beta-carotene and Diabetic-Retinopathy

To determine whether screening for age-related macular degeneration (AMD) during a diabetic retinopathy (DR) screening program would be cost effective in Hong Kong.. We compared and evaluated the impacts of screening, grading, and vitamin treatment for intermediate AMD compared with no screening using a Markov model. It was based on the natural history of AMD in a cohort with a mean age of 62 years, followed up until 100 years of age or death.. Subjects attending a DR screening program were recruited.. A cost-effectiveness analysis was undertaken from a public provider perspective. It included grading for AMD using the photographs obtained for DR screening and treatment with vitamin therapy for those with intermediate AMD. The measures of effectiveness were obtained largely from a local study, but the transition probabilities and utility values were from overseas data. Costs were all from local sources. The main assumptions and estimates were tested in sensitivity analyses.. The outcome was cost per quality-adjusted life year (QALY) gained. Both costs and benefits were discounted at 3%. All costs are reported in United States dollars ($).. The cost per QALY gained through screening for AMD and vitamin treatment for appropriate cases was $12,712 after discounting. This would be considered highly cost effective based on the World Health Organization's threshold of willingness to pay (WTP) for a QALY, that is, less than the annual per capita gross domestic product of $29,889. Because of uncertainty regarding the utility value for those with advanced AMD, we also tested an extreme, conservative value for utility under which screening remained cost effective. One-way sensitivity analyses revealed that, besides utility values, the cost per QALY was most sensitive to the progression rate from intermediate to advanced AMD. The cost-effectiveness acceptability curve showed a WTP for a QALY of $29,000 or more has a more than 86% probability of being cost effective compared with no screening.. Our analysis demonstrated that AMD screening carried out simultaneously with DR screening for patients with diabetes would be cost effective in a Hong Kong public healthcare setting.

Topics: Aged; Aged, 80 and over; Antioxidants; beta Carotene; Cost-Benefit Analysis; Diabetic Retinopathy; Diagnostic Techniques, Ophthalmological; Female; Health Care Costs; Hong Kong; Humans; Macular Degeneration; Male; Markov Chains; Mass Screening; Middle Aged; Photography; Quality-Adjusted Life Years; Sensitivity and Specificity; Visual Acuity; Zinc Compounds

Diabetic retinopathy increases with duration of diabetes and may be associated with carotenoid status. Carotenoids alter the pro-oxidation/antioxidation balance, and circulating levels depend largely on dietary intake. Lower levels have been reported in diabetes and age-related macular degeneration; however, little is known of the relationship between carotenoids and diabetic complications. Consequently, the purpose of the present study was to evaluate the relationship between plasma carotenoids and diabetic retinopathy. We assessed the carotenoid-retinopathy relationship in 111 individuals with type 2 diabetes in a community-based, cross-sectional study. We photodocumented retinal status and used HPLC to measure plasma carotenoid concentrations. Data for clinical and demographic variables and risk factors for diabetic retinopathy were obtained from 24 h urine and fasting blood samples, and an interviewer-assisted lifestyle questionnaire. We found that the combined lycopene and lutein/zeaxanthin (non-pro-vitamin A (non-PVA) carotenoid) concentration when compared with the pro-vitamin A (PVA) carotenoids (alpha-carotene, beta-carotene and beta-cryptoxanthin) was significantly lower in the retinopathy than non-retinopathy group (OR 1.2 (95% CI 1.0, 1.4) v. 1.6 (95% CI 1.4, 1.7), respectively; P=0.009). A higher non-PVA:PVA ratio also predicted a lower risk of diabetic retinopathy, after adjustment for potential confounders (OR 0.33 (95% CI 0.12, 0.95); P=0.039). Finally, a higher concentration of PVA carotenoids was associated with greater odds of diabetic retinopathy, after adjustment for risk factors (P=0.049). We suggest synergies between carotenoids are implicated in diabetic retinopathy, independent of established risk factors. Importantly, our observations indicate dietary modulation of retinopathy risk may be possible by increasing intakes of lutein- and lycopene-rich foods.

