Effect of high dose thiamine therapy on activity and molecular aspects of transketolase in Type 2 diabetic patients

Abstract

Commonest form of diabetes mellitus is Type 2, treated with oral hypoglycemic agents, which often carry potential adverse effects and do not address the intracellular metabolism of glucose. Thiamine is an essential co-factor for vital subcellular enzymes and has potential to benefit Type 2 diabetics. This study was therefore designed to investigate the effect of high dose thiamine therapy on the activity and molecular aspects of transketolase in Type 2 diabetic patients. Over 100 Type 2 microalbuminuric diabetics were enrolled in a randomized, double blind placebo controlled clinical trial for 6 months. Patients were divided into two groups, one treated with 300 mg/day thiamine and the other group was administered placebo for a period of 3 months followed by a 2 month washout period. 50 normal healthy controls participated for baseline estimations only. Transketolase activity of mononuclear cells and erythrocytes were determined. Also q-polymerase chain reaction (PCR) was used to determine expression levels of transketolase gene in mononuclear cells. All enrolled Type 2 diabetics had > 40% lower mononuclear transketolase activity as compared to healthy individuals. Thiamine therapy for three months resulted in a 65% significant increase in transketolase activity which persisted into washout period. Mononuclear transketolase gene expression was significantly reduced in Type 2 diabetics as compared to normal controls (0.66 fold thiamine group) and (0.89 fold) placebo group). High dose thiamine therapy resulted in highly significant increase (2.86 fold) in expression of transketolase gene in mononuclear cells which was sustained at 2.91 fold after washout period. These results indicate that high dose thiamine therapy improves both transketolase activity and expression in Type 2 diabetic patients with incipient nephropathy.

Key words: Diabetes mellitus Type 2, thiamine, transketolase, mononuclear cells, erythrocytes, qRT-PCR.