| Peer-Reviewed

Matrix Metalloproteinase-2 as Potential Marker of Early Nephropathy in Type 1 Diabetes

Received: 18 January 2015     Accepted: 29 January 2015     Published: 6 February 2015
Views:       Downloads:
Abstract

Background: Early detection of diabetic nephropathy (DN) is important. Matrix metalloproteinases-2 (MMP-2) regulates a variety of cellular functions including apoptosis and angiogenesis. Diabetic environment stimulates the secretion of MMP-2 that is considered to participate in DN. Objectives: We conducted this study to investigate the level of MMP-2 as a potential marker of early nephropathy in type 1 diabetes. Methods: The total number of the study was 300 participants, among them 100 participants, were healthy volunteers control group with comparable age and sex to other participants (Group 1). The remaining 200 participants were suffering from type 1 diabetes and were categorized according to duration of diabetes into 100 patients had disease duration less than 5 years and all of them non microalbuimnuric (Group 2) and the last 100 patients had disease duration more than 5 years (Group 3). All subjects were submitted to complete clinical examination; routine laboratory investigations, including; random blood sugar (RBS); glycosylated hemoglobin (HbA1C) and quantitative determination of microalbuminuria (MA) for DN. Specific laboratory investigation for MMP-2 by enzyme-linked immunosorbent assay. Results: RBS and HbA-1c were significantly higher in group 3 than group 2. MA significantly detected only in group 3. MMP-2 was significantly higher in group 3 than the other groups 1, 2 and in the meantime significantly higher in group 2 than 1. MMP-2 starts to rise early before the onset of MA in group 2. Eventually duration of diabetes, RBS, HbA1c and MA were positively correlated with the MMP-2 level. (r=0. 44; P<0.05), (r=0. 43; P<0.05), (r=0. 58; P<0.05) and (r=0. 71; P<0.001) respectively. MMP-2 cutoff level of ≥ 311 ng/ml had a greater sensitivity and specificity for identifying MA (P<0.001). Conclusion: MMP-2 level pre-date the clinical evidence of MA, may serve as an important predictor for early development of DN and a potential marker of severity.

Published in American Journal of Internal Medicine (Volume 3, Issue 1)
DOI 10.11648/j.ajim.20150301.11
Page(s) 1-5
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2015. Published by Science Publishing Group

Keywords

Matrix Metalloprteinase-2, Type1 Diabetes Mellitus, Microalbuminuria, Diabetic Nephropathy

