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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The morphologically distinct diabetic or 'metabolic' cataract is rare in newly diagnosed insulin dependent diabetes. The cases described are of five adolescents (three girls, two boys) with newly diagnosed insulin dependent diabetes who developed metabolic cataracts close to the time of diagnosis (0-16 months). They all had a prolonged duration of symptoms before diagnosis (4-24 months) and high glycated haemoglobin levels at diagnosis (15-21%). The pathogenesis of diabetic cataract is not well understood in humans. An attempt is made to link clinical observations with evidence from experimental animal models to understand the mechanism of cataract formation, with particular reference to the aldose reductase pathway. It is recommended that the lens and retina are examined at the onset of diabetes in all children, especially those who have a prolonged duration of symptoms before diagnosis and who report persistent blurred vision.
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PMID:Metabolic cataracts in newly diagnosed diabetes. 906 99

There is strong evidence to show that diabetes is associated with increased oxidative stress. However, the source of this oxidative stress remains unclear. Using transgenic mice that overexpress aldose reductase (AR) in their lenses, we found that the flux of glucose through the polyol pathway is the major cause of hyperglycemic oxidative stress in this tissue. The substantial decrease in the level of reduced glutathione (GSH) with concomitant rise in the level of lipid peroxidation product malondialdehyde (MDA) in the lens of transgenic mice, but not in the nontransgenic mice, suggests that glucose autoxidation and nonenzymatic glycation do not contribute significantly to oxidative stress in diabetic lenses. AR reduction of glucose to sorbitol probably contributes to oxidative stress by depleting its cofactor NADPH, which is also required for the regeneration of GSH. Sorbitol dehydrogenase, the second enzyme in the polyol pathway that converts sorbitol to fructose, also contributes to oxidative stress, most likely because depletion of its cofactor NAD+ leads to more glucose being channeled through the polyol pathway. Despite a more than 100% increase of MDA, oxidative stress plays only a minor role in the development of cataract in this acute diabetic cataract model. However, chronic oxidative stress generated by the polyol pathway is likely to be an important contributing factor in the slow-developing diabetic cataract as well as in the development of other diabetic complications.--Lee, A. Y. W., Chung, S. S. M. Contributions of polyol pathway to oxidative stress in diabetic cataract. FASEB J. 13, 23-30 (1999)
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PMID:Contributions of polyol pathway to oxidative stress in diabetic cataract. 987 26

The protective effect of taurine in model in vitro diabetic cataract and the mechanism of this effect were investigated in isolated rat lenses. Isolated rat lenses were incubated in medium 199 in elevated glucose (55.6 m m) with taurine (5 m m). Taurine concentrations in the lenses were determined by amino acid analysis. Accumulative leakage of the intracellular enzyme lactate dehydrogenase (LDH) was used to estimate damage to the lens, as previously reported. In the clear lenses, prior to vacuole formation, after 1 or 2 days of incubation, the taurine and amino acids in lenses decreased progressively in concentration. In lenses incubated with 5 m m taurine, the level of taurine was increased towards that of control lenses. In taurine-treated lenses LDH leakage was significantly decreased, and lens clarity was maintained, similarly to that found previously for vitamin C and lipoic acid. To test whether taurine has similar antioxidant activity, we tested its ability to decrease luminol luminescence generated by (1) superoxide from hypoxanthine/xanthine oxidase and (2) peroxide from diluted glucose/glucose oxidase. For either superoxide or peroxide, the luminescence was decreased to zero, as a function of increasing taurine concentration, at 30 m m, approximately the physiological concentration of taurine in the lens. Spin trapping confirmed that taurine scavenged superoxide. This is consistent with a role for taurine as an important antioxidant protecting the lens against oxidative insults. Amino acids also had antioxidant activity in this assay, and as a group, when all activities were summed, their loss also contributed significantly to the antioxidant loss. Taken in conjunction with Wolff and Crabbe's observation of increased free radical generation by glucose auto-oxidation in diabetes, this suggests a push-pull mechanism for increased oxidative stress in diabetic cataract, involving both increased free radicals and decreased radical scavenging antioxidants.
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PMID:Modelling cortical cataractogenesis 22: is in vitro reduction of damage in model diabetic rat cataract by taurine due to its antioxidant activity? 1047 37

