Title:Diabetes and Vascular Disease: Is It All About Glycemia?
Volume: 25
Issue: 29
Author(s): Alessandra Vecchié, Fabrizio Montecucco, Federico Carbone, Franco Dallegri and Aldo Bonaventura*
Affiliation:
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa,Italy
Keywords:
Diabetes, atherosclerosis, endothelial dysfunction, NETs, platelets, oxidative stress.
Abstract:
Background: Diabetes is increasing over time, mainly driven by obesity, aging, and urbanization.
Classical macro- and microvascular complications represent the final result of a complex interplay involving
atherosclerosis at all stages.
Methods: In this review, we aim at focusing on current updates in the pathophysiology of vascular disease in
diabetes and discussing how new therapies might influence the management of these patients at high cardiovascular
risk. Diabetes shows accelerated atherosclerosis with a larger inflammatory cell infiltrate, thus favoring the
development of heart failure. ‘Diabetic cardiomyopathy’ perfectly describes a specific ischemia- and hypertension-
independent entity due to diabetes-related metabolic alterations on myocardial function. Moreover, platelets
from subjects with diabetes display a typical hyperreactivity explaining the stronger adhesion, activation, and
aggregation. Additionally, diabetes provokes an exaggerated stimulation of the endothelium, with an increased
release of reactive oxygen species and a reduced release of nitric oxide, both key elements of the endothelial
dysfunction. Also, the coagulation cascade and leukocytes activate contributing to this pro-thrombotic environment.
Neutrophils have been recently recognized to play a pivotal role by releasing neutrophil extracellular traps.
Finally, microparticles from platelets, neutrophils or monocytes are detrimental effectors on the vessel wall and
are involved both in vascular dysfunction and in thrombotic complications.
Conclusion: In light of these findings, the therapeutic management of diabetes needs to be mostly focused on
limiting the progression of complications by targeting precise pathophysiological mechanisms rather than the
mere glycemic control, which failed to markedly reduce the risk for macrovascular complications and mortality.
