Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Clinical studies have shown a relationship between diabetic retinopathy and vascular endothelial growth factor (VEGF) levels in ocular fluid. Advanced glycation end products (AGEs) have been implicated in diabetes complications, including diabetic retinopathy. Nepsilon-(carboxymethyl) lysine (CML) is a glycoxidation product that may be a marker of oxidative stress. In this study, we used enzyme-linked immunosorbent assays to determine the levels of VEGF, non-CML AGE and CML in the aqueous humor and serum of 82 Japanese patients with type 2 diabetes and 60 non-diabetic subjects. VEGF, non-CML AGE, and CML concentrations in aqueous humor and serum were then compared with the severity of diabetic retinopathy. Immunohistochemical detection analysis of non-CML AGE and CML was also performed using retinal tissues from patients with progressive diabetic retinopathy. Aqueous levels of VEGF, non-CML AGE and CML increased along with the progression of diabetic retinopathy compared to age-matched controls. After coagulation therapy, the VEGF, non-CML AGE, and CML levels were significantly reduced. Immunostaining showed diffuse co-localization of non-CML AGE and CML around microvessels and in the glial cells of proliferative membranes from patients with progressive diabetic retinopathy. These findings suggest that glycation and glycoxidation reactions (or oxidation, as revealed by CML) may contribute to both the onset and progression of diabetic retinopathy.
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PMID:Increased levels of vascular endothelial growth factor and advanced glycation end products in aqueous humor of patients with diabetic retinopathy. 1144 Feb 80

Ocular spectroscopy, which is the use of the eye to monitor optically the concentration of metabolites in the body, has been successfully applied to monitor aqueous humor glucose concentration. In the United States, 1.7 million intraocular lenses are currently implanted yearly. Because patients with diabetes are more likely to develop cataracts at an earlier age, a relatively high proportion of the patients receiving intraocular lenses have diabetes. Last year, 110,000 patients with diabetes received intraocular lens implants of various materials. We have successfully polymerized a fluorescent complex within a hydrogel intraocular lens that responds well to glucose concentration.
Diabetes Technol Ther 2000
PMID:Intraocular lens glucose sensor. 1146 16

The potential for the noninvasive measurement of blood glucose concentration to improve the level of blood sugar control and the quality of life of diabetic patients has been recognized for nearly 3 decades. Because of the many challenges involved in directly sensing glucose in the bloodstream noninvasively, the approach of noninvasive measurement of glucose concentration in the ocular aqueous humor, which reflects blood glucose concentration, has been likewise pursued over those 3 decades. Moreover, studies of the dynamic relationship between blood glucose concentration and ocular glucose concentration in both animals and humans suggest minimal latency between variations in blood glucose and those in ocular glucose. In a review of technological approaches to such measurements, the most promising techniques appear to be laser-based, and include laser polarimetry and Raman spectroscopy. Results for techniques such as multiwavelength polarimetry and Raman spectroscopy have been quite good, and it is likely that one or both of these techniques, possibly combined with refractive index measurement, will yield a useful instrument for both clinical use and patient self-monitoring.
Diabetes Technol Ther 1999
PMID:Laser-based measurement of glucose in the ocular aqueous humor: an efficacious portal for determination of serum glucose levels. 1147 84

In the recent past, several noninvasive optically based methods have been proposed for physiologic glucose sensing. One proposed optical sensing site has been the eye, which, due to its unique optical properties, can be considered as a transparent optical window into the body. In particular, the aqueous humor within the anterior chamber of the eye has been shown to contain glucose levels correlated to those of blood. Concern, however, has been expressed that using the aqueous humor solution as a measure of blood glucose may be problematic due to the potential transport time delay between the blood and the aqueous humor glucose concentrations. This investigation was performed to measure the transport time delay in a rabbit model. The time delay between the blood and aqueous humor glucose concentrations was measured invasively in five New Zealand White rabbits over a series of weeks. An anesthesia protocol containing the drug Xylazine was used to elevate the blood glucose levels to a level commonly seen in diabetic patients. The difference between the glucose peak location times occurring in the blood and aqueous humor glucose response was measured and defined as the transport time delay. The average transport time lag was measured to be under 5 min. This measured time delay indicates that, indeed, the eye could potentially be used as a sensing site for indirect blood glucose measurements and may eventually aid the development of a noninvasive glucose sensor due to its unique optical properties compared to other biological tissues.
Diabetes Technol Ther 2001
PMID:Measurement of the glucose transport time delay between the blood and aqueous humor of the eye for the eventual development of a noninvasive glucose sensor. 1147 26