Diabetes mellitus is one of the most common endocrinopathies in the dog and cat. Diabetic cataract primarily affects the canine species and is rarely observed in the cat. It has been proposed that the incidence of cataracts in diabetic dogs is high because many of these patients have significant hyperglycemia despite insulin therapy. Age, gender, levels of serum glucose (before and during insulin therapy) and cataract formation were evaluated, retrospectively, in 23 dogs and 22 cats with diabetes mellitus. In the canine population, the groups with the highest frequency of presentation were females and sexually intact animals. In contrast, males and neutered animals were the most prevalent groups in the feline diabetic population. Over 80% of diabetic cats and dogs were older than 7 years. Our results confirm the almost total lack of cataracts in diabetic cats, while they were present in more than half of the dogs. A relation between the incidence of cataracts and the correspondent level of hyperglycemia in the canine and feline species could not be established. The estimation of the relative risk for the development of cataracts in diabetic dogs shows that some population groups have a higher probability for suffering from this ocular alteration. A relation between relative risk and the correspondent level of hyperglycemia in the various groups was not found. This fact indicates that other factors are involved in the unequal appearance of diabetic cataracts in dogs and cats.
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PMID:Diabetic cataracts: different incidence between dogs and cats. 1089 2

Some mechanisms have been proposed for cataract formation in diabetes mellitus such as excessive tissue sorbitol concentrations, abnormal glycosylation of lens proteins and increased free radical production in the intraocular region. We measured total antioxidant status and uric acid levels in aqueous humor from diabetic (n=20) and non-diabetic subjects (n=16) with cataracts. The patients with diabetes and cataract had significantly lower aqueous humor total antioxidant status than those with senile cataract (p = 0.001). Serum and aqueous humor uric acid levels were significantly lower in the diabetic cataract group compared to the senile cataract group. In the diabetic cataract group, the aqueous humor antioxidant status correlated positively with the aqueous humor uric acid levels (p < 0.05). The results of this study suggest that reduced aqueous humor antioxidant status might be associated with reduced aqueous humor uric acid in patients with diabetic cataract. This decrease in aqueous humor uric acid levels might lead to the acceleration of cataract formation.
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PMID:Diabetic cataract and the total antioxidant status in aqueous humor. 1134 48

The objective of the study was to determine the incidence and estimated median time to cataract formation in dogs with diabetes mellitus. The animals studied were 200 dogs with diabetes mellitus which were referred to a university teaching hospital between 1985 and 1995. Medical records from dogs with a diagnosis of diabetes mellitus were reviewed and, where necessary, further follow-up information was gathered from the referring veterinarian. Incidence rate and median time to diabetic cataract formation was calculated using survival-analysis techniques in a retrospective cohort study design. Among the 200 dogs in the study population, 23 had cataracts at the time of diabetes diagnosis that were presumed to be related to other disease processes. Of the remaining 177 dogs, 132 had documented cataract development with features suggestive as being secondary to diabetes. Twenty-three dogs did not have obvious cataracts at the time of their last examination while 22 dogs did not have cataracts at the time they were lost to follow-up. These 55 cases contributed to the statistical models as noncases of cataracts until the last date for which an examination was available. Half of the population had developed cataracts by the 170th day postdiagnosis of diabetes mellitus, while 75% and 80% of the population developed cataracts by 370 days and 470 days, respectively. The results of this study suggest that the majority of dogs with diabetes will develop cataracts within 5-6 months from the time of diagnosis of the disease, and that approximately 80% of dogs will develop cataracts within 16 months of diagnosis.
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PMID:A retrospective-cohort study on the development of cataracts in dogs with diabetes mellitus: 200 cases. 1139 60

