Title:Endothelium as a Therapeutic Target in Diabetes Mellitus: From Basic Mechanisms to Clinical Practice
Volume: 27
Issue: 7
Author(s): Anastasios Tentolouris, Ioanna Eleftheriadou, Evangelia Tzeravini, Dimitrios Tsilingiris, Stavroula A. Paschou, Gerasimos Siasos and Nikolaos Tentolouris*
Affiliation:
- Diabetes Center, 1st Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens,Greece
Keywords:
Endothelium, diabetes mellitus, diabetic complications, antidiabetic medication, lipid-lowering medication,
antiplatelet medication, antihypertensive medication.
Abstract: Endothelium plays an essential role in human homeostasis by regulating arterial
blood pressure, distributing nutrients and hormones as well as providing a smooth surface
that modulates coagulation, fibrinolysis and inflammation. Endothelial dysfunction is present
in Diabetes Mellitus (DM) and contributes to the development and progression of
macrovascular disease, while it is also associated with most of the microvascular complications
such as diabetic retinopathy, nephropathy and neuropathy. Hyperglycemia, insulin resistance,
hyperinsulinemia and dyslipidemia are the main factors involved in the pathogenesis
of endothelial dysfunction. Regarding antidiabetic medication, metformin, gliclazide,
pioglitazone, exenatide and dapagliflozin exert a beneficial effect on Endothelial Function
(EF); glimepiride and glibenclamide, dipeptidyl peptidase-4 inhibitors and liraglutide have a
neutral effect, while studies examining the effect of insulin analogues, empagliflozin and
canagliflozin on EF are limited. In terms of lipid-lowering medication, statins improve EF in
subjects with DM, while data from short-term trials suggest that fenofibrate improves EF;
ezetimibe also improves EF but further studies are required in people with DM. The effect
of acetylsalicylic acid on EF is dose-dependent and lower doses improve EF while higher
ones do not. Clopidogrel improves EF, but more studies in subjects with DM are required.
Furthermore, angiotensin- converting-enzyme inhibitors /angiotensin II receptor blockers
improve EF. Phosphodiesterase type 5 inhibitors improve EF locally in the corpus cavernosum.
Finally, cilostazol exerts favorable effect on EF, nevertheless, more data in people with
DM are required.
