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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macroangiopathy of the lower extremities is one of the most frequent complications of diabetes and has a very adverse impact on the quality of life of the patients. It affects approximately as much as half the diabetics with the duration of the disease for more than 15 years. It is encountered in two forms. The first type of affection--obliterating atherosclerosis--reminds of affections of the arteries of the lower extremities in the non-diabetic population, although some differences in the site of affection, morphology of sclerotic changes as well as the spectrum of risk factors were found, when compared with obliterating atherosclerosis in non-diabetics. Risk factors of this form of macroangiopathy include cholesterol, triacylglycerols, reduced values of HDL-cholesterol, hypertension, fibrinogen, smoking and apparently also albuminuria. The second form of macroangiopathy--mediocalcinosis--is not associated with the mentioned risk factors of atherosclerosis but is probably the consequence of diabetic neuropathy. Contrary to atherosclerosis, it does not lead to the development of obliteration but has also an adverse effect on the function of blood vessels. Its incidence correlates with the duration and compensation of diabetes as well as deteriorated perception of vibrations. With regard to the high incidence of gangrenes requiring amputation, it seems rational to influence in diabetics all known risk factors of macroangiopathy although convincing results of long-term intervention studies are still lacking.
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PMID:[Characteristics of diabetic macroangiopathy of the lower extremities]. 159 8

Late complications of diabetes mellitus include a variety of clinical pictures, mainly related to the involvement of the arterial wall both of large vessels (macroangiopathy) and small vessels (microangiopathy), and of the peripheral nervous system (neuropathy). Their presence in almost all types of diabetes indicates that there is a common pathogenetic mechanism, which can be substantially identified in high blood glucose levels and related alterations. Hyperglycemia, in fact, leads to some metabolic abnormalities, i.e. non-enzymatic glycosylation of proteins and polyol pathway activity; moreover it can negatively affect the pattern of some hormones, especially GH and sex steroids, and normal rheological and clotting properties of blood. These abnormalities, confirmed by experimental models, play a key role in the development of late diabetic complications. However some evidence indicates that a genetic background may predispose to their development or protect from their onset. The two main forms of diabetic retinopathy, non-proliferative and proliferative, show an incidence which increases with age and duration of diabetes, reaching 100% when diabetes lasts for more than 20 years. The risk of blindness, which is very high for the proliferative form, has been dramatically reduced by laser-photocoagulation. Diabetic nephropathy affects a lesser number of diabetics but, after a silent or preclinical stage, leads to renal failure and subsequent replacement therapy. Strict metabolic control in the silent stage and later rigid anti-hypertensive treatment can prevent or retard the evolution of this complication. A close association has been observed between diabetes and hypertension, which can directly affect the onset and evolution of diabetic nephropathy, probably through a common genetic mechanism. Diabetic neuropathy has a wide variety of clinical manifestations, at somatic, autonomic and central levels and can greatly modify the quality and expectancy of life. However, the major cause of death in diabetic subjects is large vessel disease or macroangiopathy, which is similar to non-diabetic atherosclerosis regarding the main histopathological and clinical manifestations but has a much higher prevalence and severity. Finally, a specific cardiomyopathy has also been described in diabetes mellitus and can account for the high rate of heart failure observed in these patients.
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PMID:The late complications of diabetes mellitus. 174 48

