Effect of hyper-caloric intake on hemodynamic functions and cardiac autonomic control : potential modulation by anti-diabetic drugs

Abstract

Diabetes mellitus remains a public health challenge with considerable disease and economic consequences. Mortality and morbidity due to diabetes are related to the poor cardiovascular outcomes. A significant body of research describes the detrimental effect of hyperglycemia on vascular function and the importance of tight blood glucose control in delaying progression of diabetes micro-vascular complications. It is generally agreed that the impact of glycemic control on cardiovascular complications is influenced by the temporal framework in which an acceptable blood glucose level has been achieved, in what became known as the “Legacy effect” or the “Cardiovascular metabolic memory”. On the other hand, recent clinical evidence paints a different picture, whereby treatment with certain anti-hyperglycemic drugs on top of the standard-of-care for diabetes and cardiovascular disease leads to cardiovascular risk reduction, in a manner that is not necessarily tightly linked to their effect on glycemic control.In parallel, recent studies reported cardiovascular abnormalities in animal models of high caloric intake before the development of frank hyperglycemia. We recently developed a rat model of hyper-caloric feeding that was shown to develop vascular dysfunction without changes in blood pressure, serum glucose, or insulin levels. As such, we propose to use this model to characterize early hemodynamic changes occurring in the context of development of diabetes, study the underlying pathological mechanism, track the evolution of these disorders, and examine the effect of early treatment with some of the anti-hyperglycemic drugs with presumed cardiovascular benefit. Control and high calorie fed rat groups will be run side-by-side for 12 weeks. Body weight and caloric intake will be assessed regularly. Non-invasive blood pressure measurement and hemodynamic parameter assessment by echocardiography will be carried out at four-week intervals. Sub-groups of the high calorie fed rats will be given