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. Diabetes Care 30:2321-2326, 2007M atrix metalloproteinases (MMPs) constitute a group of enzymes that hydrolyze protein components of the extracellular matrix (1). The subgroup of MMPs known as gelatinases, specifically gelatinase A (MMP-2) and gelatinase B (MMP-9) digest collagen, denatured collagens (i.e., gelatins), laminin, elastin, and fibronectin, among other substrates (2), and have been implicated in the pathological processes that contribute to fibrotic diseases, tumor progression, and inflammation (1,3,4).Dysregulation of gelatinase activity has also been implicated in the pathophysiology of diabetes complications. Specifically, gelatinase concentrations are increased in the systemic circulation ) and in the vitreous (MMP-2 [6] and MMP-9 [7]) of type 1 diabetic patients with diabetic retinopathy. Elevated retinal levels of MMP-2 and MMP-9 have also been demonstrated in an animal model of diabetic retinopathy (8). Increased circulating concentrations of MMP-2 have been observed in pediatric patients with type 1 diabetes who developed microangiopathy over a 5-year interval (9). Systemic concentrations of MMP-2 and MMP-9, in addition to gelatinase activity levels, are also increased in patients with type 2 diabetes and peripheral arterial disease (10).Data suggesting a link between MMP-2 dysregulation and diabetic nephropathy also exist but appear contra...

Initiation of insulin pump therapy at diagnosis improved glycemic control, was well tolerated, and contributed to improved patient satisfaction with treatment. This study also suggests that earlier use of pump therapy might help to preserve residual β-cell function, although a larger clinical trial would be required to confirm this.

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