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Published in: Acta Diabetologica 2/2009

01-06-2009 | Original Article

Effects of pentoxifylline and pentosan polysulphate combination therapy on diabetic neuropathy in type 2 diabetes mellitus

Authors: Boglárka Laczy, Judit Cseh, Márton Mohás, Lajos Markó, Mónika Tamaskó, Tamás Kőszegi, Gergő A. Molnár, Zoltán Wagner, László Wagner, István Wittmann

Published in: Acta Diabetologica | Issue 2/2009

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Abstract

Vascular dysfunction, including impaired perfusion has a pivotal role in the pathogenesis of microvascular complications in diabetes mellitus. Both pentoxifylline (PF) and pentosan polysulphate (PPS) are known to improve microcirculation. Antioxidant and antiproteinuric effects of PF are also known. In a placebo-controlled study, we determined the possible efficacy of PF-PPS combination therapy on diabetic neuropathy and nephropathy in type 2 diabetic patients. Patients in Verum group (n = 77) received PF-PPS infusions (100–100 mg/day) for 5 days. Control diabetics (Placebo group; n = 12) were given only saline infusions. Specialized cardiovascular autonomic reflex tests, vibration threshold values and urinary albumin excretion were assessed before and after therapy. In Verum group, autonomic score, indicating the severity of cardiac autonomic dysfunction, decreased after therapy (p ≤ 0.001). Of the reflexes, deep breath and handgrip tests also improved after therapy (p ≤ 0.001). Vibration threshold values, an indicator of the loss of sensory nerve function, were increased after therapy (p ≤ 0.001). Results of cardiac autonomic tests and vibration threshold values remained unaltered in Placebo group. Majority of patients had normalbuminuria, which was not affected by PF-PPS. In conclusion, short-term PF-PPS therapy was effective on cardiovascular autonomic function and vibration perception, whereas it failed to reduce albuminuria within normal range in type 2 diabetic patients.
Literature
1.
go back to reference Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625PubMedCrossRef Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625PubMedCrossRef
2.
go back to reference Evans JL, Goldfine I, Maddux BA, Grodsky GM (2002) Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 5:599–622CrossRef Evans JL, Goldfine I, Maddux BA, Grodsky GM (2002) Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 5:599–622CrossRef
3.
go back to reference Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, Malik RA, Maser RE, Sosenko JM, Ziegler D (2005) Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care 28:956–962PubMedCrossRef Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, Malik RA, Maser RE, Sosenko JM, Ziegler D (2005) Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care 28:956–962PubMedCrossRef
4.
go back to reference Vinik AI, Maser RE, Mitchell BD, Freeman R (2003) Diabetic autonomic neuropathy. Diabetes Care 26:1553–1579PubMedCrossRef Vinik AI, Maser RE, Mitchell BD, Freeman R (2003) Diabetic autonomic neuropathy. Diabetes Care 26:1553–1579PubMedCrossRef
5.
6.
go back to reference de Zeeuw D (2007) Albuminuria: a target for treatment of type 2 diabetic nephropathy. Semin Nephrol 27:172–181PubMedCrossRef de Zeeuw D (2007) Albuminuria: a target for treatment of type 2 diabetic nephropathy. Semin Nephrol 27:172–181PubMedCrossRef
7.
go back to reference McMillan DE (1983) The effect of diabetes on blood flow properties. Diabetes 32:56–63PubMed McMillan DE (1983) The effect of diabetes on blood flow properties. Diabetes 32:56–63PubMed
8.
go back to reference Negrean V, Suciu I, Sampelean D, Cozma A (2004) Rheological changes in diabetic microangiopathy. J Rom Intern Med 42:407–413 Negrean V, Suciu I, Sampelean D, Cozma A (2004) Rheological changes in diabetic microangiopathy. J Rom Intern Med 42:407–413
9.
go back to reference Cameron NE, Eaton SE, Cotter MA, Tesfaye S (2001) Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia 44:1973–1988PubMedCrossRef Cameron NE, Eaton SE, Cotter MA, Tesfaye S (2001) Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia 44:1973–1988PubMedCrossRef
