Cardiovascular sexual dimorphism in a diet-induced type 2 diabetes rodent model, the Nile rat (Arvicanthis niloticus)

The Nile rat (Arvicanthis niloticus) is an emerging laboratory model of type 2 diabetes. When fed standard rodent chow, the majority of males progress from hyperinsulinemia by 2 months to hyperglycemia by 6 months, while most females remain at the hyperinsulinemia-only stage (prediabetic) from 2 months onward. Since diabetic cardiomyopathy is the major cause of type-2 diabetes mellitus (T2DM)-related mortality, we examined whether sexual dimorphism might entail cardiac functional changes. Our ultimate goal was to isolate the effect of diet as a modifiable lifestyle factor. Nile rats were fed either standard rodent chow (Chow group) or a high-fiber diet previously established to prevent type 2 diabetes (Fiber group). Cardiac function was determined with echocardiography at 12 months of age. To isolate the effect of diet alone, only the small subset of animals resistant to both hyperinsulinemia and hyperglycemia were included in this study. In males, Chow (compared to Fiber) was associated with elevated heart rate and mitral E/A velocity ratio, and with lower e'-wave velocity, isovolumetric relaxation time, and ejection time. Of note, these clinically atypical types of diastolic dysfunction occurred independently of body weight. In contrast, females did not exhibit changes in cardiovascular function between diets. The higher prevalence of T2DM in males correlates with their susceptibility to develop subtle diastolic cardiac dysfunction when fed a Western style diet (throughout most of their lifespan) despite no systemic evidence of metabolic syndrome, let alone T2DM.