Introduction Type 2 diabetes results in metabolic dysregulation, which, in turn leads to impaired cardiac function. While diabetes is more prevalent in men, women with diabetes face a higher risk of cardiovascular disease. Despite this, little is known about sex differences in metabolic regulation and how this may affect cardiac function in diabetes. Methods Diabetes was induced in male and female Wistar rats (n=6 per group) using high-fat diet combined with a low dose of streptozotocin (27 mg/kg). Cardiac function was assessed using echocardiography. Blood and tissue were collected and analysed to assess metabolic changes. Mechanisms underlying the sex-specific differences were further investigated through pathway enrichment analysis from RNA sequencing. Results Diabetic males exhibited a worse metabolic profile, with more pronounced hyperglycaemia than seen in diabetic females (control males 12.34 ± 0.41 vs diabetic males 14.53 ± 0.78 mmol/L; control females: 11.05 ± 0.21 vs diabetic females 11.96 ± 0.29 mmol/L). A similar trend was seen when assessing blood lipid concentrations, as hyperlipidaemia was only seen in male diabetic animals and not females (figure 1a). The extent of hepatic triglyceride storage, indicative of fatty liver disease, was more prominent in diabetic males (increased by 39%) than in diabetic females (increased by 28%), compared with their respective chow fed controls. While cardiac fatty acid β-oxidation protein expression was elevated in both diabetic males and females compared to their respective controls, the increase was more pronounced in males (figure 1b). Despite a relatively protected metabolic profile, only diabetic females exhibited early signs of diastolic dysfunction, with reduced left ventricular end diastolic diameter, E/A ratio and stroke volume, which were not observed in diabetic males (figure 2). Conclusions Our findings highlight sex-specific differences in metabolic and cardiac dysfunction in this model of type 2 diabetes. While males experienced greater metabolic impairment, females presented with worsened cardiac function despite a comparatively favourable metabolic profile.
Josh et al. (Wed,) studied this question.