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METHOD FOR ASSESSING A DIABETIC'S RISK OF EXPERIENCING A DIABETES-ASSOCIATED PATHOLOGIC CONDITION

机译:评估患糖尿病相关病情的糖尿病风险的方法

摘要

Disclosed is a class of compounds which inhibit the enzymatic conversion of fructose-lysine into fructose-lysine-3-phosphate in an ATP dependent reaction in a newly discovered metabolic pathway. According to the normal functioning on this pathway, fructose-lysine-3-phosphate (FL3P) is broken down to form free lysine, inorganic phosphate and 3-deoxyglucosone (3DG), the latter being a reactive protein modifying agent. 3DG can be detoxified by reduction to 3-deoxyfructose (3DF), or it can react with endogenous proteins to form advanced glycation end-product modified proteins (AGE-proteins), which are believed to be a contributing cause of diabetic complications. Also disclosed are therapeutic methods of using such inhibitors to reduce formation of AGE-proteins and thereby lessen, reduce and delay diabetic complications, as well as methods for assessing a diabetic's risk of developing complications and for determining the efficacy of the disclosed inhibitor therapy by measuring the ratio of 3DG to 3DF in a biological sample following an oral dose of a fructose-lysine-containing food product.
机译:公开了一类化合物,其在新发现的代谢途径中以ATP依赖性反应抑制果糖-赖氨酸的酶促转化为果糖-赖氨酸-3-磷酸。根据该途径的正常功能,将果糖-3-磷酸赖氨酸(FL3P)分解形成游离赖氨酸,无机磷酸和3-脱氧葡糖酮(3DG),后者是一种反应性蛋白质修饰剂。 3DG可以通过还原为3-脱氧果糖(3DF)来解毒,或者可以与内源性蛋白质反应形成高级糖基化终产物修饰的蛋白质(AGE-蛋白质),据信这是糖尿病并发症的一个起因。还公开了使用此类抑制剂减少AGE蛋白形成并由此减少,减少和延迟糖尿病并发症的治疗方法,以及通过测量糖尿病来评估糖尿病发生并发症的风险和确定所公开的抑制剂疗法的功效的方法。口服含果糖赖氨酸的食品后,生物样品中3DG与3DF的比例。

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