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

Diabetic cataract rarely concerns children. Its occurrence is usually caused by a genetic predisposition as well as a long-term decompensation of diabetes. Cases of cataract in children during the first year of diabetes are exceptional, therefore this case is presented. During the ophtalmological examination bilateral retrocapsular cataract was diagnosed in 12-year-old girl with an eleven-month history of diabetes type 1. Previous ophtalmological examination had not shown any abnormalities. The poor metabolic control of diabetes was observed during this time (avg. HbA1C - 8.2%).
 ...
PMID:[Diabetic cataract during the first year of diabetes - report of the case]. 1281 31

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.
 ...
PMID:Genetic analysis of aldose reductase in diabetic complications. 1287 Nov 35

Diabetes causes increased oxidative stress, which is thought to play an important role in the pathogenesis of various diabetic complications. However, the source of the hyperglycemia-induced oxidative stress is not clear. It was found that the polyol pathway is the major contributor to oxidative stress in the lenses and nerves of diabetic mice. The first enzyme in the pathway, aldose reductase (AR), reduces glucose to sorbitol, which is then converted to fructose by sorbitol dehydrogenase (SDH). Transgenic mice that overexpress AR specifically in their lenses showed a significant increase in oxidative stress when they became hyperglycemic, as indicated by a decrease in GSH and an increase in malondialdehyde in their lenses. Introducing an SDH-deficient mutation into these transgenic mice significantly normalized the GSH and malondialdehyde levels. These results indicate that both enzymes of the polyol pathway contributed to hyperglycemia-induced oxidative stress in the lens. In the wild-type mice, diabetes caused a significant decrease in GSH in their sciatic nerves, indicative of oxidative stress. In the AR null mutant mice, diabetes did not lead to any decrease in the nerve GSH level. These results indicate that similar to the situation in the lens, AR is also the major contributor to hyperglycemia-induced oxidative stress in the nerve. Although increased flux of glucose through the polyol pathway leads to diabetic lesions in both the lenses and nerve, the mechanisms may be different. AR-induced osmotic stress seems to be the cause of diabetic cataract, whereas AR-induced oxidative stress is probably the cause of neuronal dysfunction.
 ...
PMID:Contribution of polyol pathway to diabetes-induced oxidative stress. 1287 37

Fifty-eight (58) children with insulin-dependent diabetes mellitus (IDDM) were examined and shared between 6 groups: Group 1--primarily diagnosed diabetes mellitus (DM); Group 2--DM with an up to 5-year history; Group 3--DM with a an up to 10-year history; Group 4--children with non-proliferative diabetic retinopathy; Group 5--children with diabetic cataract. Forty-five healthy children were in the control group. According to the pattern registration of visual induced potentials (RVIP), a reliable prolongation of latency P100 was detected in children of Groups 1 and 4. The results of the general electroretinography (ERG) showed a reliably decreased amplitude of the basic wave b- in Groups 1-4 and an increased amplitude of wave a- in Groups 4 and 5. According to photopic ERG, a reliably decreased amplitude of wave a- was detected in Groups 1-5 and a decreased amplitude of wave b- was registered in all groups except for Group 2. Scotopic ERG showed, in Group 5, an increased amplitude of wave a- (p < 0.05) at the normal values of wave b-, and, in Groups 1-4,--a significantly inhibited amplitude of wave b-. Finally, rhythmic ERG showed a reliably inhibited amplitude in all groups.
 ...
PMID:[Changing electrophysiological parameters in the eye in children with insulin-dependent diabetes mellitus]. 1511 26

Cataract--opacification of the lens--is closely related to diabetes as one of its major late complications. This review deals with three molecular mechanisms that may be involved in the development of diabetic cataract: nonenzymatic glycation of eye lens proteins, oxidative stress, and activated polyol pathway in glucose disposition. Implications resulting from these mechanisms for possible pharmacological interventions to prevent diabetic cataract are discussed. The article reviews research on potential anticataract agents, including glycation inhibitors, antioxidants, and aldose reductase inhibitors. Information on possible benefits of putative anticataract agents comes from a variety of approaches, ranging from laboratory experiments, both in vitro and in vivo, to epidemiological studies in patients.
J Diabetes Complications
PMID:Pharmacological prevention of diabetic cataract. 1512 Jul 9

