Rachmi Fauziah Rahayu, Fathimah Afifah Zahrah, Tessa Septian Anugrah, Ratih Dewi Yudhani, Yuyun Yueniwati, Amelia Tjandra Irawan, Sulistyani Kusumaningrum, Adam Fauzi, Brian Wasita, Nanang Wiyono, Muthaminah, Tri Agusti Sholikah, Lusi Oka Wardhani, Suyatmi, Kristanto Yuli Yarso, Riza Novierta Pesik, Febby Gunawan Siswanto
BACKGROUND: Diabetes mellitus induces oxidative stress, inflammation, and endothelial dysfunction, accelerating atherosclerosis development marked by elevated high-sensitivity C-reactive protein (hs-CRP) and interleukin-12 (IL-12). Diabetes often causes significant vascular changes, which can be represented by carotid tunica intima thickening and elevated renin level. Metformin, which remains as the standard therapy, has limited vascular effects. Vitamin D and magnesium exhibit vasoprotective and anti-inflammatory properties; however, their combined effects on diabetic vascular injury remain unclear. This study evaluated the effects of vitamin D and magnesium combination on serum hs-CRP, IL-12, renin, and carotid tunica intima thickness in diabetic rats. METHODS: Wistar rats were diabetic-induced by 45 mg/kg streptozotocin and 110 mg/kg nicotinamide. Following the induction, the rats were subsequently assigned to receive no treatment, metformin, or a combination of vitamin D and magnesium. Healthy rats were also included as control. Blood sample was collected after 21 days of treatment. Serum hs-CRP, IL-12, and renin were measured using enzyme-linked immunosorbent assay (ELISA), while the carotid tunica intima thickness was assessed by Doppler ultrasound. RESULTS: Diabetic rats showed significant increases hs-CRP, IL-12, renin level, and intima thickness (p<0.001) compared to control. Both metformin and combination of Vitamin D and magnesium reduced these parameters, with combination of Vitamin D and magnesium showing the greatest improvement. Carotid intima thickness in the combination of Vitamin D and magnesium group was comparable to normal controls, indicating marked vascular protection. CONCLUSION: Vitamin D and magnesium combination provided superior glycemic, anti-inflammatory, and vascular protective effects compared to metformin alone. This adjunctive strategy might have potential in preventing vascular complications in diabetes. Copyright © 2026 The Prodia Education and Research Institute. This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC-BY-NC) License.
Department of Radiology, Faculty of Medicine, Universitas Sebelas Maret, Dr. Moewardi General Hospital, Jl. Kolonel Sutarto No.132, Surakarta, 57126, Indonesia; Department of Pharmacology, Faculty of Medicine, Universitas Sebelas Maret, Jl. Ir. Sutami No. 36, Surakarta, 57126, Indonesia; Department of Radiology, Faculty of Medicine, Universitas Brawijaya, Saiful Anwar General Hospital, Jl. Veteran, Malang, 65145, Indonesia; Doctoral Program in Medical Science, Faculty of Medicine, Universitas Brawijaya, Jl. Veteran, Malang, 65145, Indonesia; Faculty of Medicine, Universitas Muhammadiyah Surakarta, Jl. A. Yani Tromol Pos 1, Sukoharjo, 57169, Indonesia; Department of Pathology Anatomy, Faculty of Medicine, Universitas Sebelas Maret, Jl. Ir. Sutami No. 36, Surakarta, 57126, Indonesia; Department of Anatomy, Faculty of Medicine, Universitas Sebelas Maret, Jl. Ir. Sutami No. 36, Surakarta, 57126, Indonesia; Department of Histology, Faculty of Medicine, Universitas Sebelas Maret, Jl. Ir. Sutami No. 36, Surakarta, 57126, Indonesia; Department of Clinical Pathology, Faculty of Medicine, Universitas Sebelas Maret, Jl. Ir. Sutami No. 36, Surakarta, 57126, Indonesia; Department of Surgery, Faculty of Medicine, Universitas Sebelas Maret, Dr. Moewardi General Hospital, Jl. Kolonel Sutarto No.132, Surakarta, 57126, Indonesia
