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

• Published in: Diabetes & vascular disease research Vol. 18; no. 2; p. 14791641211002470
• Main Authors: Papadopoulou-Marketou, Nektaria, Whiss, Per A, Eriksson, Andreas C, Hyllienmark, Lars, Papassotiriou, Ioannis, Wahlberg, Jeanette
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-03-2021
• Subjects: biomarkers; diabetic nephropathy; diabetic neuropathy; Medicin och hälsovetenskap; microvascular complications; Original; TIMP-1; Type 1 diabetes; TIMP-1; Type 1 diabetes; diabetic neuropathy; biomarkers; diabetic nephropathy; microvascular complications
• ISSN: 1479-1641; 1752-8984; 1752-8984
• DOI: 10.1177/14791641211002470

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.