References
[1] DCCT: Implications of the Diabetes Control and Complications Trial. American Diabetes Association. Diabetes.1993; 42:1555–1558,
[2] Monnier VM, Bautista O, Kenny D, Sell DR, Fogarty J, Dahms W, Cleary PA,Lachin J, Genuth S: Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. DCCT Skin Collagen Ancillary Study Group. Diabetes Control and Complications Trial.Diabetes.1999; 48:870–880
[3] Mauch C: Regulation of connective tissue turnover of cell-matrix interactions. Arch Dermatol Res.1998; 290: S30–S36
[4] Nagase H, Woessner JF Jr: Matrix metalloproteinases. J Biol Chem.1999; 274:21491–21494.
[5] Maisonneuve P, Agodoa L, Gellert Ret al. Distribution of primary renal diseases leading to end-stage renal failure in the United States,Europe, and Australia/New Zealand: results from an international comparative study. Am J Kidney Dis.2000; 35: 157–165
[6] Gilbert RE, Cooper ME. The tubulointerstitium in progressive diabetic kidney disease: more than an aftermath of glomerular injury? Kidney Int.1999; 56: 1627–1637
[7] Furness PN: (1997) Basement membrane synthesis and degradation. J Pathol, 183 (1): 1-3.
[8] Lenz O, Elliot SJ, Stetler-Stevenson WG. Matrix metalloproteinases in renal development and disease. J Am Soc Nephrol.2000; 11: 574–581
[9] McLennan SV, Kelly DJ, Cox AJet al. Decreased matrix degradation in diabetic nephropathy: effects of ACE inhibition on the expression and activities of matrix metalloproteinases.Diabetologia. 2002; 45: 268–27
[10] Hernandez-Barrantes S, Shimura Y, Soloway PD, Sang QA, Fridman R: Differential roles of TIMP-4 & TIMP-2inpro-MMP-2 activation by MT1-MMP.Biochem Biophys Res Commun.2001; 281:126–130
[11] Akahane T, Akahane M, Shah A, Thorgeirsson UP. TIMP-1stimulates proliferation of human aortic smooth muscle cells and Ras effector pathways. Biochem Biophys Res Commun.2004; 1: 440-5.
[12] Han X, Sun Y, Scott S, Bleich D. Tissue inhibitor of metalloproteinase-1 prevents cytokine -mediated dysfunction and cytotoxicity in pancreatic islets and beta-cells. Diabetes.2001; 50: 1047-55
[13] American Diabetes Association: Diabetic nephropathy (Position Statement). Diabetes Care.2000; 23 (Suppl. 1): S69–S72
[14] Bahman P, Tabaei M , AL-K assab , Liza L,I lag ,Cathernen M, Zawacki RN and William H. Herman. Does Microalbuminuria Predict Diabetic Nephropathy?. Diabetes Care.2001; 24:1560 –1566
[15] Zelmanovitz T, Gerchmann F, Balthazar A, Thomazelli F, Matos J, and Canani L, : Diabetic nephropathy: Diabetology and metabolic syndrome. 2009; 1:10.
[16] Sedegheh Gharagozlian, Katja Svennevig, Hans-Jacob Bangstad , JanOlof Winberg and Svein Olav Kolset..MMP in subjects with type 1diabetes BMC; Clinical Pathology.2009; 9:7 doi: 10. 1186 /1472 -6890-9-7
