Development and Validation of a Novel Experimental Model for Quick Induction of Prediabetes and Studying Cardiometabolic Effects

Abstract

Objective: Prediabetes is a chronic metabolic disorder increasingly recognized as a major contributor to morbidity
and mortality worldwide. Its gradual progression poses challenges for experimental modeling. This study aimed
to establish and characterize a novel approach for inducing early and sustained prediabetes in rats. Method:
Adult male rats were subjected to a high-fat diet, followed by a liquid diet composed of vanaspati ghee and
coconut oil (3:1 ratio), along with 25% dextrose in drinking water for eight weeks. The onset of prediabetes
was verified through biochemical assessments, including fasting blood glucose (FBG), HbA1c, insulin levels,
HOMA-IR, and HOMA-β indices, complemented by histopathological and transmission electron microscopy
analyses. Results and Conclusion: Biochemical evaluation confirmed prediabetes, as evidenced by significant
elevations in FBG and HbA1c (p < 0.05). Additionally, increased insulin resistance (HOMA-IR) and impaired
β-cell function (HOMA-β) were observed. Histopathological examination of the pancreas revealed structural
alterations, while ultrastructural analysis demonstrated compromised insulin secretory granules, further validating
β-cell dysfunction. This experimental model successfully achieved rapid and sustained progression of prediabetes,
replicating the dual features of insulin resistance and early β-cell impairment characteristic of human disease.
In conclusion, this study introduces a reliable and efficient method for inducing prediabetes in rodents. The
model closely reflects the pathophysiological mechanisms underlying human prediabetes, offering a valuable
platform for investigating disease progression and potential therapeutic interventions. Significance: Using this
new approach of a novel animal model for prediabetes, we could expedite the development of prediabetes and
demonstrate the role of insulin resistance and beta cell dysfunction in prediabetes.