Plasma levels of tissue inhibitor of metalloproteinase-1 in patients with type 1 diabetes mellitus associate with early diabetic neuropathy and nephropathy.

Nektaria Papadopoulou-Marketou,Andreas C Eriksson,Jeanette Wahlberg,Per A Whiss,Lars Hyllienmark,Ioannis Papassotiriou

doi:10.1177/14791641211002470

Abstract

Background:Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been suggested as a marker for abnormal regulation of tissue remodelling in type 1 diabetes. Metalloproteinase-9 (MMP-9) has been associated with matrix turnover, and Neutrophil gelatinase associated lipocalin (NGAL) is a marker of tubular injury in diabetic nephropathy. The aim was to analyse these biomarkers to unmask early diabetic complications.Methods:Thirty-three type 1 diabetes patients, aged 20–35 years, and disease duration 20 ± 5.3 years were included. Along with clinical examination, neurophysiological measurements, routine biochemistry, plasma concentrations of TIMP-1, MMP-9 and NGAL were determined with immunoenzymatic techniques.Results:TIMP-1 correlated with abnormal unilateral and bilateral vibratory sense foot perception (r = −0.49 and r = −0.51, respectively), foot neuropathy impairment assessment score (NIA; r = −0.55), neuropathy symptom assessment score (r = 0.42), microalbuminuria (r = 0.50) and eGFR (r = −0.45). MMP-9 correlated with impaired foot NIA (r = 0.51). Multiple regression analysis showed an association for TIMP-1 (p = 0.004) with impaired neurophysiological examinations and renal dysfunction along with NGAL (p = 0.016 and p = 0.015 respectively).Conclusions:This study suggests that plasma levels of TIMP-1, MMP-9 and NGAL may serve as useful biomarkers in unravelling subclinical neuropathy and nephropathy in type 1 diabetes.

Highlights

Type 1 diabetes is linked to an increased risk of macro- and microvascular complications but the leading mechanisms have not been fully established.[1,2,3]Peripheral diabetes neuropathy is a common microvascular complication of type 1 diabetes, which increases in frequency with the duration of disease and its progression is associated with a poor metabolic control
Tissue inhibitor of metalloproteinase-1 (TIMP-1) in plasma from patients with type 1 diabetes had a mean value of 91 ng/mL
Past studies have shown an association between proinflammatory cytokines such as IL-1β and TNF-α and virus infected or immune activated mononuclear phagocytes with up-regulated Tissue inhibitor of metalloproteinase (TIMP)-1.15 Several lines of evidence have shown that TIMP-1 may serve as a biomarker of ongoing adverse cardiac remodelling[10] as changes in the plasma levels of TIMP-1 according to several large-scale cardiovascular outcome studies have been associated with increased mortality

Summary

Introduction

Peripheral diabetes neuropathy is a common microvascular complication of type 1 diabetes, which increases in frequency with the duration of disease and its progression is associated with a poor metabolic control. Earlier studies have provided evidence that nephropathy in subjects with type 1 diabetes is associated with. Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been suggested as a marker for abnormal regulation of tissue remodelling in type 1 diabetes. Metalloproteinase-9 (MMP-9) has been associated with matrix turnover, and Neutrophil gelatinase associated lipocalin (NGAL) is a marker of tubular injury in diabetic nephropathy. Multiple regression analysis showed an association for TIMP-1 (p = 0.004) with impaired neurophysiological examinations and renal dysfunction along with NGAL (p = 0.016 and p = 0.015 respectively). Conclusions: This study suggests that plasma levels of TIMP-1, MMP-9 and NGAL may serve as useful biomarkers in unravelling subclinical neuropathy and nephropathy in type 1 diabetes

Methods

Results

Conclusion