[17] Mai M Y, Hoda A, Sawsan T, Hanaa S, Ola M, Manal A M, Nagham M, B, A., MMP-2 as a marker of microvascular complications in Children and Adolescents with Type 1 Diabetes Mellitus. Macedonian Journal of Medical Sciences.2011; 15; 4 (1): 81-88. doi:10.3889/MJMS.1857-5773.2011.0151.
[18] Thrailkill KM, Bunn RC, Moreau CS, Cockrell GE, Simpson PM, Coleman HN, Frindik JP, Kemp SF, Fowlkes JL: MMP-2 Dysregulation in Type I Diabetes. Diabetes Care.2007; 30 (9): 2321-2326
[19] Flory B, Glowinska B, urban M, Peczynska J. MMP-2 and MMP-9 and their inhibitors TIMP-1 and TIMP-2 levels in children and adolescents with type 1 diabetes, Edokrynol Diabetol Chor Przemiany Materii Wieku Rozw.2006; 12 (3): 184-189.
[20] Ming-Yuh Shiau, Shih-Tzer Tsai, Kan-Jen Tsai, Ming-Lih Haung, Increased circulatory MMP-2 and MMP-9 levels and activities in patients with type 1 diabetes mellitus. THE MOUNT SINAI JOURNAL OF MEDICINE.2006; Vol. 73 No. 7.
[21] Symeonidis C(1), Papakonstantinou E, Galli A, Tsinopoulos I, Mataftsi A, Batzios S, Dimitrakos SA.. Matrix metalloproteinase (MMP-2, -9) and tissue inhibitor (TIMP-1, -2) activity in tear samples of pediatric type 1 diabetic patients: MMPs in tear samples from type 1 diabetes. Graefes Arch Clin Exp Ophthalmol.2013; 251 (3): 741-9.
[22] Kanwar K, Wada J, Lin Sun, Ping Xie, Elisabith I, Sumnat C, and Nad Farhad R: Diabetic nephropathy: Mechanisms of renal disease progression: Exp Biol Med.2007; 233:4-11.
[23] Bangstad HJ, Osterby R, Dahl-Jorgensen K, Berg KJ, Hartmann A, Hanssen KF: Improvement of blood glucose control in IDDM patients retards the progression of morphological changes in early diabetic nephropathy. Diabetologia.2007; 37 (5): 483-490.
[24] Zelmanovitz T, Gerchmann F, Balthazar A, Thomazelli F, Matos J, and Canani L, : Diabetic nephropathy: Diabetology and metabolic syndrome. 2009; 1:10.
[25] Sophia Zoungas, Sophia Zoungas, Mark Woodward, Qiang Li, Mark E. Cooper, Pavel Hamet et al. (2014). Impact of age, age at diagnosis and duration of diabetes on the risk of macrovascular and microvascular complications and death in type 2 diabetes. Diabetologia.2014;DOI: 10. 1007 /s00125-014 -3369 -7
[26] Jacek Rysz, Maciej Banach, Robert A. Stolarek, Jaroslaw Pasnik, et al (2007). MMP-2 and MMP-9 and metalloproteinase tissue inhibitors TIMP-1 and TIMP-2 in DN.JNEPHROL.2007;; 20: 444-452
[27] Messent JWC, Elliott TG&Hill RD, et al. (1992) Prognostic significance of microalbuminuria in Insulin- dependent diabetes mellitus: A twenty-three year follow-up study. Kidney Int; 41: 836−839
[28] Derosa G, Avanzini MA, Geroldi D, Fogari R, Lorini R, De Silvestri A,et al: (2005) Matrix MMP- 2may be a marker of microangiopathy in children and adolescents with type I diabetes Diabetes Res Clin Pract.; 70 (2): 119-125
Cite This Article
  • APA Style

