Matrix metalloproteinase-2 dysregulation in type 1 diabetes.
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.


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.
Thrailkill
Kathryn M
KM
Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock, Arkansas 72202, USA. thrailkillkathrynm@uams.edu
Bunn
Robert C
RC
Moreau
Cynthia S
CS
Cockrell
Gael E
GE
Simpson
Pippa M
PM
Coleman
Hannah N
HN
Frindik
J Paul
JP
Kemp
Stephen F
SF
Fowlkes
John L
JL
D000293:Adolescent; D000328:Adult; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000209:etiology* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000378:metabolism* / Q000652:urine
D020778:Matrix Metalloproteinase 2