10.
go back to reference Young MJ, Bennett JL, Liderth SA, Veves A, Boulton AJ, Douglas JT (1996) Rheological and microvascular parameters in diabetic peripheral neuropathy. Clin Sci Lond 90:183–187PubMed Young MJ, Bennett JL, Liderth SA, Veves A, Boulton AJ, Douglas JT (1996) Rheological and microvascular parameters in diabetic peripheral neuropathy. Clin Sci Lond 90:183–187PubMed
11.
go back to reference Solerte SB, Fioravanti M (1987) Hemodynamic alterations in long-term insulin-dependent diabetic patients with overt nephropathy: role of blood hyperviscosity and plasma protein changes. Clin Nephrol 28:138–143PubMed Solerte SB, Fioravanti M (1987) Hemodynamic alterations in long-term insulin-dependent diabetic patients with overt nephropathy: role of blood hyperviscosity and plasma protein changes. Clin Nephrol 28:138–143PubMed
12.
go back to reference Solerte SB, Fioravanti M, Cerutti N, Severgnini S, Locatelli M, Pezza N, Rondanelli M, Trecate L, Balza G, Ferrari E (1997) Retrospective analysis of long-term hemorheologic effects of pentoxifylline in diabetic patients with angiopathic complications. Acta Diabetol 34:67–74PubMedCrossRef Solerte SB, Fioravanti M, Cerutti N, Severgnini S, Locatelli M, Pezza N, Rondanelli M, Trecate L, Balza G, Ferrari E (1997) Retrospective analysis of long-term hemorheologic effects of pentoxifylline in diabetic patients with angiopathic complications. Acta Diabetol 34:67–74PubMedCrossRef
13.
go back to reference Böhm L, Roos WP, Serafin AM (2003) Inhibition of DNA repair by pentoxifylline and related methylxantine derivatives. Toxicology 193:153–160PubMedCrossRef Böhm L, Roos WP, Serafin AM (2003) Inhibition of DNA repair by pentoxifylline and related methylxantine derivatives. Toxicology 193:153–160PubMedCrossRef
14.
go back to reference Radfar M, Hadjibabaie M, Rajabipour B, Mojtahedi A, Abdollahi M (2005) Effects of pentoxifylline on oxidative stress and levels of EGF and NO in blood of diabetic type 2 patients; a randomized, double-blind placebo-controlled trial. Biomed Pharmacother 59:302–306PubMedCrossRef Radfar M, Hadjibabaie M, Rajabipour B, Mojtahedi A, Abdollahi M (2005) Effects of pentoxifylline on oxidative stress and levels of EGF and NO in blood of diabetic type 2 patients; a randomized, double-blind placebo-controlled trial. Biomed Pharmacother 59:302–306PubMedCrossRef
15.
go back to reference Lin SL, Chiang WC, Chen YM, Lai CF, Tsai TJ, Hsieh BS (2005) The renoprotective potential of pentoxifylline in chronic kidney disease. J Chin Med Assoc 68:99–105PubMed Lin SL, Chiang WC, Chen YM, Lai CF, Tsai TJ, Hsieh BS (2005) The renoprotective potential of pentoxifylline in chronic kidney disease. J Chin Med Assoc 68:99–105PubMed
16.
go back to reference Chen YM, Lin SL, Chiang WC, Wu KD, Tsai TJ (2006) Pentoxifylline ameliorates proteinuria through suppression of renal monocyte chemoattractant protein-1 in patients with proteinuric primary glomerular diseases. Kidney Int 69:1410–1415PubMed Chen YM, Lin SL, Chiang WC, Wu KD, Tsai TJ (2006) Pentoxifylline ameliorates proteinuria through suppression of renal monocyte chemoattractant protein-1 in patients with proteinuric primary glomerular diseases. Kidney Int 69:1410–1415PubMed
17.
go back to reference Navarro JF, Mora C, Rivero A, Gallego E, Chahin J, Marcia M, Mendez ML, Garcia J (1999) Urinary protein excretion and serum tumor necrosis factor in diabetic patients with advanced renal failure: effects of pentoxifylline administration. Am J Kidney Dis 3:458–463CrossRef Navarro JF, Mora C, Rivero A, Gallego E, Chahin J, Marcia M, Mendez ML, Garcia J (1999) Urinary protein excretion and serum tumor necrosis factor in diabetic patients with advanced renal failure: effects of pentoxifylline administration. Am J Kidney Dis 3:458–463CrossRef
18.
go back to reference Harmankaya O, Seber S, Yilmaz M (2003) Combination of pentoxifylline with angiotensin converting enzyme inhibitors produces an additional reduction in microalbuminuria in hypertensive type 2 diabetic patients. Ren Fail 25:465–470PubMedCrossRef Harmankaya O, Seber S, Yilmaz M (2003) Combination of pentoxifylline with angiotensin converting enzyme inhibitors produces an additional reduction in microalbuminuria in hypertensive type 2 diabetic patients. Ren Fail 25:465–470PubMedCrossRef
