Diabetes mellitus (DBT) constitutes an epidemic worldwide, since it affects almost 100 million people.Most correspond to DBT type 2 (90%);While only 10% presents DBT type 1. DBT is an independent risk factor of coronary heart disease, mainly due to atherosclerosis.The absolute risk of cardiovascular disease is at least twice in people with DBT than in those without this disease.

The intensive treatment of risk factors led to a 50% reduction in the rate of cardiovascular events in patients with DBT.Metabolic syndrome is also a significant predictor of cardiovascular disease.In various studies and reviews, the deleterious effects of the DBT on the vascular endothelium and equated the DBT with the underlying coronary arterial disease in the global cardiovascular risk were evaluated.In this study, the association of the DBT was reviewed with vascular disease and diagnostic and therapeutic challenges.

Diabetic cardiac autonomic neuropathy

Diabetic neuropathy is a serious complication of the DBT, which leads to the alteration of cardiovascular autonomic control, with important morbidity and mortality.The etiology seems to relate to the increase in oxidative stress in the DBT, with the increase in lipid peroxidation.The anti -inflammatory role of statins in the treatment of diabetic polyneuropathy was demonstrated.

Diabetic cardiac autonomic neuropathy (NACD) is defined as the alteration in cardiovascular autonomic control in people with DBT, after excluding other causes.The Nacd can cause alterations in the heart rate at rest and with the activity, which leads to the intolerance to the exercise, orthostatic changes in blood pressure and heart rate, prolongation of the QT interval, changes in diurnal and nocturnal blood pressure, ischemiaSilent and diabetic myocardiopathy.

It is a difficult pathology to diagnose and treat and requires a multifactorial approach.The Nacd can be clinical and subclinical.Parasympathetic denervation is usually the first alteration, while in subsequent stages, there is progression to sympathetic denervation, with postural orthostatic hypotension.Orthostatic hypotension is a manifestation of severe Nacd due to progressive autonomic dysfunction that influences the sympathetic tone.

The ineffective response of heart rate and inadequate peripheral vasoconstriction, which are a consequence of the alterations in the sensitivity of the baroreceptors and the release of norepinephrine, cause postural changes in cardiac spending, dizziness or orthostatic syncope.The alteration in the variability of the heart rate is one of the first signs found in the subclinical phase of the NACD.

The decrease in the variability of beats during deep inspiration with inhibition of vagal tone seems to be a reflection of anomalies in autonomic (parasympathetic) heart activity in people with DBT, which manifests itself before other clinical symptoms of diabetic neuropathy.The fixed heart rate that is not modified with sleep, exercise or stress was considered as a sign of cardiac denervation.The level of hyperglycemia and the duration of the DBT were associated with the alterations in the variability of the heart rate, especially in the first five to ten years of the disease.The Nacd can cause diabetic cardiomyopathy due to changes in vagal sympathetic imbalance, with the left ventricular hypertrophy and subsequent remodeling.At the cellular level, parasympathetic denervation increases the release of catecholamines, which causes mitochondrial decoupling and the change in energy generation of glucose to acidsFree fatty.

The increase in oxygen demand and its consumption during heart work leads to hypertrophy and remodeling.Diastolic dysfunction is often the only alteration found in the echocardiogram in initial stages of diabetic myocardiomy.Nuclear magnetic resonance is able to detect the initial stages of the NACD.The Nacd causes alterations in the perception of pain due to sensory denervation, which can explain the lower angina rates during exercise tests in patients with DBT compared to those without the disease.Silent coronary heart disease was described in up to 23% of patients with low -risk DBT and up to 60% of high -risk.The silent myocardium infarction is also more frequent in the DBT and is associated with worse prognosis.

Erectile dysfunction is a manifestation of significant vascular disease in people with DBT, which merits the investigation of coronary heart disease.

Respiratory disorders during sleep were associated with an increase in cardiovascular morbidity and share many of the NCAD characteristics.The greatest severity of the obstructive sleep apnea was related to an increase in prevalence and worse control of metabolic syndrome and type 2 DBT.

