Abstract
Background: Traditional and more recently, a host of nontraditional risk factors of type 2 diabetes mellitus have adopted significance as promoters of the pathologies associated with this disease. High dose Vitamin B1 (thiamine) has been found at preclinical level to play an ameliorative role through a number of intracellular metabolic pathways. In order to demonstrate this clinically, pioneering research on the effect of high dose thiamine on associated markers of biochemical dysfunction, incipient diabetic nephropathy, hemostasis (plasminogen activation inhibitor/PAI-1), oxidative stress (plasma thiols) and second messenger signaling (protein kinase C/ PKC ) was conducted. Subjects and methods: Type 2 diabetics were enrolled in randomized, double blind placebo controlled clinical trial for 6 months. Patients were divided into two groups and administered 300 mg/day thiamine or placebo for 3 months, followed by a 2 month washout period. Normal healthy controls participated for baseline estimations only. Plasma and urinary thiamine levels, microalbuminuria, PAI-1, oxidative stress marker plasma thiols were estimated. The messenger signaling PKC profile was determined in normal controls and in type 2 diabetics. Results: Lower plasma thiamine concentration of diabetic patients was observed as compared to normal subjects. Thiamine treatment increased thiamine concentration and urinary thiamine excretion and reduced significantly microalbuminuria and glycated hemoglobin. Type 2 diabetics had significantly higher PAI-1 and PKC levels as compared to normal controls. Following 3 months thiamine therapy, PAI-1 remained unchanged, while levels of PKC were reduced significantly in thiamine treated diabetics and lowered after discontinuing the drug. While in placebo group significant increase in PKC levels persisted during the whole period. Oxidative stress marker, plasma thiols was reduced significantly in diabetics versus normal controls with no change occurring following thiamine or placebo therapy. Conclusion: Thiamine therapy significantly improved micoalbuminuria, glycated hemoglobin, thiamine status and decreased PKC levels with no significant impact on oxidative stress and fibrinolysis profile.
Highlights
Traditional and more recently, a host of nontraditional risk factors of type 2 diabetes mellitus have adopted significance as promoters of the pathologies associated with this disease
The baseline demographic, physiologic and biochemical characteristics, thiamine and microalbuminuria levels of normal healthy controls and type 2 diabetic patients recruited for this study and randomized in the placebo and thiamine treatment arms are given in (Table 1) and elucidated below
Urinary albumin excretion in mg/24 hrs was significantly higher in the type 2 diabetics of both thiamine (53.86 ± 22.62) mg/24 hrs and placebo groups (55.74 ± 23.71) mg/24 hrs as compared to controls (7.968 ± 5.07) mg/24 hrs
Summary
Traditional and more recently, a host of nontraditional risk factors of type 2 diabetes mellitus have adopted significance as promoters of the pathologies associated with this disease. In order to demonstrate this clinically, pioneering research on the effect of high dose thiamine on associated markers of biochemical dysfunction, incipient diabetic nephropathy, hemostasis (plasminogen activation inhibitor/PAI-1), oxidative stress (plasma thiols) and second messenger signaling (protein kinase C/ PKC ) was conducted. PKC has been associated with vascular alterations such as increases in permeability, contractility, extracellular matrix synthesis, cell growth and apoptosis, angiogenesis, leukocyte adhesion, and cytokine activation and inhibition [6]. These perturbations in vascular cell homeostasis caused by different PKC isoforms (PKC-α, -β1/2, and PKC-δ) are linked to the development of pathologies affecting large vessel (atherosclerosis, cardiomyopathy) andsmallvessel (retinopathy, nephropathyandneuropathy) complications [7,8,9]
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