Investigations were carried out to clarify the role of autoimmune phenomena in the pathogenesis of human cataract. We determined the antibodies to lens proteins of serum in the following groups of patients: patients with senile cataract, patients with diabetic cataract, patients with diabetes mellitus, dependent of insulin and without cataract, patients without cataract and without diabetes mellitus (healthy adults), using the plate gel with double diffusion method described by Ouchterlony. 98% patients with senile cataract, 100% patients with diabetic cataract and only 12% healthy adults showed positive reactions to the test. There is little evidence so far, to incriminate immunological mechanisms in the pathogenesis of cataract.
 ...
PMID:[Antibodies against lens proteins in the blood in patients with cataract]. 1563 18

Previous studies have demonstrated that administration of pyruvate prevents cataract formation in diabetic rats. It is known that the induction of cataractous process in this case is initiated by aldose reductase (AR) catalyzed synthesis and accumulation of excessive sorbitol in the lens fibres and epithelium and their consequent osmotic hydration. Synthesis of this and other polyols is competitively inhibited by pyruvate. The objective of the present investigations was hence to determine whether pyruvate would have a similar protective effect in species where cataract formation is relatively independent of sorbitol synthesis such as in humans where the lens AR activity is extremely low, especially with glucose as a substrate. The Km of AR for glucose is known to be very high. The possible protective effect of pyruvate in the low AR models was conceived on the basis of our previous findings suggesting that it can also exert substantial antiglycating as well as antioxidant effects. The present studies have hence been conducted with mice, a species known to be low in lens AR, similar to that in humans. As stipulated, pyruvate administration has indeed been found to offer a significant protection against development of diabetic cataract in this model also. The effect correlated with the inhibition of protein glycation as well as of oxidative stress. The latter was apparent by the prevention of the loss of glutathione known to be associated with diabetes. Although there was a small but noticeable increment in the sorbitol content of the diabetic lenses, this was osmotically insignificant. Even this increase was prevented by pyruvate. The magnitude of the elevation in the contents of glycated proteins and the depression in the level of glutathione were, on the contrary, highly pronounced, suggesting a more prominent role of the latter factors. In addition, the possibility of a direct metabolic support it could offer to the tissue is also imminent by its effect on the maintenance of ATP, as shown earlier. The present studies are therefore considered more relevant to the pathogenesis of cataract in human diabetics and its possible prevention by endogenous compounds with antiglycating and antioxidant properties. Inhibition of cataract formation by pyruvate in an animal model with low lens AR, similar to that in humans, has been shown for the first time.
 ...
PMID:Prevention of cataract by pyruvate in experimentally diabetic mice. 1578 23

Hyperglycemia causes the autoxidation of glucose, glycation of proteins, and the activation of polyol metabolism. These changes accelerate generation of reactive oxygen species (ROS) and increases in oxidative chemical modification of lipids, DNA, and proteins in various tissues. Oxidative stress may play an important role in the development of complications in diabetes such as lens cataracts, nephropathy, and neuropathy. Glycation reactions, especially Maillard reactions, occur in vivo as well as in vitro and are associated with the chronic complications of diabetes mellitus and aging and age-related diseases by increases in oxidative chemical modification of lipids, DNA, and proteins. In particular, long-lived proteins such as lens crystallines, collagens, and hemoglobin may react with reducing sugars to form advanced glycation end products (AGEs). Recently, we found a novel type of AGE, named MRX, and we found that MRX is a good biomarker for detecting oxidative stress produced during Maillard reaction. We also examined in detail the role of lipid peroxidation reaction in hyperglycemia and found that hexanoyl modification formed by the reaction of oxidized lipids and proteins must be important for oxidative stress. Detailed analyses of the formation mechanism of hexanoyl lysine (HEL) moiety in proteins were conducted, and excretion of HEL into urine was quantified by using LC/MS/MS. Macrophages and neutrophils play an important role in oxidative stress during hyperglycemia, and we determined that oxidatively modified tyrosines are a good biomarker for formation of oxidative stress at an early stage. Immunochemical analyses by application of monoclonal antibodies specific to lipid hydroperoxide-modified proteins produced by polyunsaturated fatty acids including docosahexaenoic acid (DHA) in oxidative stress caused by hyperglycemia were conducted, and the relationship between glycation and lipid peroxidation reactions both by chemical and immunochemical approaches are discussed. Recently, we put much more focus on dietary antioxidants for prevention of diabetic complications. Curcuminoids, the main yellow pigments in Curcuma longa (turmeric), have been used widely and for a long time in the treatment of sprain and inflammation in indigenous medicine. Curcumin is the main component of turmeric, and two minor components are also present as the curcuminoids. Curcuminoids possess antioxidant activity. Protective effects of curcumin (U1) and one of its major metabolites, tetrahydrocurcumin (THU1), have been examined for development of diabetic cataract in 25% galactose-fed SD rats. Through detailed examination of protective mechanisms of THU1, it was found that THU1 showed that scavenger ROS not only formed during hyperglycemia, but also induced antioxidative enzymes including detoxification enzymes such as glutathine S-transferase. THU1 also showed significant increase of glutathione concentration in the cultured rat lens. Glutathione (gamma-glutamylcysteinyl glycine [GSH]) is thought to be an important factor in cellular function and defense against oxidative stress, and we found that dietary GSH suppresses oxidative stress in vivo in prevention of diabetic complications such as diabetic nephropathy and neuropathy.
 ...
PMID:Protective role of antioxidative food factors in oxidative stress caused by hyperglycemia. 1603 65