Topics: Adult; Aged; Antioxidants; beta Carotene; Biomarkers; Blood Glucose; Carotenoids; Chi-Square Distribution; Cross-Sectional Studies; Cryptoxanthins; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Lutein; Lycopene; Male; Middle Aged; Risk; Xanthophylls; Zeaxanthins

To investigate whether the micronutrients that were shown to reduce the risk of development of age-related macular degeneration in the Age-Related Eye Disease Study (AREDS) can have the same effect on the development of diabetic retinopathy in rats, and to understand the possible mechanisms.. Streptozotocin-induced diabetic rats received a powdered diet with or without supplemental micronutrients (ascorbic acid, vitamin E, beta-carotene, zinc, and copper). The retina was used after the rats had diabetes for 12 months to detect vascular histopathology and to measure the biochemical parameters and messenger RNA levels of the genes involved in oxidative and nitrative stress.. The AREDS-based micronutrients prevented a diabetes-induced increase in the number of retinal acellular capillaries. In the same rats, micronutrients inhibited increases in retinal oxidatively modified DNA and nitrotyrosine and decreases in manganese superoxide dismutase. Diabetes-induced alterations in the messenger RNA expression of mitochondrial electron transport complex III (coenzyme Q cytochrome-c reductase) and inducible nitric oxide synthase were also prevented.. Age-Related Eye Disease Study-based micronutrients inhibit the development of diabetic retinopathy in rodents by inhibiting oxidative and nitrative stress.. Micronutrients that slow down the onset and progression of age-related macular degeneration have the potential to inhibit the development of diabetic retinopathy.

Topics: Animals; Ascorbic Acid; beta Carotene; Body Weight; Copper; Deoxyadenosines; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Diet; Eating; Electron Transport Complex III; Glycated Hemoglobin; Immunoenzyme Techniques; Male; Micronutrients; Nitric Oxide Synthase Type II; Oxidative Stress; Polymerase Chain Reaction; Rats; Rats, Inbred Lew; Retinal Vessels; RNA, Messenger; Superoxide Dismutase; Tyrosine; Vitamin E; Zinc Oxide

Diabetes mellitus is characterized by hyperglycemia and, in chronic disease, by microvascular pathologies, especially in the kidney, peripheral nerve, and eye. Although hyperglycemia can be controlled with insulin and/or antihyperglycemic medications, diabetic retinopathy continues to be the leading cause of blindness in the United States. Because increased oxidative stress may be a cause of retinopathy, this study examined the hypothesis that administration of exogenous antioxidants can restore a more balanced oxidative condition. Normal and 30-day streptozotocin-induced diabetic Sprague-Dawley rats received daily intraperitoneal doses (10 mg/kg) of beta-carotene, alpha-lipoic, and Pycnogenol individually or in combinations for 14 days, after which retinae were dissected and fractionated for the assay of activities of glutathione reductase, glutathione peroxidase, gamma-glutamyl transferase, and superoxide dismutase. In normal rats, treatment with antioxidant combinations led to a decrease in gamma-glutamyl transferase activity; beta-carotene plus pycnogenol treatment decreased the activity of both glutathione-related enzymes. Decreased retinal gamma-glutamyl transferase activity of diabetic rats was normalized by the administration of pycnogenol alone or in combination with beta-carotene. In diabetic rats, retinal glutathione reductase activity increased after treatment with beta-carotene alone or with pycnogenol. Treatment with pycnogenol and alpha-lipoic acid alone or in combination decreased the activity of glutathione peroxidase, while this activity was increased after treatment with a combination of all antioxidants. Elevated activity of superoxide dismutase in diabetic retina was normalized by treatment with alpha-lipoic acid and with pycnogenol and beta-carotene in combination, but not with all three together. Antioxidants can access the retina and, once there, can alter antioxidant enzyme activities. In both normal and diabetic rats, combinations of antioxidants have different effects on retinal antioxidant enzyme activities than do individual antioxidants.

