High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study

Rabbani, Naila; Alam, Saadia Shahzad; Riaz, Saira; Larkin, James R.; Akhtar, Mehwish; Shafi, Tahir; Thornalley, Paul J.

doi:10.1007/s00125-008-1224-4

Cited by 149 publications

(129 citation statements)

References 9 publications

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“…High-dose therapy with thiamine and the thiamine monophosphate (TMP) derivative benfotiamine prevented the development of microvascular complications in experimental diabetes [3][4][5]. A pilot-scale trial of type 2 diabetic patients with incipient nephropathy (microalbuminuria) showed that high-dose thiamine therapy improved renal function and induced regression of microalbuminuria [6,7]. Further understanding of how thiamine supplementation prevents incipient nephropathy and other microvascular complications is now required.…”

Section: Introductionmentioning

confidence: 99%

Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes

et al. 2010

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Aims/hypothesis The aim of this study was to quantify protein damage by glycation, oxidation and nitration in a rat model of diabetes at the sites of development of microvascular complications, including the effects of thiamine and benfotiamine therapy. Methods Diabetes was induced in male Sprague-Dawley rats by 55 mg/kg streptozotocin and moderated by insulin (2 U twice daily). Diabetic and control rats were given thiamine or benfotiamine (7 or 70 mg kg −1 day −1 ) over 24 weeks. Plasma, urine and tissues were collected and analysed for protein damage by stable isotopic dilution analysis MS. Results There were two-to fourfold increases in fructosyllysine and AGE content of glomerular, retinal, sciatic nerve and plasma protein in diabetes. Increases in AGEs were reversed by thiamine and benfotiamine therapy but increases in fructosyl-lysine were not. Methionine sulfoxide content of plasma protein and 3-nitrotyrosine content of sciatic nerve protein were increased in diabetes. Plasma glycation free adducts were increased up to twofold in diabetes; the increases were reversed by thiamine. Urinary excretion of glycation, oxidation and nitration free adducts was increased by seven-to 27-fold in diabetes. These increases were reversed by thiamine and benfotiamine therapy. Conclusions/interpretation AGEs, particularly argininederived hydroimidazolones, accumulate at sites of microvascular complication development and have markedly increased urinary excretion rates in experimental diabetes. Thiamine and benfotiamine supplementation prevented tissue accumulation and increased urinary excretion of protein glycation, oxidation and nitration adducts. Similar effects may contribute to the reversal of early-stage clinical diabetic nephropathy by thiamine.

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Section: Introductionmentioning

confidence: 99%

Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes

et al. 2010

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“…For survival of these patients insulin is not necessary.In these patients obesity is a major cause of insulin resistance while increase age and physical inactivity are also important factors.Ketoacidosis occur because of stress of other infection. it has strong genetic predisposition (Riaz, S. 2009). …”

Section: Type 2 Diabetesmentioning

confidence: 99%

“…While prevalence of hypertension in type 2 diabetic patients is estimated at 50% with one estimated as high as 74%. (Riaz, S et al 2009) …”

Section: Prevalence Of Diabetic Hypertensive Nephropthymentioning

confidence: 99%

Study of Diabetic Hypertensive Nephropathy in the Local Population of Pakistan

Riaz¹,

Alam²

2012

Diabetic Nephropathy

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“…The application of benfotiamine and the resulting activation of the enzyme transketolase in the diabetic, hyperglycemic system can also produce beneficial effects on general nerve health. Benfotiamine has been shown in many preclinical [21,[31][32][33][34][35][36][37][38][39][40][41][42][43] as well as clinical studies [44][45][46][47][48][49][50][51][52][53][54][55][56][57] to prevent the formation of AGEs [21,53] and eventually with continued treatment to reverse the symptoms associated with the neuropathy [46,47,52,57]. By increasing intracellular levels of thiamine, benfotiamine indirectly induces enzymatic and biochemical pathways [58][59][60] through elevated concentrations of thiamine diphosphate resulting in a reduced level of damaging glucose-derived chemical protein species [21,22,32,[37][38][39][60][61]…”

Section: Introductionmentioning

confidence: 99%

Efficient Transdermal Delivery of Benfotiamine in an Animal Model

2015

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We designed a transdermal system to serve as a delivery platform for benfotiamine utilizing the attributes of passive penetration enhancing molecules to penetrate through the outer layers of skin combined with the advance of incorporating various peripherally-acting vasodilators to enhance drug uptake. Benfotiamine, incorporated into this transdermal formulation, was applied to skin in an animal model in order to determine the ability to deliver this thiamine pro-drug effectively to the sub-epithelial layers. In this proof of concept study in guinea pigs, we found that a single topical application of either a solubilized form of benfotiamine (15 mg) or a microcrystalline suspension form (25 mg) resulted in considerable increases of the dephosphorylated benfotiamine (S-benzoylthiamine) in the skin tissue as well as in significant increases in the thiamine and thiamine phosphate pools compared to control animals. The presence of a ~8000x increase in thiamine and increases in its phosphorylated derivatives in the epidermis

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High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study

Abstract: Pakistan Higher Education Commission.

Cited by 149 publications

References 9 publications

Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes

Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes

Study of Diabetic Hypertensive Nephropathy in the Local Population of Pakistan

Efficient Transdermal Delivery of Benfotiamine in an Animal Model

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