19.
go back to reference Navarro JF, Mora C, Muros M, Garcia J (2005) Additive antiproteinuric effect of pentoxifylline in patients with type 2 diabetes under angiotensin II receptor blockade: a short term, randomized, controlled trial. J Am Soc Nephrol 16:2119–2126PubMedCrossRef Navarro JF, Mora C, Muros M, Garcia J (2005) Additive antiproteinuric effect of pentoxifylline in patients with type 2 diabetes under angiotensin II receptor blockade: a short term, randomized, controlled trial. J Am Soc Nephrol 16:2119–2126PubMedCrossRef
20.
go back to reference Aminorroaya A, Janghorbani M, Rezvanian H, Aminian T, Gharavi M, Amini M (2005) Comparison of the effect of pentoxifylline on proteinuria in patients with type 2 diabetes mellitus. Nephron Clin Pract 99:73–77CrossRef Aminorroaya A, Janghorbani M, Rezvanian H, Aminian T, Gharavi M, Amini M (2005) Comparison of the effect of pentoxifylline on proteinuria in patients with type 2 diabetes mellitus. Nephron Clin Pract 99:73–77CrossRef
21.
go back to reference Doctor VM, Sauls V (1982) Isolation and anticoagulant properties of a new sulfated xylan: comparison with heparin and a sodium pentosan polysulfate (SP54). Thromb Res 6:573–578 Doctor VM, Sauls V (1982) Isolation and anticoagulant properties of a new sulfated xylan: comparison with heparin and a sodium pentosan polysulfate (SP54). Thromb Res 6:573–578
22.
go back to reference Freyburger G, Larrue F, Manciet G, Lorient-Roudaut MF, Larrue J, Boisseau MR (1987) Hemorheological changes in elderly subjects-effects of pentosan polysulfate and possible role of leucocyte arachidonic acid metabolism. Thromb Haemost 3:322–325 Freyburger G, Larrue F, Manciet G, Lorient-Roudaut MF, Larrue J, Boisseau MR (1987) Hemorheological changes in elderly subjects-effects of pentosan polysulfate and possible role of leucocyte arachidonic acid metabolism. Thromb Haemost 3:322–325
23.
go back to reference Elliot SJ, Striker LJ, Stetler-Stevenson WG, Jacot TA, Striker GE (1999) Pentosan polysulfate decreases proliferation and net extracellular matrix production in mouse mesangial cells. J Am Soc Nephrol 10:62–68PubMed Elliot SJ, Striker LJ, Stetler-Stevenson WG, Jacot TA, Striker GE (1999) Pentosan polysulfate decreases proliferation and net extracellular matrix production in mouse mesangial cells. J Am Soc Nephrol 10:62–68PubMed
24.
go back to reference Stracke H, Lindemann A, Federlin K (1996) A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy. Exp Clin Endocrinol Diabetes 104:311–316PubMedCrossRef Stracke H, Lindemann A, Federlin K (1996) A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy. Exp Clin Endocrinol Diabetes 104:311–316PubMedCrossRef
25.
go back to reference Ziegler D, Gries FA (1997) Alpha-lipoic acid treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes 46:S62–S66PubMed Ziegler D, Gries FA (1997) Alpha-lipoic acid treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes 46:S62–S66PubMed
26.
go back to reference Ametov AS, Barinov A, Dyck PJ, Hermann R, Kozlova N, Litchy WJ, Low PA, Nehrdich D, Novosadova M, O’Brien PC, Reljanovic M, Samigullin R, Schuette K, Strokov I, Tritschler H, Yakhno N, Ziegler D (2003) The sensory symptoms of diabetic polyneuropathy are improved with α-lipoic acid: the SYDNEY trial. Diabetes Care 26:770–776PubMedCrossRef Ametov AS, Barinov A, Dyck PJ, Hermann R, Kozlova N, Litchy WJ, Low PA, Nehrdich D, Novosadova M, O’Brien PC, Reljanovic M, Samigullin R, Schuette K, Strokov I, Tritschler H, Yakhno N, Ziegler D (2003) The sensory symptoms of diabetic polyneuropathy are improved with α-lipoic acid: the SYDNEY trial. Diabetes Care 26:770–776PubMedCrossRef
27.
go back to reference Ewing DJ, Martyn CN, Young RJ, Clarke BF (1985) The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care 8:491–498PubMedCrossRef Ewing DJ, Martyn CN, Young RJ, Clarke BF (1985) The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care 8:491–498PubMedCrossRef