    Mohamed Fouad, Maher Boraie. (2015). Matrix Metalloproteinase-2 as Potential Marker of Early Nephropathy in Type 1 Diabetes. American Journal of Internal Medicine, 3(1), 1-5. https://doi.org/10.11648/j.ajim.20150301.11

    Copy | Download

    ACS Style

    Mohamed Fouad; Maher Boraie. Matrix Metalloproteinase-2 as Potential Marker of Early Nephropathy in Type 1 Diabetes. Am. J. Intern. Med. 2015, 3(1), 1-5. doi: 10.11648/j.ajim.20150301.11

    Copy | Download

    AMA Style

    Mohamed Fouad, Maher Boraie. Matrix Metalloproteinase-2 as Potential Marker of Early Nephropathy in Type 1 Diabetes. Am J Intern Med. 2015;3(1):1-5. doi: 10.11648/j.ajim.20150301.11

    Copy | Download

  • @article{10.11648/j.ajim.20150301.11,
      author = {Mohamed Fouad and Maher Boraie},
      title = {Matrix Metalloproteinase-2 as Potential Marker of Early Nephropathy in Type 1 Diabetes},
      journal = {American Journal of Internal Medicine},
      volume = {3},
      number = {1},
      pages = {1-5},
      doi = {10.11648/j.ajim.20150301.11},
      url = {https://doi.org/10.11648/j.ajim.20150301.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajim.20150301.11},
      abstract = {Background: Early detection of diabetic nephropathy (DN) is important. Matrix metalloproteinases-2 (MMP-2) regulates a variety of cellular functions including apoptosis and angiogenesis. Diabetic environment stimulates the secretion of MMP-2 that is considered to participate in DN. Objectives: We conducted this study to investigate the level of MMP-2 as a potential marker of early nephropathy in type 1 diabetes. Methods: The total number of the study was 300 participants, among them 100 participants, were healthy volunteers control group with comparable age and sex to other participants (Group 1). The remaining 200 participants were suffering from type 1 diabetes and were categorized according to duration of diabetes into 100 patients had disease duration less than 5 years and all of them non microalbuimnuric (Group 2) and the last 100 patients had disease duration more than 5 years (Group 3). All subjects were submitted to complete clinical examination; routine laboratory investigations, including; random blood sugar (RBS); glycosylated hemoglobin (HbA1C) and quantitative determination of microalbuminuria (MA) for DN. Specific laboratory investigation for MMP-2 by enzyme-linked immunosorbent assay. Results: RBS and HbA-1c were significantly higher in group 3 than group 2. MA significantly detected only in group 3. MMP-2 was significantly higher in group 3 than the other groups 1, 2 and in the meantime significantly higher in group 2 than 1. MMP-2 starts to rise early before the onset of MA in group 2. Eventually duration of diabetes, RBS, HbA1c and MA were positively correlated with the MMP-2 level. (r=0. 44; P<0.05), (r=0. 43; P<0.05), (r=0. 58; P<0.05) and (r=0. 71; P<0.001) respectively. MMP-2 cutoff level of ≥ 311 ng/ml had a greater sensitivity and specificity for identifying MA (P<0.001). Conclusion: MMP-2 level pre-date the clinical evidence of MA, may serve as an important predictor for early development of DN and a potential marker of severity.},
     year = {2015}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Matrix Metalloproteinase-2 as Potential Marker of Early Nephropathy in Type 1 Diabetes
    AU  - Mohamed Fouad
    AU  - Maher Boraie
    Y1  - 2015/02/06
    PY  - 2015
    N1  - https://doi.org/10.11648/j.ajim.20150301.11
    DO  - 10.11648/j.ajim.20150301.11
    T2  - American Journal of Internal Medicine
    JF  - American Journal of Internal Medicine
    JO  - American Journal of Internal Medicine
    SP  - 1
    EP  - 5
    PB  - Science Publishing Group
    SN  - 2330-4324
    UR  - https://doi.org/10.11648/j.ajim.20150301.11
    AB  - Background: Early detection of diabetic nephropathy (DN) is important. Matrix metalloproteinases-2 (MMP-2) regulates a variety of cellular functions including apoptosis and angiogenesis. Diabetic environment stimulates the secretion of MMP-2 that is considered to participate in DN. Objectives: We conducted this study to investigate the level of MMP-2 as a potential marker of early nephropathy in type 1 diabetes. Methods: The total number of the study was 300 participants, among them 100 participants, were healthy volunteers control group with comparable age and sex to other participants (Group 1). The remaining 200 participants were suffering from type 1 diabetes and were categorized according to duration of diabetes into 100 patients had disease duration less than 5 years and all of them non microalbuimnuric (Group 2) and the last 100 patients had disease duration more than 5 years (Group 3). All subjects were submitted to complete clinical examination; routine laboratory investigations, including; random blood sugar (RBS); glycosylated hemoglobin (HbA1C) and quantitative determination of microalbuminuria (MA) for DN. Specific laboratory investigation for MMP-2 by enzyme-linked immunosorbent assay. Results: RBS and HbA-1c were significantly higher in group 3 than group 2. MA significantly detected only in group 3. MMP-2 was significantly higher in group 3 than the other groups 1, 2 and in the meantime significantly higher in group 2 than 1. MMP-2 starts to rise early before the onset of MA in group 2. Eventually duration of diabetes, RBS, HbA1c and MA were positively correlated with the MMP-2 level. (r=0. 44; P<0.05), (r=0. 43; P<0.05), (r=0. 58; P<0.05) and (r=0. 71; P<0.001) respectively. MMP-2 cutoff level of ≥ 311 ng/ml had a greater sensitivity and specificity for identifying MA (P<0.001). Conclusion: MMP-2 level pre-date the clinical evidence of MA, may serve as an important predictor for early development of DN and a potential marker of severity.
    VL  - 3
    IS  - 1
    ER  - 

    Copy | Download

Author Information
  • Nephrology unit, Internal Medicine Departments, Zagazig University Hospital, Zagazig, Egypt

  • Clinical Pathology Departments, Zagazig University Hospital, Zagazig, Egypt

  • Sections