Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine.

Abstract:

:Accumulation of triosephosphates arising from high cytosolic glucose concentrations in hyperglycemia is the trigger for biochemical dysfunction leading to the development of diabetic nephropathy-a common complication of diabetes associated with a high risk of cardiovascular disease and mortality. Here we report that stimulation of the reductive pentosephosphate pathway by high-dose therapy with thiamine and the thiamine monophosphate derivative benfotiamine countered the accumulation of triosephosphates in experimental diabetes and inhibited the development of incipient nephropathy. High-dose thiamine and benfotiamine therapy increased transketolase expression in renal glomeruli, increased the conversion of triosephosphates to ribose-5-phosphate, and strongly inhibited the development of microalbuminuria. This was associated with decreased activation of protein kinase C and decreased protein glycation and oxidative stress-three major pathways of biochemical dysfunction in hyperglycemia. Benfotiamine also inhibited diabetes-induced hyperfiltration. This was achieved without change in elevated plasma glucose concentration and glycated hemoglobin in the diabetic state. High-dose thiamine and benfotiamine therapy is a potential novel strategy for the prevention of clinical diabetic nephropathy.

journal_name

Diabetes

journal_title

Diabetes

authors

Babaei-Jadidi R,Karachalias N,Ahmed N,Battah S,Thornalley PJ

doi

10.2337/diabetes.52.8.2110

subject

Has Abstract

pub_date

2003-08-01 00:00:00

pages

2110-20

issue

8

eissn

0012-1797

issn

1939-327X

journal_volume

52

pub_type

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