Induction and Activities of Pyruvate Dehydrogenase and α-ketoglutarate Dehydrogenase in Type 2 Diabetic Patients and Therapy with Vitamin B1

Abstract

Aims/Introduction: Thiamine deficiency in diabetes mellitus may impair the function of thiamine pyrophosphate dependent enzymes pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase complexes (α KGD) resulting in renal dysfunction. This study was designed to investigate the effect of high dose thiamine therapy on the expression and activities of PDH and α KGH in such patients. Materials and Methods: 125 patients with type 2 diabetes and microalbuminuria were assessed for enrollment in a randomized, double blind placebo controlled clinical trial for 5 months. 40 Patients fulfilling the requisite criteria were divided into two groups, one treated with 300mg/day thiamine and the other group was administered placebo. Fifty normal healthy controls were included in the study only for baseline estimation of the parameters. Results: The enrolled patients with type 2 diabetes showed decreased activities of mononuclear enzymes as compared to the healthy controls. Q-PCR study showed that the expression levels of the genes encoding PDE1β and α KGDE1k were significantly reduced in the patients with type 2 diabetes as compared to the healthy controls. Thiamine therapy resulted in significant increases in the expression of PDE1β and α KGDE1 genes, which persisted even 2 months after the washout. Thiamine therapy therefore resulted in significant increase in activities of these enzymes and incremental activity persisted into the washout period. Conclusion: These results indicate that the thiamine acts as an inducer in the expression of mononuclear PDH and α KGD thus enhancing their activities in the type 2 diabetes patients with incipient nephropathy. It was internationally registered with the South Asian Clinical Trials Registry based in India as CTRI/2008/091/000112 and with the World Health Organization’s (WHO) International clinical trials registry Platform search portal http://www.ctri.in/Clinicaltrials/ViewTrial.jsp?trialno=203