Prevention of incipient diabetic nephropathy by high dose thiamine and Benfotiamine
Written by Paul Thornalley.
(This contribution is based on extracts from the recent paper by the author and co-workers: Babaei-Jadidi, R., Karachalias, N., Ahmed, N., Battah, S., and Thornalley, P. J. Prevention of incipient diabetic nephropathy by high dose thiamine and Benfotiamine. Diabetes 52, 2110-2120, 2003)
Nephropathy is a common complication of diabetes mellitus associated with a high risk of cardiovascular disease and mortality. Studies from my research team showed recently that stimulation of the reductive pentosephosphate pathway by therapy with thiamine and the thiamine monophosphate derivative Benfotiamine at high dose (7 and 70 mg/kg) prevented the development of incipient nephropathy in experimental diabetes. Diabetes was associated with mild thiamine deficiency and decreased expression of the thiamine pyrophosphate-dependent enzyme transketolase. High dose thiamine and Benfotiamine therapy increased transketolase expression in renal glomeruli, activating the reductive pentosephosphate pathway and increasing the conversion of triosephosphates to ribose-5-phosphate. This was associated with decreased glomerular protein kinase C activity, protein glycation and oxidative stress - three major pathways of biochemical dysfunction in hyperglycemia, and potent inhibition of the development of microalbuminuria. Benfotiamine also inhibited diabetes-induced hyperfiltration. This was achieved without change in elevated plasma glucose concentration and glycated haemoglobin in the diabetic state. High dose thiamine and Benfotiamine therapy is a potential novel strategy for the prevention of clinical diabetic nephropathy.
Next page: Introduction: Diabetes and Nephropathy