The relationship between the polyol pathway and sugar cataracts has been studied extensively using streptozotocin-induced diabetic rats and galactose fed rats as animal models for insulin-dependent diabetes mellitus (IDDM). In these models, sugar cataracts progress quickly, leading to rapid lenticular polyol accumulation in the early stages of cataract formation. In 1992, a new animal model of non-insulin-dependent diabetes mellitus (NIDDM), the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, was established. In the present study, we examined both biochemical and morphological changes in the lenses of the OLETF rats to determine whether these changes reflect those associated with diabetic cataract formation and to clarify their relationship with the polyol pathway. For the biochemical analysis, we measured the enzyme activity of aldose reductase (AR) and sorbitol dehydrogenase (SDH) and the sorbitol levels using 20, 40 and 60 week old OLETF or control Long-Evans Tokushima Otsuka (LETO) rats. Enzyme activities of AR and SDH, which were lower in 20 week old OLETF rats than in LETO rats, were increased in 60 week old OLETF rats. The lenticular sorbitol level of the OLETF rats was similar to the control level at 20 weeks of age, but it was markedly increased at 40 weeks of age, and slightly decreased at 60 weeks of age compared with rats at 40 weeks but not compared with controls. Slight lens fiber swelling was observed in the anterior and/or posterior subcapsular regions of 40 week old OLETF rats, accompanying elevated sorbitol level and slightly increased SDH activity in the lens. Swelling and liquefaction of lens fibers were observed in the subcapsular and supranuclear region of 60 week old OLETF rats, as well as decreased lenticular sorbitol, and markedly increased SDH activity compared with rats at 40 weeks. AR activity was also increased causing the elevation of sorbitol in lenses of OLETF rats during the early stages of cataract formation. Despite differences in the etiology of diabetes mellitus, the strain of rat and the rate of disease progression in the OLETF rat model compared with other diabetic models, the present results support the theory that the polyol pathway via AR is a factor in the development of sugar cataracts.
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PMID:Biochemical and morphological changes during development of sugar cataract in Otsuka Long-Evans Tokushima fatty (OLETF) rat. 1152 Jan 12

Total and 12 individual proteins were measured in the lacrimal fluid of children and adolescents with insulin-dependent diabetes mellitus. Lacrimal excretion of proteins helps diagnose the preclinical, nonproliferative, and preproliferative stages of diabetic retinopathy and predict the course of diabetic cataract.
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PMID:[Protein markers of diabetic retinopathy]. 1185 46

To determine the involvement of calpains in human cataractogenesis, studies in aged animal models are needed. Aged, male WBN/Kob rats spontaneously develop cataract along with severe, persistent diabetes with hyperglycemia and nephropathy. The purpose of present experiments was to provide a biochemical mechanism for the involvement of ubiquitous calpains in cataractogenesis in WBN/Kob rats. Serum and urinary glucose were measured to confirm diabetes, and cataracts were observed by slit lamp biomicroscopy. Calcium determinations were performed on lens samples from several ages of WBN/Kob and Wistar rats. Casein zymography, immunoblot analysis for alpha-spectrin, calpain 2, and calpain 10 were performed to detect activation of calpain in lens samples. Serum glucose levels increased and cortical cataract developed in male WBN/Kob rats within 1 year, indicating diabetic cataract. Cataract was accompanied by several presumptive biochemical indicators of calpain activation, including increased calcium, proteolysis of alpha-spectrin, and decreased caseinolytic activity for calpains suggesting calpain activation followed by autolytic degradation. Activation of ubiquitous calpains may contribute to biochemical mechanism of cataractogenesis in spontaneously diabetic WBN/Kob rats. The WBN/Kob model may be useful for elucidating the roles of calpain 2 and calpain 10 in human cataractogenesis.
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PMID:Contribution of ubiquitous calpains to cataractogenesis in the spontaneous diabetic WBN/Kob rat. 1245 73

The purpose of the present study was to investigate the suitability of using the mouse, a species known to have a low lens aldose reductase activity, as a model animal for studying the pathogenesis of diabetic cataract. Earlier studies with diabetic rats whose cataract development is much faster can only partially explain the etiology of cataracts in humans where lens aldose reductase is substantially low. CD-1 mice were injected intraperitoneally with streptozotocin according to Rossini's method. Blood glucose levels were estimated after 7 days, and animals having blood glucose between 300 and 400 mg/dl were selected for further experiments. Development of lenticular opacity was followed by examining the animals every 3-4 weeks by direct ophthalmoscopy, slitlamp examination and Scheimpflug photography. Additionally, the animals were sacrificed at appropriate intervals, eyes enucleated and subjected to morphological studies. The presence of refractive changes and early cataract in the diabetic mice was initially ascertained by the distorted appearance of the grid pattern when seen through the isolated lenses. Early cataracts were visible on slitlamp examination and by ophthalmoscopy as early as 3-4 weeks after the establishment of diabetes. Advanced opacity was clearly documentable by photography after 5-6 months. Similar to that in other species, a single layer of anterior epithelial cells abutting the anterior capsule was seen in the histological sections of normal mouse lenses. On the contrary, the epithelium in the diabetic lens was multilayered, and numerous nucleated cells were visible in the superficial anterior cortex. These studies therefore suggest that further studies with mice may throw additional light on the contribution of diabetes in the pathogenesis of cataracts in low lens aldose reductase models.
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PMID:Establishment of the mouse as a model animal for the study of diabetic cataracts. 1256 58


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