<![CDATA[Background: Diabetic Cardiomyopathy (DCM) is defined as structural and functional abnormalities of the myocardium occurring in individuals with Diabetes Mellitus (DM) in the absence of other conventional cardiovascular risk factors. Establishing a reliable early-stage DCM model is essential for mechanistic studies and therapeutic evaluation. This study aimed to characterize an early-stage DCM model in male Sprague–Dawley rats using a High-Fat High-Fructose (HFHF) diet combined with low-dose Streptozotocin (STZ). Methods: Twelve male Sprague–Dawley rats (7–8 weeks, 200–250 g) were randomly assigned to three groups (n=4/group): control, HFHF + STZ 25 mg/kg, and HFHF + STZ 40 mg/kg. Rats received an HFHF diet for 12 weeks, followed by intraperitoneal STZ induction. Fasting blood glucose, lipid profile, cardiac echocardiography, serum N-Terminal pro-B-type Natriuretic Peptide (NT-proBNP), and myocardial histopathology were assessed. Data were analyzed using ANOVA or Kruskal–Wallis as appropriate. Results: Both STZ doses induced persistent hyperglycemia without significant body-weight changes, consistent with a DCM metabolic phenotype. NT-proBNP levels were significantly elevated in both STZ groups compared with controls (p<0.05), indicating early myocardial stress despite preserved systolic and diastolic function on echocardiography. Histopathological evaluation showed increased inflammatory cell infiltration and progressive fibrosis in the HFHF+STZ groups, with a graded pattern across STZ doses. Conclusions: The combination of an HFHF diet and low-dose STZ reproduced an early-stage DCM model characterized by persistent hyperglycemia, elevated NT-proBNP, and early myocardial remodeling while cardiac function remains preserved. This model reflects early DCM and is suitable for mechanistic studies and for testing therapies aimed at preventing progression to advanced myocardial dysfunction.]]>
