Modification of Biochemical Derangements and VEGF Secretion May Prevent Diabetic Retinopathy (DR): An Advance Study

L. Mondal, Subhasish Pramanik, Sriparna De, Suman K Paine, G. Bhaduri
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引用次数: 3

Abstract

Unutilized, enormous intracellular glucose in insulin-nondependent tissues, including retina, leads to several consequences: (i) increased formation of advanced glycation end products, (ii) activation of polyol pathway, (iii) anaerobic glycolysis, (iv) glutamate toxicity, (v) lipid peroxidation and oxidative stress, and all of these, finally, resulting in convergence to up regulation of antigenic VEGF and VEGFR2, the crucial player in the development of DR. The purpose of the present pilot study is to assess the effects of one kind of intervention on the development of DR: supplementation of B-vitamins (B1, B2, B3, B5 and B6), vitamin C and vitamin E on amelioration of biochemical derangements related to development of DR. 400 diagnosed type 2 diabetic patients were identified for the study, of which subjects were randomised 1:1 to receive oral antidiabetic medication along with B-vitamins, vitamin C and vitamin E or only antidiabetic medication to give the study and controlled population in this unblended randomized trial since December 2004 to December 2017. The following preliminary tasks were completed: firstly, baseline detailed fundoscopic examinations were enough to exclude the presence of retinopathy. Secondly, had baseline biochemical parameters like bllod concentration of NAD+, NADH, advanced glycation end products (AGEs), malondialdehyde (MDA), VEGF and VEGFR2 determined? Lastly, yearly fundoscopic examinations were documented to detect the features of DR. These efforts revealed the following findings: 32 among 187 (17.11%) patients who received supplementation with B-vitamins, vitamin C and vitamin E developed very mild microangiopathy; whereas 92 patients among 200 (46%) controlled ones developed mild to moderate non proliferative diabetic retinopathy (NPDR). 13 patients of the study group who didn’t follow up were counted as lost from the observation of the study. The findings lead to this conclusion: Glycolysis and citric acid cycle should run uninterruptedly by supplementation of precursors of oxidized cofactors and antioxidants to prevent biochemical derangements which lead to increased expression of VEGF.
改变生物化学紊乱和VEGF分泌可能预防糖尿病视网膜病变(DR)的研究进展
在包括视网膜在内的胰岛素非依赖性组织中,大量未利用的细胞内葡萄糖会导致以下几种后果:(i)晚期糖基化终产物的形成增加,(ii)多元醇途径的激活,(iii)厌氧糖酵解,(iv)谷氨酸毒性,(v)脂质过氧化和氧化应激,所有这些,最终导致抗原性VEGF和VEGFR2的调控趋同,而VEGF和VEGFR2是DR发展的关键角色。本初步研究的目的是评估一种干预对DR发展的影响:补充b族维生素(B1、B2、B3、B5和B6)、维生素C和维生素E改善与dr发展相关的生化紊乱,该研究确定了400名诊断为2型糖尿病的患者,其中受试者按1:1的比例随机分配,接受口服抗糖尿病药物以及b族维生素、维生素C和维生素E或仅服用抗糖尿病药物,以在2004年12月至2017年12月期间进行这项非混合随机试验。完成了以下初步工作:首先,基线详细眼底检查足以排除视网膜病变的存在。其次,是否测定了血液中NAD+、NADH、晚期糖基化终产物(AGEs)、丙二醛(MDA)、VEGF和VEGFR2等基线生化参数?最后,每年进行一次眼底镜检查,以发现dr的特征。这些努力揭示了以下结果:187例补充b族维生素、维生素C和维生素E的患者中有32例(17.11%)发生了非常轻微的微血管病变;对照组200例中有92例(46%)出现轻至中度非增殖性糖尿病视网膜病变(NPDR)。未随访的研究组患者中有13例被视为从本研究的观察中丢失。研究结果表明:糖酵解和柠檬酸循环应通过补充氧化辅助因子前体和抗氧化剂来不间断地进行,以防止导致VEGF表达增加的生化紊乱。
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