Vitamin D and Magnesium Combination Lowers High-Sensitivity C-Reactive Protein, Interleukin-12, Renin, and Carotid Vessel in Diabetic Rats

Rahayu, Rachmi Fauziah
Zahrah, Fathimah Afifah
Anugrah, Tessa Septian
Yudhani, Ratih Dewi
Yueniwati, Yuyun
Irawan, Amelia Tjandra
Kusumaningrum, Sulistyani
Fauzi, Adam
Wasita, Brian
Wiyono, Nanang
Muthaminah, Muthaminah
Sholikah, Tri Agusti
Wardhani, Lusi Oka
Suyatmi, Suyatmi
Yarso, Kristanto Yuli
Pesik, Riza Novierta
Siswanto, Febby Gunawan

The Indonesian Biomedical Journal
Vol 18, No 2 (2026)

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.KEYWORDS: diabetes mellitus, oxidative stress, endothelial dysfunction, hs-CRP, IL-12, atherosclerosis