Transketolase activators as a novel therapy: their significance in the pathogenesis and treatment of diabetic microvascular complications

Main Article Content

K. Singh
T. Yuzvenko
D. Kogut


The review article presents an analysis of the literature on the effect of thiamine and its derivatives on the metabolism in cells and its role in the pathogenesis of complications of diabetes mellitus. The features of the conversion of an inactive form that enters the human body with food and drugs into the active form of thiamine are considered. The metabolic pathways of thiamine and its derivatives are also clarified. The article describes the features of allithiamine and the practical importance of its metabolism in cells for the treatment of complications of diabetes mellitus, in particular, diabetic polyneuropathy. The data in this article will help clinicians understand the relevance and necessity of using drugs containing thiamine in their practice.

Article Details

How to Cite
Singh, K., T. Yuzvenko, and D. Kogut. “Transketolase Activators As a Novel Therapy: Their Significance in the Pathogenesis and Treatment of Diabetic Microvascular Complications”. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), vol. 15, no. 7, Dec. 2019, pp. 576-9, doi:10.22141/2224-0721.15.7.2019.186062.
Literature Review


Emerging Risk Factors Collaboration, N, Gao P, Seshasai SR, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Emerging Risk Factors Collaboration. Lancet. 2010 Jun 26;375(9733):2215-22. doi: 10.1016/S0140-6736(10)60484-9.

Kaiser N, Sasson S, Feener EP, et al. Differential regulation of glucose transport and transporters by glucose in vascular endothelial and smooth muscle cells. Diabetes. 1993;42(1):80-89. doi: 10.2337/diab.42.1.80.

Heilig CW, Concepcion LA, Riser BL, Freytag SO, Zhu M, Cortes P. Overexpression of glucose transporters in rat mesangial cells cultured in a normal glucose milieu mimics the diabetic phenotype. J Clin Invest. 1995 Oct;96(4):1802-14. doi: 10.1172/JCI118226.

Brownlee M. The pathobiology of diabetic complications, a unifying mechanism. Diabetes. 2005 Jun;54(6):1615-25. doi: 10.2337/diabetes.54.6.1615.

Fowler MJ. Microvascular and Macrovascular Complications of Diabetes. Clinical Diabetes. 2008;26(2):77-82. doi: 10.2337/diaclin.26.2.77.

Du XL, Edelstein D, Rossetti L, et al. Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12222-6. doi:10.1073/pnas.97.22.12222.

Dyck PJ, Kratz KM, Karnes JL, et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology. 1993;43(4):817-24. doi: 10.1212/wnl.43.4.817.

Tesfaye S, Boulton AJ, Dyck PJ, et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010;33(10):2285-93. doi: 10.2337/dc10-1303.

Vamos EP, Bottle A, Edmonds ME, Valabhji J, Majeed A, Millett C. Trends in lower extremity amputations in people with and without diabetes in England. 1996-2005. Diabetes Res Clin Pract. 2010;87(2):275-82. doi: 10.1016/j.diabres.2009.11.016.

Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005 Jan 12;293(2):217-28. doi: 10.1001/jama.293.2.217.

Llewelyn JG, Tomlinson DR, Thomas PK. Diabetic Neuropathies. In: Dyck PJ, Thomas, PK, editors. Peripheral Neuropathy. 4th Edition. Philadelphia: Elsevier; 2005. 1951-1992 pp.

Dyck PJ. Severity and staging of diabetic polyneuropathy. In: Gries FA, Cameron NE, Low PA, Ziegler D, editors. Textbook of Diabetic Neuropathy. Stuttgart, Thieme; 2003. 170-175 рр.

Dyck PJ, Overland CJ, Low PA, et al. Signs and symptoms versus nerve conduction studies to diagnose diabetic sensorimotor polyneuropathy: Cl vs. NPhys trial. Muscle Nerve. 2011;42(2):157-64. doi: 10.1002/mus.21661.

Boulton AJM, Malik RA, Arezzo JC, Sosensko JM. Diabetic Somatic neuropathies. Diabetes Care. 2004;27(6):1458–78. doi: 10.2337/diacare.27.6.1458.

Boulton AJ, Vinik AI, Arezzo JC, et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005;28(4):956-962. doi: 10.2337/diacare.28.4.956.

Hammes HP, Du X, Edelstein D, et al. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med. 2003(3);9:294-299. doi:10.1038/nm834.

Rote Liste, 2008. Fachinfo-Service, Fach informations verzeichnis Deutschland (einschlieslich EU-Zulassungen), Verlag Rote Liste Service GmbH, Frankfurt/Main.

Volvert ML, Seyen S, Piette M, et al. Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives. BMC Pharmacol. 2008 Jun 12;8:10. doi: 10.1186/1471-2210-8-10.

Loew D. Pharmacokinetics of thiamine derivatives especially of benfotiamine. Int J Clin Pharmacol Ther. 1996 Feb;34(2):47-50. doi: 10.1186/1471-2210-8-10.

Hammes HP, Du X, Edelstein D, et al. Benfothaimine blocks three major pathways of hyperglycemic damage and prevents experimental diabetes. Nat Med. 2003 Mar;9(3):294-9. doi: 10.1038/nm834.

Beltramo E, Berrone E, Buttiglieri S, Porta M. Thiamine and benfothiamine prevent increased apoptosis in endothelial cells and pericytes cultured in high glucose. Diabetes Metab Res Rev. 2004 Jul-Aug;20(4):330-6. doi:10.1002/dmrr.470.