Ambulatory blood pressure monitoring can determine the average blood pressure level and the short- and long-term blood pressure variability (circadian rhythm). The circadian blood pressure rhythm appears to be mediated mainly by the circadian rhythm of the sympathetic tone which is linked to changes in physical and mental activity, e.g. the waking-sleeping cycle. A statistically significant circadian blood pressure rhythm was observed in approximately 80% of mild to moderate essential hypertensive patients as well as in normal subjects. However, in patients with Cushing's syndrome, under glucocorticoid treatment, or with hyperthyroidism, central and/or peripheral autonomic dysfunction (Shy-Drager syndrome, spinal cord injury, brainstem lesions, diabetic neuropathy, uremic neuropathy, etc), chronic renal failure, eclampsia, malignant hypertension, sleep apnea syndrome or systemic atherosclerosis, the normal circadian blood pressure rhythm appears to be eliminated or reversed, while in those with primary aldosteronism, renovascular hypertension, pheochromocytoma without paroxysmal hypertension, diabetes insipidus, acromegaly, hyperparathyroidism or hyperprolactinemia, the nocturnal blood pressure fall has been observed as in normal subjects. The alteration in the circadian blood pressure rhythm was observed with different pathophysiological conditions, although no specific pattern was observed for any condition. A disturbance in any part of the hierarchy of factors that regulate the circadian rhythm of sympathetic neural tone seems to disturb the circadian blood pressure rhythm. We conclude that ambulatory blood pressure monitoring is not critically important in the diagnosis of secondary hypertension although it does help in screening for secondary hypertension.
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PMID:Does ambulatory blood pressure monitoring improve the diagnosis of secondary hypertension? 208 1

Diabetics of both types suffer more frequently from atherosclerosis of the coronary, cerebral and peripheral arteries than the non-diabetic population of similar age groups. In the pathogenesis of atherosclerosis in diabetes an important part is played by the very frequent association of the diabetic syndrome with hyperlipoproteinaemia and hypertension, elevated levels of substances potentially toxic for the endothelium such as glucose, chylomicron remnants, sorbitol, immunocomplexes, CO and others. Changes of thrombocyte functions and of the equilibrium of the system prostacycline-thromboxane as well as disorders at different sites of the haemocoagulation an fibrinolytic cascade, no doubt, interfere in a negative way with the process of atherogenesis. Non-enzymatic glycosylation of various proteins probably is also of a certain importance for the process of atherogenesis. The genetic background of the individual has obviously an impact on atherosclerotic complications in diabetics of type 2 (U-allele) where potential atherogenic hyperinsulinaemia is one of the constant manifestations of the disease. The second form of macroangiopathy (mediocalcinosis) affects practically only diabetic subjects and is probably due to the denervation of the blood vessels of the extremities in diabetic neuropathy. Identification and influencing of risk factors of macroangiopathy could have a favourable effect on the quality of life and prognosis of diabetic patients.
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PMID:[Pathogenic aspects of diabetic macroangiopathy]. 221 67

The diabetic foot can be classified into the neuropathic foot, characterized by the neuropathic ulcer, the Charcot joint and neuropathic oedema associated with a good circulation, in which neuropathy predominates, and the ischaemic foot in which atherosclerosis is the dominant factor leading to a reduction in blood flow with absent pulses. In the neuropathic foot, blood flow is increased, the vessels are still and dilated as a result of medial wall calcification and there is evidence for arteriovenous shunting. The neuropathic ulcer characteristically develops on the plantar surface following inflammatory autolysis and haematoma formation under neglected callosities. Chiropody is therefore the mainstay of treatment and recurrence is prevented by redistribution of weight bearing forces by moulded insoles in special footwear. Charcot osteoarthropathy is often preceded by fracture which is a further complication of diabetic neuropathy and which precipitates the rapid bone and joint destruction of the Charcot joint. Neuropathic oedema responds to ephedrine with a reduction in peripheral flow and an increase in urinary sodium excretion. The ischaemic foot is characterized by rest pain, ulceration and gangrene. Medical management can be successful in up to 72%, the remainder needing arteriography to assess suitability for arterial reconstruction or angioplasty. In the diabetic leg, atherosclerosis is predominant in the branches of the popliteal artery making arterial reconstruction difficult. Optimum care of the diabetic foot is provided in a diabetic foot clinic where the skills of chiropodist, shoe-fitter and nurse receive full support from physician and surgeon. Many lesions of the diabetic foot are avoidable and thus patient education is the cornerstone of prevention.
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PMID:The diabetic foot: pathophysiology and treatment. 353 4

