This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The investigators seek to determine the effects of benfotiamine, a thiamine derivative, and alpha lipoic acid (both of which are dietary substances) on measurable, short-term markers of endothelial function: PGP-1-alpha, 3-nitrotyrosine modified albumin, and forefinger blood flow in response to hypoxia. The overall hypothesis is that vascular damage due to intracellular hyperglycemia in type 1 diabetes is due to preferential shunting of glucose through non-oxidative metabolic pathways, leading to accumulation of harmful superoxides and inflammatory molecules, and that dietary supplementation with benfotiamine will block hyperglycemic non-oxidative damage by increasing transketolase activity, and alpha lipoic acid will block NF-kapa-beta accumulation within cells. The substances will be administered both separately and together for a 28 day period of time. There will be a baseline assessment, a 15 day assessment and a 28 day assessment with a blood draw and measurement of forefinger blood flow.
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