Primary implantation of intraocular lenses (IOLs) was made in 9 children (16 eyes) after removal of cataract; secondary implantation was performed in 2 children (4 eyes) 3 and 4 years after diabetic cataract aspiration. After surgery, 4, 4, and 3 children were followed up 1, 2, and 3 years, respectively. Thirteen cases of secondary cataract were observed after primary implantation (16 eyes); secondary cataract was recorded in 100% of cases after implantation of polymethyl methaacrylate IOLs and hydrophilic "Centrflex" lenses and only in 57.1% after implantation of hydrophobic "Acrysof" lenses. The visual acuity was 0.48 +/- 0.14 after removal of secondary cataract and 0.88 +/- 0.11 after laser discission. Laser invention did not lead to the progression or occurrence of diabetic retinopathy (DR) in the late periods of a follow-up. Cataract removal with IOL implantation in children with insulin-dependent diabetes (IDD) yields high functional results. The postoperative follow-up did not demonstrate a significant increase in the severity and incidence of DR, which seems to be associated both with a good postoperative IDD compensation and preventive treatment. The use of the hydrophobic flexible lenses is more optimal to prevent the development of secondary cataract.
 ...
PMID:[Results of surgical treatment for cataract with implantation of intraocular lenses in children with insulin-dependent diabetes mellitus]. 1640 63

Posterior capsular opacification (PCO) is the most common postoperative complication of contemporary cataract surgery. Limited information is available regarding PCO formation and factors that influence PCO development in the dog. Two hundred sixty-five eyes (144 from diabetic dogs and 121 from dogs with breed-related cataracts) were prospectively evaluated for PCO formation for up to 12 months postoperatively. The mean age of all dogs in the study was 7.77 years and diabetic dogs were significantly older than dogs with breed-related cataracts. There were 73 males (61 neutered, 12 intact) and 74 females (70 neutered, 4 intact) in the study. Statistical analysis was performed based on age, breed/size, gender, stage of cataract at the time of surgery, PCO score at each time point, breed-related vs. diabetic cataract, right eyes compared to left eyes, and presence/absence of uveitis. Age and gender did not significantly influence PCO formation. Small and medium-sized breeds developed significantly more PCO in comparison to the large/giant breeds at 2 weeks and 2-4 months postoperatively, but the differences were not significant at later time points. There was an overall significant increase in PCO formation in eyes with early immature cataracts when compared to other stages of cataract up to 4 months postoperatively but not at later time points. There were no statistical differences in PCO score at 6 months or at 1 year postoperatively in eyes with breed-related and diabetic cataracts. Right eyes did not differ from left eyes in PCO score. PCO score significantly increased over time in breed-related and diabetic groups and in the overall population. No difference was found in the degree of PCO formation in eyes with inflammation prior to or after surgery compared with those without inflammation. In summary, age, gender, presence of inflammation, and cause of cataract (breed-related vs. diabetes mellitus) do not influence the development of PCO in canine cataract dogs. Small and medium-sized breeds develop significant PCO earlier than larger breeds. It is important to note that all eyes from all dogs in this study developed PCO in a time dependent manner.
 ...
PMID:Posterior capsular opacification in diabetic and nondiabetic canine patients following cataract surgery. 1693 60


<< Previous 1 2 3 4 5 6 7 8 9 Next >>