Reduced vagal activity assessed by heart rate variability (HRV) has been observed in studies of diabetics, but this association has not been reported at the population level. To investigate the association of HRV with diabetes mellitus, as well as fasting serum insulin, and glucose, we examined a stratified random sample of 1933 individuals (154 diabetics and 1779 non-diabetics), aged 45-65 years from the Atherosclerosis Risk in Communities (ARIC) study cohort. Two-minute, resting, supine beat-to-beat heart rate records were collected. Power spectral density estimation was used to derive HRV high frequency power (HF, 0.15-0.35 Hz) as the conventional marker of vagal function. Age, race, and gender-adjusted geometric means of HF were 0.78 and 1.27 (beat/min)(2) for diabetics and non-diabetics respectively (P for mean difference <0.01), reflecting a reduced vagal activity in diabetics. In individuals not diagnosed as diabetics, a graded, inverse association was observed between fasting serum insulin and HF (P for trend <0.01): the age, race, and gender-adjusted geometric mean values of HF in the lowest and highest quartiles of serum insulin were 1.34 and 1.14 (beat/minute)(2), respectively. A similar association was observed between glucose and HF in a univariate model, but not in the adjusted model. This first population-based study on this subject confirmed that diabetics have significantly lower vagal activity than non-diabetics. In individuals not diagnosed as diabetics, serum insulin, and, to a lesser degree, serum glucose were inversely associated with vagal function, suggesting a role in the pathogenesis of diabetic neuropathy.
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PMID:Association of vagal tone with serum insulin, glucose, and diabetes mellitus--The ARIC Study. 886 61

The polyol pathway is one of the possible biochemical mechanisms by which hyperglycemia could impair the function and structure of the cells affected by diabetic complications. As possible hypothesis for the pathogenesis of diabetic complications, the polyol osmotic theory, alterations in myo-inositol and sodium metabolism, intermediary metabolites, abnormal changes of the redox state (NADH/NAD+ ratio) and an abnormality of kinase C dependent protein phosphorylation have been proposed. Recently, increasing evidence suggests that glycation and oxidative stress may have a cross-link with polyol pathway, contributing to the development of diabetic complications. If hyperglycemia-induced polyol pathway hyperactivity has an important role in the etiology of late-onset diabetic complications, the inhibition of aldose reductase (AR), a rate-limiting enzyme of the pathway, could become a key element in the prevention and reversal of diabetic complications. Recent evidence from both animal experiments and clinical studies has emerged to support this theory, resulting in the development of drugs available for the clinical treatment of diabetic neuropathy. From the results obtained mainly in animal models of diabetic complications, it is well recognized at present that AR inhibitors have a positive inhibitory effect on neuropathy, retinopathy, nephropathy, keratopathy, cataract-formation, possibly infection and atherosclerosis. It is now clear that AR inhibitors may offer various benefits to patients with diabetic complications. However, more extensive efforts are needed for the evaluation of their effects.
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PMID:New concepts and insights on pathogenesis and treatment of diabetic complications: polyol pathway and its inhibition. 948 Oct 88

Atherosclerosis and endothelial dysfunction are responsible for the pathophysiologic basis of the spectrum of cardiovascular disorders including ischaemic heart disease (IHD), the leading cause of morbidity and mortality in the US. There have been major advances, including the use of pharmacotherapy, coronary and peripheral percutaneous transluminal interventions (PTI), coronary and peripheral bypass surgery and primary/secondary prevention measures. There are, however, multiple unmet needs: IHD refractory to medical therapy and unsuitable for revascularisation; critical limb ischaemia unsuitable for PTI or surgery; restenosis; ischaemic/diabetic neuropathy and heart failure. Cardiovascular gene therapy (GT) with vascular endothelial growth factor (VEGF) has yielded improved perfusion and reduced ischaemia in preclinical models of IHD. Several preclinical studies and Phase I and II clinical trials have shown the safety and therapeutic potential of GT in the treatment of IHD, peripheral arterial disease (PAD), restenosis, and ischaemic and diabetic neuropathy, pointing to the need for Phase III clinical trials.
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PMID:Gene therapy for cardiovascular angiogenesis. 1283 65

