Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The evidence of sorbitol excess in the crystalline lens of alloxan-diabetic rats has led to anticipate the role of the enzyme aldose-reductase in the pathogenesis of the diabetic cataract. In addition, a number of experimental works have more recently shown the involvement of myoinositol deficiency, which probably results from the sorbitol accumulation. These metabolic pathways are most likely implicated in the pathogenesis of diabetic neuropathy and perhaps additionally in that of microangiopathy. The synthesis of several aldose-reductase inhibitors (AR inhibitors) confirmed experimentally these hypothesis. By reducing the activity of the enzyme aldose-reductase, these substances suppress the adverse metabolic consequences of polyol accumulation, myositol deficiency and dysfunction of the Na+/K+ ATPase dependent sodium activity. Although different experimentations showed that the AR inhibitors could prevent in animals the development of experimental cataract as well as the early functional or later anatomic abnormalities of the diabetic retinopathy and nephropathy, the clinical trials did not clearly support these experimental results in humans. On the other hand, the AR inhibitors were proved to exhibit some efficacy in the early stage of diabetic neuropathy and in incipient nephropathy where they delay the development of albustix positive proteinuria. However, the benefit of an early treatment with AR inhibitors should be confirmed by long term prospective studies, which could also assess the safety of these drugs in chronic administration.
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PMID:[Role of polyols in the development of diabetic complications. Value of aldose-reductase inhibitors]. 141 Aug 79

A personal series of 6780 patients with diabetes mellitus is reported. Of these 1410 were thought to have insulin-dependent (Type 1) diabetes and 4926 non-insulin-dependent (Type 2) diabetes. Among the former, 128 patients were only diagnosed when in severe ketoacidosis or coma. In 116 patients the diabetes was diagnosed in pregnancy. Chronic alcoholism was an aetiological factor in 75 patients; in 52 it led to the diagnosis being made, and it complicated treatment in 129 additional patients. In the patients with Type 2 diabetes whose treatment was stabilized 23.5% were having insulin injections, 44.5% tablets, and 32.0% diet only. Sight-threatening retinopathy developed in 21.3% of patients with Type 1 and 7.9% of those with Type 2 diabetes. The rate of developing sight-threatening retinopathy was 1.1% of patients per year. Blindness occurred in 0.28% of patients with Type 1 diabetes per year and 0.097% per year in Type 2 diabetes. If the mean survival of patients with retinopathy going blind is 7.5 years, this would mean 7500 people in the UK blind from diabetic retinopathy. There was a striking drop in the annual incidence of blindness after 1970 coinciding with the introduction of specific treatment for diabetic retinopathy. Juvenile cataract developed in 1.7% of patients who developed Type 1 diabetes before 30 years of age. Clinically important diabetic neuropathy developed in 17.4% of patients with Type 1 and 11.6% of those with Type 2 diabetes. The main features were paraesthesiae and numbness (49%), neuropathic ulceration (37%), pain (5%), autonomic symptoms (5%), and amyotrophy (4%). Oculomotor palsies and mononeuropathies were noted. Foot ulceration occurred in 81 patients with Type 1 and 279 of those with Type 2 diabetes. Charcot changes in the feet were noted in 21 patients. Major amputations were needed in 18 patients with Type 1 and 60 with Type 2 diabetes. Proteinuria believed to be due to diabetic nephropathy developed in 12.8% of patients with Type 1 and 4.7% of those with Type 2 diabetes. The prevalence of early renal failure was 4.6% and 1.4%, respectively. Coronary artery disease was noted in 9% of patients with Type 1 diabetes, and was more common in those who developed diabetes after 20 years of age. Myocardial infarction was as common in women as in men. In Type 2 diabetes coronary artery disease gave rise to symptoms in 19.1%, and myocardial infarction was more common in men.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Diabetes in the United Kingdom: a personal series. 182 47

