Kateel Ramya, Kashyap Namita N, Reddy Shivakumar K, Shetty Sahana, Kumari Meena K, Ullal Sheetal D, Holla Sadhana N, Aroor Annayya, Hill Michael A, Belle Vijetha Shenoy, Prabhu Krishnananda, Joshi Manjunath B, Upadhya Dinesh
Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
Centre for Molecular Neurosciences, Department of Anatomy, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
Clin Nutr. 2025 Jul;50:183-197. doi: 10.1016/j.clnu.2025.05.004. Epub 2025 May 17.
Aged type 2 diabetes mellitus (T2DM) patients are linked with lower serum levels of total antioxidant activity, magnesium and zinc, particularly under uncontrolled hyperglycemia. Uncontrolled oxidative stress is an established contributor to diabetic complications. Magnesium is a cofactor for ∼600 enzymes, while zinc is a part of ∼3000 human proteins, essential for intermediary metabolism. A multi-targeted approach combining β-carotene, Magnesium and Zinc (BMZ) with metformin or vitamin E, Magnesium and Zinc (EMZ) with metformin for daily use in aged rats with T2DM identified astonishing findings compared to metformin monotherapy. Over three months, compared to metformin monotherapy, BMZ with metformin provided excellent glycemic control, outstanding protection against potential neuropathy and sensorimotor coordination, maintained robust retinal integrity and provided significant control for diabetic nephropathy. Mechanistically, the significant improvement in BMZ with metformin in controlling retinopathy, nephropathy, and neuropathy are directly linked to (1) Increased glycemic control (antihyperglycemic effect), (2) increased insulin sensitivity as evidenced by reduced HOMA-IR levels, (3) reduced oxidative stress (4) increased antioxidant activity through increased glutathione levels and increased GSH/GSSG ratio, and (5) improved regulation of carbohydrate and lipid metabolism as evidenced by metabolomic data. This study provides robust and direct evidence to support the use of affordable, proven antioxidant and mineral combinations with metformin to reduce diabetes-related complications in aging.
老年2型糖尿病（T2DM）患者血清中的总抗氧化活性、镁和锌水平较低，尤其是在血糖控制不佳的情况下。不受控制的氧化应激是导致糖尿病并发症的一个既定因素。镁是约600种酶的辅助因子，而锌是约3000种人类蛋白质的组成部分，对中间代谢至关重要。将β-胡萝卜素、镁和锌（BMZ）与二甲双胍联合使用，或维生素E、镁和锌（EMZ）与二甲双胍联合用于老年T2DM大鼠的日常治疗，与二甲双胍单药治疗相比，发现了惊人的结果。在三个月的时间里，与二甲双胍单药治疗相比，BMZ联合二甲双胍能提供出色的血糖控制，对潜在神经病变和感觉运动协调有出色的保护作用，维持强大的视网膜完整性，并对糖尿病肾病有显著的控制效果。从机制上讲，BMZ联合二甲双胍在控制视网膜病变、肾病和神经病变方面的显著改善直接与以下因素有关：（1）血糖控制改善（抗高血糖作用），（2）胰岛素敏感性增加，这可通过降低HOMA-IR水平得到证明，（3）氧化应激降低，（4）通过增加谷胱甘肽水平和提高GSH/GSSG比值增加抗氧化活性，以及（5）碳水化合物和脂质代谢调节改善，这可通过代谢组学数据得到证明。这项研究提供了有力而直接的证据，支持使用价格合理、经证实的抗氧化剂和矿物质组合与二甲双胍联合使用，以减少衰老过程中与糖尿病相关的并发症。