Topics: Animals; Antioxidants; beta Carotene; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Drug Combinations; Female; Flavonoids; gamma-Glutamyltransferase; Glutathione Peroxidase; Glutathione Reductase; Oxidative Stress; Oxidoreductases; Plant Extracts; Rats; Rats, Sprague-Dawley; Retina; Superoxide Dismutase; Thioctic Acid

Oxidative stress is increased in the retina in diabetes, and long-term administration of antioxidants inhibits the development of retinopathy in diabetic rats. The purpose of this study is to determine how diabetes affects the activation of a redox-sensitive nuclear transcriptional factor in the retina, NF-kappaB, and its inhibition by antioxidants. Alloxan diabetic rats were assigned to receive standard diet or the diet supplemented with multiple antioxidants, including ascorbic acid, Trolox, dl alpha-tocopherol acetate, N-acetyl cysteine, beta-carotene, and selenium for up to 14 months. NF-kappaB activation, oxidative stress and nitric oxides were measured in the retina at 2, 8 and 14 months of diabetes. Retinal NF-kappaB was activated by about 60% at two months after induction of diabetes, remained activated for up to 14 months of diabetes, and the duration of diabetes had no effect on the intensity of NF-kappaB activation. Similarly, oxidative stress and nitric oxides were elevated by over 50% in the retina of rats diabetic for 14 months, and nitrotyrosine levels were elevated by over two folds. Administration of the antioxidants to the rats for the entire duration of diabetes inhibited activation of NF-kappaB and elevations in oxidative stress, nitric oxides and nitrotyrosine formation without ameliorating the severity of hyperglycemia. These in vivo results were confirmed by in vitro studies showing that high glucose activates NF-kappaB and elevates NO and lipid peroxides in both retinal endothelial cells and pericytes that can be inhibited by antioxidants. Thus, the results suggest that the activation of retinal NF-KB in diabetes is an early event in the development of retinopathy, and it remains active when the retinal capillary cell death is accelerating, and histopathology is developing. Beneficial effects of antioxidants on the development of diabetic retinopathy might involve inhibition of NF-kappaB activation and its downstream pathways in the retina.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Chromans; Cysteine; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Glucose; Lipid Peroxides; Male; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Rats; Rats, Sprague-Dawley; Retina; Selenium; Tyrosine

Apoptosis of retinal endothelial cells and pericytes is postulated to contribute to the development of retinopathy in diabetes. The goal of this study is to investigate diabetes-induced activation of retinal caspase-3, an apoptosis executer enzyme, in retina, and examine the effects of antioxidants on the activation. Caspase-3 activation was determined in the retina of alloxan diabetic rats (2-14 months duration) and in the isolated retinal capillary cells (endothelial cells and pericytes) by measuring cleavage of caspase-3 specific fluorescent substrate, and cleavage of caspase-3 holoenzyme and poly (ADP ribosyl) polymerase. Effect of antioxidants on the activation of caspase-3 was determined by feeding a group of diabetic rats diet supplemented with a comprehensive mixture of antioxidants, including Trolox, alpha-tocopherol, N-acetyl cysteine, ascorbic acid, beta-carotene and selenium for 2-14 months, and also under in vitro conditions by incubating isolated retinal capillary cells with antioxidants with wide range of actions. Caspase-3 was activated in the rat retina at 14 months of diabetes (P < 0.05 vs. normal), but not at 2 months of diabetes, and administration of antioxidants for the entire duration inhibited this activation. In the isolated retinal capillary cells incubated in 25 mM glucose medium, caspase-3 activity was increased by 50% compared to the cells incubated in 5 mM glucose (P < 0.02), and antioxidants or caspase-3 inhibitor inhibited this increase. Our results suggest that increased oxidative stress in diabetes is involved in the activation of retinal caspase-3 and apoptosis of endothelial cells and pericytes. Antioxidants might be inhibiting the development of diabetic retinopathy by inhibiting microvascular apoptosis.

Topics: Acetylcysteine; alpha-Tocopherol; Animals; Antioxidants; Apoptosis; Ascorbic Acid; beta Carotene; Caspase 3; Caspases; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Endothelium, Vascular; Enzyme Activation; Glucose; In Vitro Techniques; Male; Oxidative Stress; Pericytes; Poly(ADP-ribose) Polymerases; Rats; Rats, Sprague-Dawley; Retina; Selenium; Thiobarbituric Acid Reactive Substances