The activity of the polyol pathway--a non insulin-dependent metabolic pathway of glucose--is increased in diabetic patients. Polyol accumulation is involved, by a myoinositol-dependent mechanism, in the pathogenesis of some degenerative complications of diabetes. Thus, sorbitol accumulation in the eye lens and in nerves seems to be an important factor in the development of cataract and in the slowing down of nerve conduction. Recent studies suggest that the polyol pathway may play a role in early structural abnormalities of retinal and renal microangiopathy. Synthetic aldose reductase inhibitors could be used for a physiopathogenic treatment of these complications, but the first trials in diabetic neuropathy proved disappointing. Further studies, prolonged and well controlled, are necessary to pronounce on the future of this new category of drugs.
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PMID:[Role of the polyol pathway in the occurrence of degenerative complications of diabetes]. 301 8

Polyhydric alcohols (polyols) are widely distributed in nature, and the enzymes of the polyol pathway (aldose reductase and sorbitol dehydrogenase) are present in many mammalian tissues. The function of this pathway remains a mystery. A primary role for the pathway in the pathogenesis of 'sugar cataract' was provided by a number of experimental observations and in the 1960s the 'osmotic hypothesis' was propounded. This hypothesis also had implications for the pathogenesis of diabetic neuropathy. However, in the 1970s doubts were raised about the validity of the hypothesis, culminating in experiments which suggested that abnormalities in myo-inositol metabolism in nerve and lens were more closely related to the glucose-induced functional changes in these tissues than was the polyol pathway. Nevertheless, increased activity of the polyol pathway must still be regarded as an instigator of the biochemical abnormalities that lead to damage of lens and nerve in diabetes mellitus.
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PMID:The polyol pathway. A historical review. 379 30

The clinical and electro-neurographic examinations were carried out in 54 patients aged 21-67 years (mean = 41.8) with IDDM of at least 10-year duration, and 25 subjects aged 19-62 years (mean = 39.0) as a control group. The aim of the study was the determination of: 1) the frequency of polyneuropathy appearance in patients with IDDM of at least 10-year duration; 2) the usefulness of electroneurography for detection of subclinical impairment of peripheral nervous system in diabetics; 3) the characterization of electro-neurographic abnormalities in diabetic neuropathy; 4) the influence of diabetes duration and metabolic control on severity of peripheral nerves affection; 5) the relationship between polyneuropathy and retinopathy, nephropathy and cataract occurrence in diabetic patients. Polyneuropathy was diagnosed--clinically in 67% of patients, electro-neurographically in 85% of patients. The neurographic study proved high sensitivity for detection of subclinical affection of peripheral nerves in diabetics. The electro-neurographic abnormalities appeared more frequently and were more considerable in the group of patients with clinical polyneuropathy. Frequency of the sensory and motor nerve fibres involvement was similar. The electroneurographical abnormalities corresponded with the features of mixed--axonal and demyelinating type of neuropathy. It was disclosed that the degree of neurographical changes did not depend on duration and severity of hyperglycemia in late period of the disease. A moderate relationship between occurrence of polyneuropathy and retinopathy, nephropathy as well as diabetic cataract was revealed.
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PMID:[Clinical and electroneurographic changes in the peripheral nervous system of patients with chronic insulin-dependent diabetes (IDDM)]. 750 45

The prevalence of diabetic ocular complications and the correlation between diabetic retinopathy and systemic factors were examined in 2,300 cases (4,600 eyes) with non-insulin-dependent diabetes mellitus. The prevalence of cataract was 66.7%, of retinopathy 37.0%, of refractive and accommodative change 6.2%, of glaucoma 1.9% (rubeotic glaucoma was 1.0%), of rubeosis iridis 1.5%, of iridocyclitis 0.8%, of extraocular muscle palsy 0.2%, and of ischemic optic neuropathy 0.1%. Duration of diabetes mellitus, HbA1C value, methods of diabetic control, age, diabetic nephropathy, diabetic neuropathy, hypertension, systolic blood pressure, diastolic blood pressure, and arteriosclerosis obliterans were related with diabetic retinopathy. We suggest that the management of diabetic patients needs sufficient attention in the cases with oral administration of medication, insulin therapy, and diabetic nephropathy.
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PMID:[Prevalence of diabetic ocular complications and systemic factors]. 836 83

