Glycaemic Control and Vascular Complications in Diabetes Mellitus Type 2
Diabetes mellitus is constantly increasing worldwide. Vascular complications are the most common in the setting of long-standing disease, claiming the greatest burden in terms of morbidity and mortality. Glucotoxicity is involved in vascular damage throug
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Glycaemic Control and Vascular Complications in Diabetes Mellitus Type 2 Francesco Maranta, Lorenzo Cianfanelli, and Domenico Cianflone Abstract
Diabetes mellitus is constantly increasing worldwide. Vascular complications are the most common in the setting of long-standing disease, claiming the greatest burden in terms of morbidity and mortality. Glucotoxicity is involved in vascular damage through different metabolic pathways, such as production of advanced glycation end-products, activation of protein kinase C, polyol pathway activation and production of reactive oxygen species. Vascular complications can be classified according to the calibre of the vessels involved as microvascular (such as diabetic retinopathy, nephropathy and neuropathy) or macrovascular (such as cerebrovascular, coronary and peripheral artery disease). Previous studies showed that the severity of vascular complications depends on duration and degree of hyperglycaemia and, as consequence, early trials were designed to prove that intensive glucose control could reduce the number of vascular events. Unfortunately, results were F. Maranta (*) Cardiac Rehabilitation Unit, San Raffaele Scientific Institute, Milan, Italy e-mail: [email protected] L. Cianfanelli and D. Cianflone Vita-Salute San Raffaele University and San Raffaele Scientific Institute, Milan, Italy
not as satisfactory as expected. Trials showed good results in reducing incidence of microvascular complications but coronary heart diseases, strokes and peripheral artery diseases were not affected despite optimal glycemia control. In 2008, after the demonstration that rosiglitazone increases cardiovascular risk, FDA demanded stricter rules for marketing glucose-lowering drugs, marking the beginning of cardiovascular outcome trials, whose function is to demonstrate the cardiovascular safety of anti-diabetic drugs. The introduction of new molecules led to a change in diabetes treatment, as some new glucose-lowering drugs showed not only to be safe but also to ensure cardiovascular benefit to diabetic patients. Empaglifozin, a sodium-glucose cotransporter 2 inhibitor, was the first molecule to show impressing results, followed on by glucagon-like peptide 1 receptor agonists, such as liraglutide. A combination of antiatherogenic effects and hemodynamic improvements are likely explanations of the observed reduction in cardiovascular events and mortality. These evidences have opened a completely new era in the field of glucoselowering drugs and of diabetes treatment in particular with respect to vascular complications.
F. Maranta et al.
Keywords
Atherosclerosis · Cardiovascular complications · CVOT · Diabetes · Glycaemic control · Nephropathy · Neuropathy · Peripheral artery disease
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Introduction
During last years, prevalence of diabetes mellitus (DM) has risen considerably both in developed and developing countries. The high number of patients involved and the
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