Abnormal nitric oxide (NO) synthesis has been implicated in the pathogenesis of diabetes mellitus. The aim of our study was to elucidate the relationship between the stages of diabetic retinopathy (DR) and the NO levels in aqueous humor and plasma. Using the chemiluminescence assay, we measured the concentrations of NO in aqueous humor and plasma samples obtained during intraocular surgery from 45 diabetic patients and 19 nondiabetic cataract patients. The patients with diabetes were classified into 4 groups: proliferative DR (PDR) with active neovascularization (active PDR; 9 cases), PDR with quiescent neovascularization (regressed PDR; 6 cases), background DR (BDR; 16 cases) and no DR (14 cases). We found that the aqueous NO levels (mean +/- SE) of the active PDR group (83.2 +/- 13.9 microM) were significantly higher than those of the BDR group (45.8 +/- 6.0 microM, p = 0.049) and the diabetics without DR (33.3 +/- 5.2 microM, p = 0.011), and, although not statistically significantly, they were also higher than those of the regressed PDR group (52.1 +/- 10.3 microM, p = 0.224). However, no significant differences were observed between any of the diabetic subgroups in the plasma NO levels (p = 0.345). We therefore concluded that NO present in the ocular tissues may play important roles in the progression of DR.
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PMID:Possible involvement of nitric oxide in the progression of diabetic retinopathy. 1291 24

Retinopathy is the most common microvascular diabetes complication and represents a major threat to the eyesight. The aim of this study was to address the role of pro- and anti-angiogenic molecules in diabetic retinopathy in the aqueous humor of the eye. Aqueous humor was collected at cataract surgery from 19 diabetic patients and from 13 age- and sex-matched normoglycemic controls. Levels of pro-angiogenic vascular endothelial growth factor (VEGF) and angiogenic inhibitor pigment epithelium-derived factor (PEDF) were determined. Angiogenic activity of the aqueous humor was quantified by measuring its effect on the migration of capillary endothelial cells. In the aqueous fluid, VEGF levels were increased in diabetics (mean values: 501 vs. 367 pg/ml; p = 0.05), compared to controls. PEDF was found to be decreased in diabetics (mean values: 2080 vs. 5780 ng/ml; p = 0.04) compared to controls. In seven diabetic patients with proliferative retinopathy, the most profound finding was a significant decrease of the PEDF level (mean value: 237 ng/ml), whereas VEGF levels were comparable to diabetic patients without proliferation (mean value: 3153; p = 0.003). Angiogenic activity in samples of patients from the control group was generally inhibitory due to PEDF, and inhibition was blocked by neutralizing antibodies to PEDF. Likewise, in diabetics without proliferation, angiogenic activity was also blocked by antibodies to PEDF. We will demonstrate here that the level of the natural ocular anti-angiogenic agent PEDF is inversely associated with proliferative retinopathy. PEDF is an important negative regulator of angiogenic activity of aqueous humor. Our data may have implications for the development of novel regimens for diabetic retinopathy.
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PMID:Proliferative diabetic retinopathy is associated with a low level of the natural ocular anti-angiogenic agent pigment epithelium-derived factor (PEDF) in aqueous humor. a pilot study. 1292 Jun 63