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

Postural stability in 55 non-insulin dependent diabetics was compared with 53 non-diabetic controls matched for age and gender. The study was conducted in a primary care clinic, using a computerised postural sway system. Changes in the centre of pressure while the subjects stood on a force platform were recorded, and sway parameters computed using customised software. Clinical data were obtained by interview, physical examination, and from case records. Results of the study showed that non-insulin dependent diabetics were more unstable than the non-diabetic controls for four out of the six parameters studied (namely L, length of sway path; Vel, average speed of centre of pressure along its path; Ao, area included within the path of the centre of pressure; and Ae, 95% confidence elliptical area), after adjusting for height, weight, adequate sleep and alcohol intake the night before, and history of bone or thyroid disorders. Amongst diabetic subjects, significant factors associated with postural stability were age, weight, presence of peripheral neuropathy or cataract, metformin, use, and HbAlc levels > 9%. Further studies are indicated to look into factors affecting postural stability (other than diabetic neuropathy) in greater depth.
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PMID:Postural stability in non-insulin dependent diabetics. 952 70

Diabetes complications, especially late (chronic) ones, are the main reasons of invalidity and early mortality. The most threatening diabetes complications are vascular and metabolic complications (diabetic neuropathy, angiopathy, cataract, glaucoma, optic neuropathy, retinopathy, diabetic nephropathy). Good diabetes control is very important, because in early stages these changes are reversible. In order to decrease the number of diabetes complications and to postpone their development, the use of biologic active components and plants is recommended. The most important biologic active substances for this purpose are vitamins and minerals, proteins, polysaccharides, lectins, saponins and flavonoids. According the scientific data, the mostly used plants are: Ginkgo biloba, Allium sativum, Silybum marianum, Panax Ginseng, Carica papaya, Vaccinium myrtillus, Phaseolus vulgaris. Some of them are proposed for treatment of symptoms related to venous and lymphatic vessel insufficiency, for the prophylaxis and treatment of liver damage caused by metabolic toxins, in chronic degenerative liver conditions, for the therapy of digestive disorders, to increase in the unspecific way the resistance of the organism to various environmental influences, and to stabilize membranes through antioxidant and radical scavenging actions.
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PMID:[Importance of biologically active components and plants in the prevention of complications of diabetes mellitus]. 1253 4

Diabetes Mellitus is an increasing concern, worldwide in terms of health. Long-term diabetes often leads to secondary diseases such as cataract, retinopathy, neuropathy, nephropathy, and cardiovascular diseases. The enzyme aldose reductase (AR) has been implicated in the pathogenesis of some of these diseases and inhibitors of AR (ARIs) were effective in preventing some of the diabetic complications in animal models. However, clinical trials of these drugs were disappointing, casting doubt on the role of AR in these diseases. This review focuses on the recent studies using transgenic and gene knockout mice to analyze the role of AR in diabetic cataract and neuropathy. These studies clearly demonstrated that AR is crucial to the pathogenesis of these diseases, and that the mechanism leading to diabetic cataract may be different from that which causes diabetic neuropathy. A number of studies showed that there is a correlation between AR gene markers and susceptibility to develop complications among diabetic patients, suggesting that AR is also involved in the pathogenesis of diabetic complications in human. Together, these genetic studies strongly indicate that AR is an important target for the prevention of diabetic complications in human. This may provide impetus to develop more effective ARIs and to conduct better-designed clinical trials for ARIs in the prevention and treatment of these diseases.
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PMID:Genetic analysis of aldose reductase in diabetic complications. 1287 Nov 35


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