Role of magnesium and thiamine deficiency-mediated carbonyl stress in diabetic neuropathy and kidney disease

糖尿病神经病变（DN）和糖尿病肾病（DKD）是30-40%的1型或2型糖尿病患者中高度流行的糖尿病微血管并发症。在过去的二十年中，积累了将甲基甘氨酸介导的羰基应激与糖尿病微血管并发症联系起来的证据。作为戊糖磷酸途径中的主要硫胺素靶标的转酮醇酶、丙酮酸脱氢酶和α-酮戊二酸脱氢酶需要硫胺素和镁来实现催化活性。根据文献和我们的发现，硫胺素缺乏、低镁血症和由此产生的羰基应激有助于DN和DKD的发展。在拟议的研究中，我们的目的是研究联合补充镁和硫胺素作为一种新的治疗方法，以保护免受甲基甘氨酸介导的羰基应激，从而预防DN和DKD的影响。本实验研究的结果可能对评估硫胺素或其衍生物在DN和DKD中的潜在疾病改善作用的临床试验的设计和结果产生重大影响。

Diabetic neuropathy (DN) and diabetic kidney disease (DKD) are highly prevalent microvascular complications of diabetes encountered in 30-40% of people with type 1 or type 2 diabetes. Over the last two decades, evidence linking methylglyoxal-mediated carbonyl stress to diabetic microvascular complications has accumulated. Transketolase, as the main thiamine target in the pentose phosphate pathway, pyruvate dehydrogenase, and α-ketoglutarate dehydrogenase require both thiamine and magnesium for catalytic activity. Based on the literature and our findings thiamine deficiency, hypomagnesemia and the resulting carbonyl stress contribute to the development of DN and DKD. In the proposed study, we aim to investigate the effects of combined magnesium and thiamine supplementation as a new therapeutic approach to protect from methylglyoxal-mediated carbonyl stress and thereby prevent from DN and DKD. The results of this experimental study could have a major impact on the design and outcome of clinical trials assessing the potential disease modifying effects of thiamine or its derivatives in DN and DKD.