kathryn M. Thrailkill, MD, Arkansas Children's Hospital, 800 Marshall St., Little Rock, AR 72202. E-mail: thrailkillkathrynm{at}uams.edu

OBJECTIVE—Dysregulation of matrix metalloproteinase (MMP)-2 may contribute pathologically to the development of diabetes complications, including diabetic retinopathy and coronary and peripheral arterial disease. Our objective was to explore whether systemic MMP-2 dysregulation could be demonstrated in type 1 diabetes 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 type 1 diabetic and 50 healthy control subjects, aged 14–40 years. Relationships between MMP-2 concentrations in these biological fluids and subject characteristics (sex, age, and duration of type 1 diabetes), indexes of glycemic control (A1C, fasting plasma glucose, and continuous glucose monitoring system average daily glucose), and measurements of renal function (urinary albumin excretion and glomerular filtration rate) were examined.

RESULTS—Urine and plasma MMP-2 concentrations and plasma MMP-2 activity were all significantly elevated in type 1 diabetic subjects compared with those in control subjects. Urine MMP-2 concentrations, in particular, were correlated with several clinical parameters that infer increased risk for diabetic comorbidity and specifically for diabetic nephropathy, including higher A1C, longer duration of disease, evidence of renal hyperfiltration, and the presence of microalbuminuria.

CONCLUSIONS—Urine and plasma MMP-2 concentrations are dysregulated in type 1 diabetes; urinary excretion of MMP-2, in particular, might provide a unique biomarker of diabetes-induced intrarenal pathologic processes.

Abbreviations: CGMS, continuous glucose monitoring system • CrCl, creatinine clearance • FPG, fasting plasma glucose • GFR, glomerular filtration rate • MMP, matrix metalloproteinase • TIMP, tissue inhibitor of metalloproteinase • UAE, urinary albumin excretion • UAMS, University of Arkansas for Medical Sciences


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