Energy-Dense High-Fat/High-Sucrose Diet to Induce Type 2 Diabetes Mellitus in BALB/c Mice Without Genetic Modifications and Chemical Agents

Type 2 diabetes mellitus (T2DM) is a highly prevalent disease characterized by chronic hyperglycemia, commonly associated with intake of a high-calorie diet (HCD). Although numerous T2DM murine models have been developed using C57BL/6 mice, BALB/c mice typically fail to develop the disease under the same conditions. We hypothesized that diets optimized for C57BL/6 mice may be insufficient to induce T2DM in BALB/c mice. Female BALB/c and C57BL/6 mice (n = 48 each) were fed either a specific high-calorie diet (HCD) or a standard diet (SD) for ten weeks. BALB/c mice fed a specific HCD exhibited developed persistent hyperglycemia (112.6 mg/dL ± 3.4) from week 1 through week 10, while SD-fed controls maintained normal glucose levels (84.2 mg/dL ± 2.8). HCD-fed BALB/c mice showed elevated serum insulin (39.09 pg/dL ± 25.94), triglycerides (290.8 mg/dL ± 139.5), HOMA index (7.68 ± 1.49) and high post-challenge glucose along with visceral adiposity, hepatic steatosis, and pancreatic alterations. SD-fed BALB/c mice showed no such changes. Similar findings were observed in C57BL/6 mice, used as a positive disease-control group. This model demonstrates that a properly formulated HCD can induce T2DM in BALB/c mice, enabling the study of genes and molecules associated with diabetes susceptibility without requiring genetic or chemical manipulation.