The DBT was also associated with an increased risk of sudden cardiac death due mainly to silent ischemia and autonomic dysfunction, which produce arrhythmogenic alterations in the repolarization and variability of heart rate.Other risk factors for sudden death in DBT are diabetic myocardiopathy, alteration in pulmonary response to hypoxia and hypercapnia, hypoglycemia and hypercoagulability.

diabetes, inflammation and oxidative stress

DBT is the main cause of expression of inflammatory markers that produce direct damage to the cardiovascular system and enhance the negative effects on other cardiovascular risk factors.Hyperglycemia in DBT produces an increase in intracellular glucose that triggers various inflammatory reactions that produce free radicals derived from highly toxic oxygen.The production of vascular superoxides causes endothelial dysfunction in the DBT.

The generation of superoxides activates other inflammatory and oxidative pathways, with generation of more superoxides.Superoxides inactivate the relaxation factor derived from endothelium and nitric oxide, with highly toxic reactants such as peroxyinitrite, which produces depletion of nitric oxide and endothelial dysfunction along with the generation of free radicals derived from oxygen that produce more damage throughlipid peroxidation.

Antioxidants restored vasodilation dependent on endothelium altered by hyperglycemia and protected against the toxic effects of reactive oxygen species.Hyperglycemia alters the signaling of physiological nitric oxide in the DBT, with decrease in the endothelial response to nitric oxide and increase in endothelial dysfunction and propagation of the toxicity of reactive oxygen species.Endothelial dysfunction affects other non -cardiac tissues and consequently diabetic nephropathy, neuropathy and retinopathy occurs.Oxidative stress also increases inflammatory markers in gestational diabetes and in the evolution of Alzheimer's disease.Diabetic myocardiopathy was attributed to the apopptotic effect of oxidative stress by activating proinflammatory ways, with cell death and myocardial dysfunction.The Nacd also related to the increase in oxidative stress.

Diabetes y Atherosclerosis

DBT is the main risk factor for the appearance of diseaseAtherosclerotic cardiovascular, which is influenced by oxidative stress.The formation of final products of advanced glycosylation was linked to the appearance of diabetic atherogenic dyslipidemia.Glucosylation of high density lipoproteins (HDL) in DBT tends to reduce its protective effect and worsen atherosclerosis.Adipokines can directly mediate atherosclerosis by influencing the function of endothelial cells, blood pressure cells and macrophages on vascular walls.

Adiponectin that tends to be vasculoprotective against diabetic atherosclerosis, is diminished in type 2 DBT, obesity or metabolic syndrome.Existing studies indicate that the improvement in glycemic control in DBT type 2 did not prove the rate of macrovascular events;But it is essential for the control of inflammatory and oxidative stress and its impact on atherosclerosis and the decrease in microvascular disease.The lipid profile in diabetic atherogenic dyslipidemia demonstrates a predominance of low density lipoproteins (LDL), diminished and generally dysfunctional HDL and increased triglycerides.It is crucial to evaluate and control the risk factors of diabetic vascular atherosclerosis, non -traditional inflammation risk factors and the oxidation of LDL that tend to be more pronounced in the population with DBT.

Diabetic vasculopathy and current therapy

The therapeutic approach in hyperglycemia is only one of the components of DBT treatment.Traditional risk factors for heart disease and stroke are enhanced by the presence of DBT, even with adequate control of hyperglycemia.In various clinical trials, the benefits of statins on cardiovascular disease and stroke in the DBT were demonstrated, indicating the pleiotropic anti -inflammatory properties of statins.

Fibrates play a beneficial role in people with DBT and very low HDL (& lt; 34 mg/dl) or very high triglycerides (205 mg/dl or more).Also, the proper treatment of hypertension in people with DBT is important, with the aim of achieving values ​​below 140/90 mm Hg.

The benefits of angiotensin converting enzyme inhibitors or angiotensin receptor blockers in patients with peripheral cerebrovascular or vascular disease were demonstrated.Hyperglycemia control with metformin to achieve levels of glycosylated hemoglobin below 7% proved to improve cardiovascular results.The benefits of antiplatelet therapy in established cardiovascular disease and acute coronary syndromes were demonstrated;But its role in peripheral vascular disease and DBT is less clear.

Conclusion

The interrelation of various factors in diabetic cardiovascular disease seems to reflect an increase in oxidative stress and inflammation that affect the vascular tree and multiple organs at the microvascular and macrovascular level;along with the harmful effects on the regional nervous system.

♦ SIIC - Ibero -American Society of Scientific Information