Endocrine Abstracts

Background: Cardiovascular events are the major cause of mortality among patients with type 2 diabetes mellitus (DM2). Menopause in women additionally increases cardiovascular risk. Despite myocardial infarction (MI) treatment approach in diabetic patients is not specific, some glucose-lowering drugs could have cardioprotective properties. In general, most glucagon-like peptide-1 receptor agonists (GLP-1Ra) and sodium-glucose co-transporter-2 inhibitors (SGLT-2i) have cardiovascular advantages. Particularly, liraglutide (LIRA), semaglutide, empagliflozin, canagliflozin (CANA), dapagliflozin decrease MI incidence. However, SGLT-2i and GLP-1Ra influence on MI manifestations, damage volume and severity in patients with DM2 remains the subject for further investigation. Moreover the cardiotropic properties of these drugs in menopause diabetic subjects undergoing MI is even less studied.

Aim: To evaluate the effect of CANA in comparison with LIRA on myocardial damage area in menopause type 2 diabetic rats in experimental MI.

Materials and methods: Female Wistar rats were subjected to bilateral ovariectomy on order to induce menopause. DM2 was modelled by high-fat diet and streptozotocin 60 mg/kg +nicotinamide 230 mg/kg injection. Rats in control group were fed with standard chow. The following groups were formed: “DM+M” (ovariectomized (menopause) rats with DM2, n=5), “DM+M+CANA” (ovariectomized rats with DM2 treated with CANA 25 mg/kg for 8 weeks, n=5), “DM+M+LIRA” (ovariectomized rats with DM2 treated with LIRA 0,06 mg/kg for 8 weeks, n=4), “CRL” (females without any procedures, n=5). After 16 weeks of treatment transient global myocardial 30-min ischemia of isolated heart was modelled in all rats. Myocardium necrosis area was evaluated after 90 min of reperfusion.

Results: Necrosis area was significantly larger in “DM+M” group (42.00 (34.00; 70.00) % of total heart area) in comparison to “CRL” group (33.00 (22.60; 40.00) %, P=0.003). Both LIRA and CANA administration led to decrease of myocardial damage area (31.67 (15.50; 46.00) % and 31.75 (24.00; 59.00) %, respectively) in comparison with “DM+M” (42.00 (34.00; 70.00) %) group (significantly for LIRA, P=0.009 and statistical tendency for CANA, P=0.07). Importantly, there was no significant difference in myocardial damage area between “DM+M+CANA” and “DM+M+LIRA” groups, P=0.2. Glucose control was similarly satisfactory in both treatment groups.

Conclusions: Both LIRA and CANA similarly decrease heart necrosis area in menopause diabetic rats with myocardial infarction.