Alteration in haemodynamics and pathological changes in the cardiovascular system during the development of Type 2 diabetes mellitus in OLETF rats

Aims/hypothesis The process of cardiovascular complications in Type 2 diabetes mellitus (DM) is unclear. We investigated pathophysiological changes of the heart and vessels in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat Type 2 DM model during a long time period.Methods Echocardiography was carried out at 22 and 62 weeks of age of OLETF (n=10, each) and age-matched Long-Evans Tokushima Otsuka (LETO) rats (n=10, each) as a reference. Haemodynamic measurements and histological examinations of the heart and the coronary and aortic vascular walls were done.Results The left ventricular (LV) maximal -dP/dt was reduced in OLETF rats at 62 weeks (–1085±35 mmHg/s) less than that at 22 weeks (–1892±396 mmHg/sec,p<0.05) and in LETO rats at 62 weeks (–1306±200 mmHg/sec,p<0.05). Wall thickening of intramyocardial coronary arteries, capillary tortuosity and thickening of basement membrane were evident in OLETF rats at 62 weeks. Intimal and medial wall thickening of the aorta were prominent in OLETF rats at 62 weeks (15±2.2 and 90±6.6 µm, in LETO rats at 62 weeks, 2±0.4 and 65±5.2 µm,p <0.05, and in OLETF rats at 22 weeks, 7±4.6 and 71±6.0 µm, p<0.05, respectively).Conclusions/interpretation In the Type 2 DM model, angiopathy, especially in coronary arteries including small vessels, as well as a LV relaxation abnormality, are induced in a late stage of DM. These are considered to be important complications in Type 2 DM.Abbreviations OLETF Otsuka Long-Evans Tokushima Fatty - DM diabetes mellitus - LETO Long-Evans Tokushima Otsuka - STZ streptozotocin - 2-DE two-dimensional echocardiography - LVDd left ventricular end-diastolic diameter - LVDs left ventricular end-systolic diameter - IVST diastolic intraventricular septal wall thickness - LVPWT left ventricular posterior wall thickness - LVEF left ventricular ejection fraction - LV left ventricle - dP/dt first derivative of LV pressure