Abstract
Cardiovascular mortality is a major cause of death among in type 2 diabetes (T2DM). Endothelial dysfunction (ED) is a well-known important risk factor for the development of diabetes cardiovascular complications. Therefore, the prevention of diabetic macroangiopathies by preserving endothelial function represents a major therapeutic concern for all National Health Systems. Several complex mechanisms support ED in diabetic patients, frequently cross-talking each other: uncoupling of eNOS with impaired endothelium-dependent vascular response, increased ROS production, mitochondrial dysfunction, activation of polyol pathway, generation of advanced glycation end-products (AGEs), activation of protein kinase C (PKC), endothelial inflammation, endothelial apoptosis and senescence, and dysregulation of microRNAs (miRNAs). Metformin is a milestone in T2DM treatment. To date, according to most recent EASD/ADA guidelines, it still represents the first-choice drug in these patients. Intriguingly, several extraglycemic effects of metformin have been recently observed, among which large preclinical and clinical evidence support metformin’s efficacy against ED in T2DM. Metformin seems effective thanks to its favorable action on all the aforementioned pathophysiological ED mechanisms. AMPK pharmacological activation plays a key role, with metformin inhibiting inflammation and improving ED. Therefore, aim of this review is to assess metformin’s beneficial effects on endothelial dysfunction in T2DM, which could preempt development of atherosclerosis.
Highlights
Type 2 diabetes mellitus (T2DM) has been recognized for long a disease of the cardiovascular system, so that, at the beginning of the 1980s, someone has established it as a “cardiovascular disease diagnosed by glycemia”
This anecdotal definition preempted the scientific evidence produced by Haffner in 1998, who demonstrated a similar mortality risk from Coronary Heart Disease (CHD) in a diabetic patient without previous myocardial infarction (MI) as compared to a non-diabetic subject who had suffered from a previous heart ischemic accident [1]
Such a role is consistent with large evidence that increased concentrations of glucose in cultured endothelial cells induce an overproduction of reactive oxygen species (ROS), with the subsequent activation of intracellular signal transduction pathways leading to endothelial dysfunction (ED) [34,35]
Summary
Type 2 diabetes mellitus (T2DM) has been recognized for long a disease of the cardiovascular system, so that, at the beginning of the 1980s, someone has established it as a “cardiovascular disease diagnosed by glycemia”. This anecdotal definition preempted the scientific evidence produced by Haffner in 1998, who demonstrated a similar mortality risk from Coronary Heart Disease (CHD) in a diabetic patient without previous myocardial infarction (MI) as compared to a non-diabetic subject who had suffered from a previous heart ischemic accident [1]. We address the impact of metformin’s administration on macrovascular complications of diabetes. We analyze metformin’s beneficial effects on that distinctive pathophysiological condition named endothelial dysfunction (ED), which preempts the early development of atherosclerosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
