Article

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

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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.

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... Thiamine (vitamin B1) is a water-soluble vitamin and an essential normal dietary component [4]. Thiamine deficiency exists in both type 1 and type 2 diabetes patients [5] and in patients with type 2 diabetes and microalbuminuria [6][7][8][9]. Thiamine and benfotiamine therapy prevents the development of microvascular complications in experimental diabetes [10][11] and could possibly also have a beneficial role to play in the treatment of type 2 diabetes mellitus [5]. ...
... Based on the above evidence a novel strategy to counter biochemical dysfunction linked to the development of diabetic nephropathy is highdose thiamine therapy. In our previous published pilot study, we evaluated the effect of oral high dose supplements of thiamine on urinary albumin excretion (UAE), a marker of early-stage diabetic nephropathy, in type 2 diabetic patients with microalbuminuria and an improvement in microalbuminuria and transketolase levels [6,9]. AKDH and PDH are both thiamine dependent enzymes as well, required for effective utilization of the glucose intracellularly in all tissues including the kidney and in generation of ATP for all processes including renal function. ...
... Our research on activity and expression analysis of PDE1 and alphaketoglutarate dehydrogenase in mononuclear cells revealed continued increment of both activity and expression levels of these enzymes after 3 months of high dose thiamine therapy and its persistence even 2 months after stoppage of therapy. The mean baseline plasma thiamine levels of the diabetic patients were found to be directly proportional to their enzyme activities and expression levels i.e both showed improvement with thiamine therapy [6][7][8][9]. ...
... Transketolase plays a fundamental role in intracellular glucose metabolism by shifting excess F-6-P from glycolysis into the pentose phosphate pathway, thereby preventing activation of the hexosamine pathway and decreasing methylglyoxal formation as described above (Beltramo et al., 2008). Patients with diabetes show a high prevalence of thiamine and transketolase deficiency (Thornalley et al., 2007;Alam et al., 2011), and high doses of thiamine in combination with pyridoxine (vitamin B 6 ) improved neuropathic symptoms in patients with diabetes who have DPN (Abbas and Swai, 1997). ...
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Thiamine in diabetic nephropathy: a novel treatment modality? A Double-blind, Randomized, Placebo-controlled clinical trail on benfotiamine treatment in patients with diabetic nephropathy
  • A Alkhalaf
  • N Kleefstra
  • Kh Groenier
  • Sjl Bakker
  • G Navis
  • Bilo
Alkhalaf A, Kleefstra N, Groenier KH, Bakker SJL, Navis G, Bilo HGJ(2010). Thiamine in diabetic nephropathy: a novel treatment modality? A Double-blind, Randomized, Placebo-controlled clinical trail on benfotiamine treatment in patients with diabetic nephropathy. Diabetes Care, 33 (7): 1598-1601