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Published in: Diabetologia 10/2008

01-10-2008 | Short Communication

Oral benfotiamine plus α-lipoic acid normalises complication-causing pathways in type 1 diabetes

Authors: X. Du, D. Edelstein, M. Brownlee

Published in: Diabetologia | Issue 10/2008

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Abstract

Aims/hypothesis

We determined whether fixed doses of benfotiamine in combination with slow-release α-lipoic acid normalise markers of reactive oxygen species-induced pathways of complications in humans.

Methods

Male participants with and without type 1 diabetes were studied in the General Clinical Research Centre of the Albert Einstein College of Medicine. Glycaemic status was assessed by measuring baseline values of three different indicators of hyperglycaemia. Intracellular AGE formation, hexosamine pathway activity and prostacyclin synthase activity were measured initially, and after 2 and 4 weeks of treatment.

Results

In the nine participants with type 1 diabetes, treatment had no effect on any of the three indicators used to assess hyperglycaemia. However, treatment with benfotiamine plus α-lipoic acid completely normalised increased AGE formation, reduced increased monocyte hexosamine-modified proteins by 40% and normalised the 70% decrease in prostacyclin synthase activity from 1,709 ± 586 pg/ml 6-keto-prostaglandin F to 4,696 ± 533 pg/ml.

Conclusions/interpretation

These results show that the previously demonstrated beneficial effects of these agents on complication-causing pathways in rodent models of diabetic complications also occur in humans with type 1 diabetes.
Trial registration: NCT00703989
Funding: Juvenile Diabetes Research Foundation grant 8-2003-784 and GCRC grant MO1-RR12248.
Literature
1.
go back to reference Hammes H-P, Du X, Edelstein D et al (2003) Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med 9:294–299PubMedCrossRef Hammes H-P, Du X, Edelstein D et al (2003) Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med 9:294–299PubMedCrossRef
2.
go back to reference Babaei-Jadidi R, Karachalias N, Ahmed N, Battah S, Thornalley PJ (2003) Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine. Diabetes 52:2110–2120PubMedCrossRef Babaei-Jadidi R, Karachalias N, Ahmed N, Battah S, Thornalley PJ (2003) Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine. Diabetes 52:2110–2120PubMedCrossRef
3.
go back to reference Berrone E, Beltramo E, Solimine C, Ape AU, Porta M (2006) Regulation of intracellular glucose and polyol pathway by thiamine and benfotiamine in vascular cells cultured in high glucose. J Biol Chem 281:9307–9313PubMedCrossRef Berrone E, Beltramo E, Solimine C, Ape AU, Porta M (2006) Regulation of intracellular glucose and polyol pathway by thiamine and benfotiamine in vascular cells cultured in high glucose. J Biol Chem 281:9307–9313PubMedCrossRef
4.
go back to reference Lin J, Bierhaus A, Bugert P et al (2006) Effect of R-(+)-alpha-lipoic acid on experimental diabetic retinopathy. Diabetologia 49:1089–1096PubMedCrossRef Lin J, Bierhaus A, Bugert P et al (2006) Effect of R-(+)-alpha-lipoic acid on experimental diabetic retinopathy. Diabetologia 49:1089–1096PubMedCrossRef
5.
go back to reference Yi X, Maeda N (2006) alpha-Lipoic acid prevents the increase in atherosclerosis induced by diabetes in apolipoprotein E-deficient mice fed high-fat/low-cholesterol diet. Diabetes 55:2238–2244PubMedCrossRef Yi X, Maeda N (2006) alpha-Lipoic acid prevents the increase in atherosclerosis induced by diabetes in apolipoprotein E-deficient mice fed high-fat/low-cholesterol diet. Diabetes 55:2238–2244PubMedCrossRef
6.
go back to reference Yao D, Taguchi T, Matsumura T et al (2007) High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A. J Biol Chem 282:31038–31045PubMedCrossRef Yao D, Taguchi T, Matsumura T et al (2007) High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A. J Biol Chem 282:31038–31045PubMedCrossRef
7.
go back to reference Zachara NE, Hart GW, Cole RN, Gao Y (2002) Detection and analysis of proteins modified by O-linked N-acetylglucosamine. In: Current protocols in protein science. John Wiley, New York, chapter 17, unit 17.6 Zachara NE, Hart GW, Cole RN, Gao Y (2002) Detection and analysis of proteins modified by O-linked N-acetylglucosamine. In: Current protocols in protein science. John Wiley, New York, chapter 17, unit 17.6
8.
go back to reference Du X, Edelstein D, Obici S, Higham N, Zou M-H, Brownlee M (2006) Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation. J Clin Invest 116:1071–1080PubMedCrossRef Du X, Edelstein D, Obici S, Higham N, Zou M-H, Brownlee M (2006) Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation. J Clin Invest 116:1071–1080PubMedCrossRef
9.
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
10.
go back to reference Zou MH, Shi C, Cohen RA (2002) High glucose via peroxynitrite causes tyrosine nitration and inactivation of prostacyclin synthase that is associated with thromboxane/prostaglandin H(2) receptor-mediated apoptosis and adhesion molecule expression in cultured human aortic endothelial cells. Diabetes 51:198–203PubMedCrossRef Zou MH, Shi C, Cohen RA (2002) High glucose via peroxynitrite causes tyrosine nitration and inactivation of prostacyclin synthase that is associated with thromboxane/prostaglandin H(2) receptor-mediated apoptosis and adhesion molecule expression in cultured human aortic endothelial cells. Diabetes 51:198–203PubMedCrossRef
Metadata
Title
Oral benfotiamine plus α-lipoic acid normalises complication-causing pathways in type 1 diabetes
Authors
X. Du
D. Edelstein
M. Brownlee
Publication date
01-10-2008
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 10/2008
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-008-1100-2

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