28.
go back to reference Ziegler D (1994) Diabetic cardiovascular autonomic neuropathy: prognosis, diagnosis and treatment. Diabetes Metab Rev 10:339–383PubMed Ziegler D (1994) Diabetic cardiovascular autonomic neuropathy: prognosis, diagnosis and treatment. Diabetes Metab Rev 10:339–383PubMed
29.
go back to reference Cohen KL, Lucibello FE, Chomiak M (1990) Lack of effect of clonidine and pentoxifylline in short-term therapy of diabetic peripheral neuropathy. Diabetes Care 13:1074–1077PubMedCrossRef Cohen KL, Lucibello FE, Chomiak M (1990) Lack of effect of clonidine and pentoxifylline in short-term therapy of diabetic peripheral neuropathy. Diabetes Care 13:1074–1077PubMedCrossRef
30.
go back to reference Lee Y, Robinson M, Wong N, Chan E, Charles MA (1997) The effect of pentoxifylline on current perception thresholds in patients with diabetic sensory neuropathy. J Diabetes Complications 11:274–278PubMedCrossRef Lee Y, Robinson M, Wong N, Chan E, Charles MA (1997) The effect of pentoxifylline on current perception thresholds in patients with diabetic sensory neuropathy. J Diabetes Complications 11:274–278PubMedCrossRef
31.
go back to reference Cohen SM, Mathews T (1991) Pentoxifylline in the treatment of distal diabetic neuropathy. Angiology 42:741–746PubMedCrossRef Cohen SM, Mathews T (1991) Pentoxifylline in the treatment of distal diabetic neuropathy. Angiology 42:741–746PubMedCrossRef
32.
go back to reference Rendell M, Bamisedun O (1992) Skin blood flow and current perception in pentoxifylline-treated diabetic neuropathy. Angiology 43:843–851PubMedCrossRef Rendell M, Bamisedun O (1992) Skin blood flow and current perception in pentoxifylline-treated diabetic neuropathy. Angiology 43:843–851PubMedCrossRef
33.
go back to reference Wirta OR, Pasternack AI, Mustonen JT, Laippala PJ, Reinikainen PM (1999) Urinary albumin excretion rate is independently related to autonomic neuropathy in type 2 diabetes mellitus. J Intern Med 245:329–335PubMedCrossRef Wirta OR, Pasternack AI, Mustonen JT, Laippala PJ, Reinikainen PM (1999) Urinary albumin excretion rate is independently related to autonomic neuropathy in type 2 diabetes mellitus. J Intern Med 245:329–335PubMedCrossRef
34.
go back to reference Rodriguez-Morán M, González-González G, Bermúdez-Barba MV, Medina de la Garza CE, Tamez-Pérez HE, Martínez-Martínez FJ, Guerrero-Romero F (2006) Effects of pentoxifylline on the urinary protein excretion profile of type 2 diabetic patients with microproteinuria: a double-blind, placebo-controlled randomized trial. Clin Nephrol 66:3–10PubMed Rodriguez-Morán M, González-González G, Bermúdez-Barba MV, Medina de la Garza CE, Tamez-Pérez HE, Martínez-Martínez FJ, Guerrero-Romero F (2006) Effects of pentoxifylline on the urinary protein excretion profile of type 2 diabetic patients with microproteinuria: a double-blind, placebo-controlled randomized trial. Clin Nephrol 66:3–10PubMed
35.
go back to reference Solerte SB, Fioravanti M, Bozzetti A, Schifino N, Patti AL, Fedele P, Viola C, Ferrari E (1986) Pentoxifylline, albumin excretion rate and proteinuria in type I and type II diabetic patients with microproteinuria: results of a short-term randomized study. Acta Diabetol Lat 23:171–177PubMedCrossRef Solerte SB, Fioravanti M, Bozzetti A, Schifino N, Patti AL, Fedele P, Viola C, Ferrari E (1986) Pentoxifylline, albumin excretion rate and proteinuria in type I and type II diabetic patients with microproteinuria: results of a short-term randomized study. Acta Diabetol Lat 23:171–177PubMedCrossRef
Metadata
Title
Effects of pentoxifylline and pentosan polysulphate combination therapy on diabetic neuropathy in type 2 diabetes mellitus
Authors
Boglárka Laczy
Judit Cseh
Márton Mohás
Lajos Markó
Mónika Tamaskó
Tamás Kőszegi
Gergő A. Molnár
Zoltán Wagner
László Wagner
István Wittmann
Publication date
01-06-2009
Publisher
Springer Milan
Published in
Acta Diabetologica / Issue 2/2009
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-008-0064-5

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