Sexual dysfunction is defined as "disturbances in sexual desire and in the psychophysiological changes that characterize the sexual response cycle and cause marked distress and interpersonal difficulty". The female sexual response cycle consists of three phases: desire, arousal, and orgasm. Various organs of the external and internal genitalia, e.g. vagina, clitoris, labia minora, vestibular bulbs, pelvic floor muscles and uterus, contribute to female sexual function. During sexual arousal, genital blood flow and sensation are increased. The vaginal canal is moistened (lubrication). During orgasm, there is rhythmical contraction of the uterus and pelvic floor muscles. Within the central nervous system, hypothalamic, limbic-hippocampal structures play a central role for sexual arousal. Sexual arousal largely depends on the sympathetic nervous system. Moreover, nonadrenergic/noncholinergic neurotransmitters (NANC), e.g. vasoactive intestinal polypeptide (VIP) and nitric oxide (NO), are involved in smooth muscle relaxation and enhancement of genital blood flow. Furthermore, various hormones may influence female sexual function. Estrogen has a significant role in maintaining vaginal mucosal epithelium as well as sensory thresholds and genital blood flow. Androgens primarily affect sexual desire, arousal, orgasm and the overall sense of well-being. The internationally accepted classification of female sexual dysfunction consists of hypoactive sexual desire disorders, sexual aversion disorders, sexual arousal disorders, orgasmic disorders and sexual pain disorders. Vascular insufficiency, e.g. due to atherosclerosis, and neurologic diseases, e.g. diabetic neuropathy, are major causes of sexual dysfunction. Additionally, sexual dysfunction may be due to changes in hormonal levels, medications with sexual side effects or of psychological origin. For the diagnosis of female sexual dysfunction, a detailed history should be taken initially, followed by a physical examination and laboratory studies. Physiologic monitoring of parameters of arousal potentially allows to diagnose organic diseases. Recordings at baseline and following sexual stimulation are recommended to determine pathologic changes that occur with arousal. Duplex Doppler sonography, photoplethysmography or the measurement of vaginal and minor labial oxygen tension may help to evaluate genital blood flow. Moreover, measurements of vaginal pH and compliance should be performed. Neurophysiological examination, e.g. measurement of the bulbocavernosus reflex and pudendal evoked potentials, genital sympathetic skin response (SSR), warm, cold and vibratory perception thresholds as well as testing of the pressure and touch sensitivity of the external genitalia, should be performed to evaluate neurogenic etiologies. Medical management of female sexual dysfunction so far is primarily based on hormone replacement therapy. Application of estrogen results in decreased pain and burning during intercourse. The efficacy of various other medications, e.g. sildenafil, L-arginine, yohimbine, phentolamine, apomorphine and prostaglandin E1, in the treatment of female sexual dysfunction is still under investigation.
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PMID:[Female sexual dysfunction: a systematic overview of classification, pathophysiology, diagnosis and treatment]. 1588 Sep 11

Erectile dysfunction (ED) is commonly associated with risk factors for cardiovascular disease, including diabetes. The prevalence of ED in diabetic patients is high--about 75% of diabetic men 60 yr of age or older had ED in one study. Endothelial dysfunction, accelerated atherosclerosis, and diabetic neuropathy likely contribute to ED in diabetics. As silent ischemia is common in the diabetic patient, and diabetes is now often thought of as a coronary heart disease risk equivalent, diabetic men seeking therapy for ED may be considered candidates for exercise stress testing. Phosphodiesterase 5 (PDE5) inhibitors improve erectile function in diabetic men with ED; however, efficacy rates may be somewhat lower than in nondiabetic men. Studies to date have suggested that PDE5 inhibitors per se do not cause an increase in myocardial infarction rates in men being treated for ED.
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PMID:Assessment of cardiovascular risk in patients with erectile dysfunction: focus on the diabetic patient. 1514 90


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