Abstract
Background: Diabetes mellitus (DM) is a major risk factor for cardiovascular diseases.
The progression of myocardial abnormalities due to DM occurs slowly but is progressive and
asymptomatic. Sodium-glucose transport protein 2 inhibitors (SGLT-2i) and Vitamin D have
potential cardioprotective properties that inhibit cardiomyocyte fibrosis and hypertrophy, which
are early structural changes that occur in the heart of DM patients.
Aim: The study aimed to determine the potential protective effects of SGLT-2i and Vitamin D
administration on cardiac hypertrophy and fibrosis in Type 2 diabetic rats.
Methods: This is an experimental study with a post-test-only control group design. Thirty-two
male Wistar rats were given a high-fat/high-glucose (HF/HG) diet. After 3 weeks, rats were given
an injection of streptozotocin (STZ 35 mg/kg) to induce pancreatic damage. The diabetic rats
were then divided into four groups (n = 8 per group): untreated diabetic group (HF/HG/STZ),
the diabetic group treated with empagliflozin (EMPA) 10 mg/kg body weight (BW) (HF/HG/
STZ+EMPA), the diabetic group treated with Vitamin D 225 IU/day (HF/HG/STZ+VitD), and the
diabetic group treated with a combination of EMPA 10 mg/kg BW and Vitamin D 225 IU/day (HF/
HG/STZ+EMPA+VitD). Treatments were given by oral gavage for 8 weeks. Left ventricular biopsy
was performed at week 13 to examine collagen deposition, the cardiomyocyte cross-sectional area
(CSA), and the mRNA expression of β-myosin heavy chain (β-MHC) and transforming growth
factor-β (TGF-β). All the obtained data were analyzed statistically.
Results: The administration of EMPA, Vitamin D, and combination therapy of EMPA and Vitamin
D reduced the mRNA expression of β-MHC and TGF-β in diabetic rats compared to the untreated
diabetic group. The administration of EMPA, Vitamin D, and combination therapy also resulted in
a decrease in both the cardiomyocyte CSA and collagen deposition. Compared to monotherapy, combination therapy led to significantly better parameter reduction.
Conclusion: Administration of EMPA, Vitamin D, and combination therapy improved cardiac
hypertrophy and fibrosis in type 2 diabetic rats.
Relevance for Patients: The combination of Vitamin D and SGLT-2i may be proposed as a
cardioprotective strategy and preventive measure to reduce the incidence of cardiovascular disease
in patients with Type 2 DM.
DOI: http://doi.org/10.36922/jctr.24.00010
Author affiliation
1Department of Cardiology and Vascular Medicine, Faculty of Medicine Udayana University/Prof. I.G.N.G Ngoerah General Hospital, Bali,
Indonesia
2Department of Histology, Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia
*Corresponding author:
Nyoman Ririn Chandrika Sari
Department of Cardiology and Vascular
Medicine, Faculty of Medicine, Udayana
University, Denpasar, Bali, Indonesia
Email: ririnchandrika@gmail.com
Downloads:
Full-text PDF