IGF-1 has been associated with the pathogenesis of diabetic retinopathy, although its role is not fully understood. Here we show that normoglycemic/normoinsulinemic transgenic mice overexpressing IGF-1 in the retina developed most alterations seen in human diabetic eye disease. A paracrine effect of IGF-1 in the retina initiated vascular alterations that progressed from nonproliferative to proliferative retinopathy and retinal detachment. Eyes from 2-month-old transgenic mice showed loss of pericytes and thickening of basement membrane of retinal capillaries. In mice 6 months and older, venule dilatation, intraretinal microvascular abnormalities, and neovascularization of the retina and vitreous cavity were observed. Neovascularization was consistent with increased IGF-1 induction of VEGF expression in retinal glial cells. In addition, IGF-1 accumulated in aqueous humor, which may have caused rubeosis iridis and subsequently adhesions between the cornea and iris that hampered aqueous humor drainage and led to neovascular glaucoma. Furthermore, all transgenic mice developed cataracts. These findings suggest a role of IGF-1 in the development of ocular complications in long-term diabetes. Thus, these transgenic mice may be used to study the mechanisms that lead to diabetes eye disease and constitute an appropriate model in which to assay new therapies.
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PMID:Increased ocular levels of IGF-1 in transgenic mice lead to diabetes-like eye disease. 1508 94

Data obtained with the neutral red cytotoxicity assay reveal that human lens epithelial cells in culture are highly sensitive to low micromolar concentrations of unsaturated, cis-configured fatty acids in the following order: arachidonic acid>linolenic acid=linoleic acid=oleic acid, whereas the saturated fatty acids are much less effective. Though the cytotoxic effects of the unsaturated fatty acids could not be discerned from effects of their oxidation products, the fact that oleic acid is equally cytotoxic as linoleic acid or linolenic acid as well as previously reported findings with bovine lens epithelial cells support the idea that the unsaturated fatty acid molecules directly account for the cytotoxicity and not their products of lipid peroxidation. Bleb formation and cell retraction are early morphological signs of fatty acid-induced lens cell damage. These cellular alterations are accompanied by an aggregation of intermediate filaments in a first step, whereas the disorganization of microfilaments occurs at a later time and only at higher fatty acid concentrations. Measurements of protein-, RNA- and DNA-synthesis turned out to be much less sensitive parameters for the fatty acid-induced damage of lens cells. The uptake rate of linoleic acid by human lens cells is relatively high (4.35 fmol sec(-1) per 1000 cells), 30 and 50% higher as compared with diploid human embryonal lung fibroblasts and chemically transformed mouse fibroblasts, respectively. Saturation kinetics in combination with competition between linoleic acid, oleic acid and palmitic acid on one hand and ineffectiveness of trypsin and DIDS treatment on the other hand hint at cytoplasmic fatty acid binding proteins as receptors with high binding affinity (5.55 micromol l(-1), calculated for the linoleic acid-albumin complex) to be involved in the fatty acid uptake in human lens cells. Cellular fatty acid uptake is mainly influenced by the albumin concentrations present in physiological solutions. Albumin determinations in aqueous humor from 177 cataract patients reveal an age-dependent, statistically significant albumin rise with average values below 2 micromol l(-1) up to the age of 40 years to about 4 micromol l(-1) at the age between 80 and 90 years with single values up to 10 micromol l(-1). Using physiological fatty acid mixtures it is demonstrated that fatty acid-induced lens cell damage is strongly increased by elevated albumin concentrations found in aqueous humor of the elderly, who already have cataracts. Free fatty acid induced lens cell damage as a possible cause for age-dependent cataracts as well as a molecular link between systemic diseases such as diabetes and cataract formation is discussed.
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PMID:Fatty acid cytotoxicity to human lens epithelial cells. 1550 Aug 27

The total transforming growth factor (TGF) beta(2) concentration in the anterior chamber aqueous humor of 96 cataract patients with ages ranging from 17 to 88 years was measured using ELISA to investigate the changes that occur with age, difference of axial length, difference of localization of opacification of the cataractous lens and complications with other eye diseases. It was found that the total TGF-beta(2) concentration (1) decreases with age, (2) shows slight changes with axial length, (3) has slight changes with difference of localization of opacification, (4) is significantly high in patients with concurrent open-angle glaucoma (p < 0.05), (5) is high in patients with complicating diabetes who have undergone panretinal photocoagulation for diabetic retinopathy (p < 0.05) and (6) is low in patients with atopic cataracts. There have been several reports on point 4 above, but none to date of the other points. These findings provide useful information on the intraocular activity of TGF-beta(2).
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PMID:Concentration of transforming growth factor beta2 in aqueous humor. 1563 19


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