Earlier onset of diabesity‐Induced adverse cardiac remodeling in female compared to male mice

Objective Emerging evidence suggests female type 2 diabetes (T2DM) patients may fare worse than males with respect to cardiovascular complications. Hence the impact of sex on relative progression of left ventricular (LV) remodeling in obese db/db mice was characterized. Methods The changes in parameters of LV hypertrophy (heart weight, pro‐hypertrophic gene expression, cardiomyocyte size) and fibrosis (LV collagen deposition and oxidative stress), in parallel with body weight and blood glucose and lipid profiles, in male and female db/db T2DM mice, at 10, 14, and 18 weeks of age, were determined. Results Diabesity‐induced cardiac remodeling was at least comparable in female (compared to male) mice. Females exhibited enhanced systemic oxidative stress and nonesterified fatty acid levels. Progression of LV pro‐hypertrophic (β‐myosin heavy chain, B‐type natriuretic peptide) and pro‐oxidant gene expression (NADPH oxidase subunit Nox2, plasminogen activator inhibitor‐1 PAI‐I) was, however, exaggerated in females when expressed relative to 10‐week‐old db/db mice. Increased cardiomyocyte width was also evident earlier in db/db females than males. No other gender differences were observed. Conclusions Progressive, age‐dependent development of cardiac remodeling in db/db mice parallels impairments in glucose handling and oxidative stress. Certain aspects of the T2DM‐induced LV remodeling response may have an earlier and/or exaggerated onset in diabetic females.