Antioxidants were administered to diabetic rats and experimentally galactosemic rats to evaluate the ability of these agents to inhibit the development of diabetic retinopathy. Alloxan diabetic rats and nondiabetic rats that were fed 30% galactose randomly received standard diets or the diets supplemented with ascorbic acid and alpha-tocopherol (vitamins C+E diet) or a more comprehensive mixture of antioxidants (multi-antioxidant diet), including Trolox, alpha-tocopherol, N-acetyl cysteine, ascorbic acid, beta-carotene, and selenium. Diabetes or galactose feeding of at least 12 months resulted in pericyte loss, acellular capillaries, and basement membrane thickening. Compared with diabetic controls, the development of acellular capillaries was inhibited by 50% (P < 0.05) in diabetic rats that received supplemental vitamins C+E, and the number of pericyte ghosts tended to be reduced. The vitamins C+E supplement had no beneficial effect in galactosemic rats, but these rats consumed only approximately half as much of the antioxidants as the diabetic rats. The multi-antioxidant diet significantly inhibited ( approximately 55-65%) formation of both pericyte ghosts and acellular capillaries in diabetic rats and galactosemic rats (P < 0.05 vs. controls), without affecting the severity of hyperglycemia. Parameters of retinal oxidative stress, protein kinase C activity, and nitric oxides remained elevated for at least 1 year of hyperglycemia, and these abnormalities were normalized by multi-antioxidant therapy. Thus, long-term administration of antioxidants can inhibit the development of the early stages of diabetic retinopathy, and the mechanism by which this action occurs warrants further investigation. Supplementation with antioxidants can offer an achievable and inexpensive adjunct therapy to help inhibit the development of retinopathy in diabetes.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Chromans; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Diet; Dietary Supplements; Galactosemias; Male; Pericytes; Rats; Rats, Sprague-Dawley; Retina; Retinal Diseases; Selenium; Vitamin E

Diabetic retinopathy (DR) is a major cause of visual impairment and blindness in adults. Antioxidant nutrients, such as vitamins C and E and beta-carotene, may be protective of some eye disorders, such as cataract and age-related macular degeneration, but a relationship between these nutrients and DR has yet to be defined. The purpose of this study was to examine the relation between dietary and supplement intakes of vitamins C, E, and beta-carotene and the risk of DR.. Both cross-sectional and longitudinal data were collected from participants in the San Luis Valley Diabetes Study, including non-Hispanic white and Hispanic adults in southern Colorado.. A total of 387 participants with type 2 diabetes completed at least 1 complete retinal examination and 24-hour dietary recall (including vitamin supplement use).. Type 2 diabetes was defined according to World Health Organization criteria. DR was assessed by retinal photographs, using the Airlie House criteria to classify DR as none, background, preproliferative, or proliferative. Data for both eyes, from up to three clinic visits per participant, were used for analysis. Ordinal logistic regression analysis was used, taking advantage of multiple clinic visits by individual participants and observations from both eyes, to assess the risk for increased DR severity over time as a function of changes in intake of vitamin C, vitamin E, and beta-carotene. Six categories of intake for each nutrient (first to fourth quintiles and ninth and tenth deciles) were considered to ascertain any potential threshold effect. Analyses accounted for age, duration of diabetes, insulin use, ethnicity, glycated hemoglobin, hypertension, gender, and caloric intake.. An increase over time in vitamin C intake from the first to ninth deciles was associated with a risk for increased severity of DR (odds ratio = 2.21, P = 0.01), although excess risk was not observed for the tenth decile or the second through fourth quintiles compared to the first quintile. Increased intake of vitamin E was associated with increased severity of DR among those not taking insulin (odds ratios = 2.69, 2.59, 3.33, 5.65, 3.79; P < 0.02, for an increase over time from the first to the second through fourth quintiles and ninth and tenth deciles, respectively). Among those taking insulin, increased intake of beta-carotene was associated with a risk for severity of DR (odds ratio = 3.31, P = 0.003, and 2.99, P = 0.002, respectively, for the ninth and tenth deciles compared to the first quintile).. No protective effect was observed between antioxidant nutrients and DR. Depending on insulin use, there appeared to be a potential for deleterious effects of nutrient antioxidants. Further research is needed to confirm associations of nutrient antioxidant intake and DR.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; California; Colorado; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Dietary Supplements; Female; Humans; Insulin; Longitudinal Studies; Male; Middle Aged; Prevalence; Risk Factors; Vitamin E