cardiovascular-agents and Diabetic-Neuropathies

Most of the late diabetic complications such as retinopathy, nephropathy, and neuropathy, have their basis in disturbed microvascular function. Structural and functional changes in the micro-circulation are present in diabetes mellitus irrespective of the organ studied, and the pathogenesis is complex. Endothelial dysfunction, characterized by an imbalance between endothelium-derived vasodilator and vasoconstrictor substances, plays an important role in the pathogenesis of diabetic microangiopathy. Increased circulating levels of endothelin-1 (ET-1), a potent vasoconstrictor peptide, has been found in patients with diabetes, and a positive correlation between plasma ET-1 levels and microangiopathy in patients with type 2 diabetes has been demonstrated. In addition to its direct vasoconstrictor effects, enhanced levels of ET-1 may contribute to endothelial dysfunction through inhibitory effects on nitric oxide (NO) production. Vascular endothelial dysfunction may precede insulin resistance, although the feature of insulin resistance syndrome includes factors that have negative effects on endothelial function. Furthermore, ET-1 induces a reduction in insulin sensitivity and may take part in the development of the metabolic syndrome. In the following, the mechanisms by which ET-1 contributes to the development of diabetic microangiopathy and the potentially beneficial effect of selective ET(A) receptor antagonists are discussed.

Topics: Cardiovascular Agents; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Endothelin Receptor Antagonists; Endothelin-1; Humans; Microcirculation; Receptors, Endothelin; Treatment Outcome; Up-Regulation

The aim of this article was to review the importance of the clinical identification of persons with cardiovascular autonomic neuropathy (CAN) and discuss potential treatment interventions.. A MEDLINE search was conducted for articles published during the last 20 yr. In addition, subsequent references of retrieved articles were reviewed. Search strategies included using key terms such as CAN, heart rate variability, orthostatic hypotension, and diabetes mellitus.. CAN is a common form of diabetic autonomic neuropathy and causes abnormalities in heart rate control as well as central and peripheral vascular dynamics. The clinical manifestations of CAN include exercise intolerance, intraoperative cardiovascular lability, orthostatic hypotension, painless myocardial ischemia, and increased risk of mortality. CAN contributes to morbidity, mortality, and reduced quality of life for persons with diabetes. The American Diabetes Association has recently published a statement that provides guidelines for prevention, detection, and management of neuropathy, including CAN, for healthcare providers who care for patients with diabetes. Algorithms for the evaluation and treatment of the patient with CAN, even if the patient is asymptomatic, are provided in this review.. Once CAN is identified in a patient with diabetes, healthcare providers may consider altering the prescribed exercise regimen, increasing surveillance for cardiac ischemia, carefully reexamining the list of prescribed medications, and aggressively treating cardiovascular risk factors (e.g. hypertension) that may be associated with the development of CAN.

Topics: Autonomic Nervous System Diseases; Cardiovascular Agents; Cardiovascular Diseases; Diabetic Neuropathies; Humans

Topics: Cardiovascular Agents; Chronic Disease; Diabetic Neuropathies; Diagnosis, Differential; Humans; Hypotension, Orthostatic

Diabetes mellitus as a disease of epidemiological impact leads to diabetic cardiopathy by modulation of myocardial, vascular and metabolic components. This includes the development of a coronary microangiopathy and a decrease of diastolic and systolic function of the left ventricle as well as the development of an autonomic diabetic neuropathy. Patients with diabetes show an increased mortality concerning cardiovascular events. They more often suffer from myocardial infarction as non-diabetics mostly with a more serious course. Moreover, the post-infarction course is affected with a worse prognosis as in non-diabetics. For diagnosis of cardial involvement in diabetes electrocardiographic and echocardiographic procedures are of use. Special tests of the autonomic function complete the diagnostic ensemble. An early therapy with ACE-inhibitors and beta blocking agents as well as a strong diabetes therapy, in particular with insulin, can influence the mortality favorably. Moreover, the diagnosis and therapy of additional cardiovascular risk factors (arterial hypertension, dyslipidemia) are very important, because these are correlated with a for diabetic patients markedly increased risk of mortality. The clinical relevance of the term diabetic cardiopathy is justified by the 6 factors: macroangiopathy, microangiopathy, disturbances of the myocardial metabolism, myocardial fibrosis, autonomic diabetic neuropathy and disturbances of the coagulability. Diagnostic and therapeutic goals are discussed.

Topics: Arteriosclerosis; Cardiovascular Agents; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Neuropathies; Diagnosis, Differential; Humans; Lipids; Myocardial Infarction; Risk Factors; Ventricular Dysfunction, Left

To clarify mildronate effects on oxidant stress and tissue oxygen in combined treatment of peripheral (sensomotor) neuropathy in patients with type 2 diabetes mellitus (DM).. An open randomized trial investigated 70 matched patients with type 2 DM and sensomotor neuropathy. They were randomized into two groups. The study group received basic anti-diabetic treatment, alpha-lipoic acid and mildronate for 3 months. Patients of the control group received the same treatment but mildronate.. Mildronate administration improved clinical condition of the study group patients vs controls by neuropathy and symptoms count scales, electrophysiological properties of the nerve fibers, optimization of oxygen tissue balance, reduced production of lipid peroxidation products and activated enzymes of antioxidant defense.. It is recommended to add 1 g/day mildronate to standard schemes of treatment for diabetes and sensomotor neuropathy.

Topics: Aged; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Fasting; Female; Humans; Male; Methylhydrazines; Middle Aged; Oxidative Stress

Previously, we had shown that a vasopeptidase inhibitor drug containing ACE and neprilysin inhibitors was an effective treatment for diabetic vascular and neural complications. However, side effects prevented further development. This led to the development of sacubitril/valsartan, a drug containing angiotensin II receptor blocker and neprilysin inhibitor that we hypothesized would be an effective treatment for diabetic peripheral neuropathy. Using early and late intervention protocols (4 and 12 weeks posthyperglycemia, respectively), type 2 diabetic rats were treated with valsartan or sacubitril/valsartan for 12 weeks followed by an extensive evaluation of vascular and neural end points. The results demonstrated efficacy of sacubitril/valsartan in improving vascular and neural function was superior to valsartan alone. In the early intervention protocol, sacubitril/valsartan treatment was found to slow progression of these deficits and, with late intervention treatment, was found to stimulate restoration of vascular reactivity, motor and sensory nerve conduction velocities, and sensitivity/regeneration of sensory nerves of the skin and cornea in a rat model of type 2 diabetes. These preclinical studies suggest that sacubitril/valsartan may be an effective treatment for diabetic peripheral neuropathy, but additional studies will be needed to investigate these effects further.

Topics: Aminobutyrates; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Animals; Biphenyl Compounds; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Diet, High-Fat; Disease Progression; Drug Combinations; Male; Neprilysin; Neural Conduction; Neuroprotective Agents; Protease Inhibitors; Rats, Sprague-Dawley; Tetrazoles; Valsartan; Vascular Resistance