beta-carotene and Diabetes-Mellitus--Type-1

Diabetic patients are exposed to increased oxidative stress due to several mechanisms, mainly hyperglycaemia. Pathological processes, such as those in type 1 diabetes, include diminished activity of the antioxidant defense system(s) or excessive oxidative generation resulting in an oxidative/antioxidant imbalance and development of oxidative stress.. The purpose of this study was to evaluate the production of reactive oxygen species (ROS) (chemiluminescence) and reduction capacity (MTT dye reduction), the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, superoxide dismutase and catalase using quantitative reverse-transcriptase polymerase chain reaction, and the levels of cytokines [interleukin (IL)-6, tumour necrosis factor-α, IL-8, IL-10 and IL-4] by sandwich enzyme-linked immunosorbent assay in mononuclear cells from non-diabetic and diabetic donors treated with a vitamin complex (ascorbic acid, β-carotene and α-tocopherol) in two different concentrations ([A] = ascorbic acid = 0.08 µM, α-tocopherol = 0.04 µM, β-carotene = 0.0008 µM and [20A] = ascorbic acid = 1.6 µM, α-tocopherol = 0.82 µM, β-carotene = 0.016 µM).. Concentration [A] was antioxidant reducing ROS production, expression of NADPH oxidase subunits and pro-inflammatory cytokines while raising the expression of antioxidant enzymes and reducing pro-inflammatory cytokines in both groups. Concentration [20A] was pro-oxidant by raising ROS production, NADPH oxidase subunits and pro-inflammatory cytokines and reducing antioxidant enzymes and anti-inflammatory cytokines in the non-diabetic group but antioxidant in cells of type 1 diabetic patients by raising antioxidant enzymes and anti-inflammatory cytokines and reducing pro-inflammatory cytokines.. The vitamin complex has a dual effect, pro-oxidant and antioxidant, being also dose dependent with different profiles of cells of non-diabetic and type 1 diabetic patients.

Topics: Adult; Aged; Aged, 80 and over; alpha-Tocopherol; Ascorbic Acid; beta Carotene; Catalase; Cytokines; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Gene Expression Regulation; Humans; Leukocytes, Mononuclear; Middle Aged; NADPH Oxidases; Oxidative Stress; Reactive Oxygen Species; Superoxide Dismutase

Reactive oxygen intermediates have been implicated in mediating the destruction of insulin-producing beta cells and antioxidant nutrients thought to protect against such a process. This study aimed to assess the associations between serum α- and β-carotene concentrations, and the risk of advanced beta-cell autoimmunity, in children with HLA-conferred susceptibility to type 1 diabetes.. This case-control study, comprising 108 case children with advanced beta-cell autoimmunity and 216 matched control children, was nested within the nutrition study of the Type 1 Diabetes Prediction and Prevention (DIPP) birth cohort. Serum α- and β-carotene samples were collected each year from the age of 1 to 6 years. For each case-control group, serum samples were analyzed up to the time of seroconversion in the case children. Associations were studied using a conditional logistic-regression model.. Neither serum α- nor β-carotene concentration was significantly associated with the risk of advanced beta-cell autoimmunity. There was marginal evidence (P=0.049) of an inverse association between serum β-carotene concentration and the risk of developing advanced beta-cell autoimmunity at a time closest to seroconversion after adjusting for parental education, maternal age, duration of gestation, diabetes in first-degree relatives, number of earlier deliveries and maternal smoking during pregnancy.. The present study data provided no clear evidence to support an association between serum α- or β-carotene concentration and advanced beta-cell autoimmunity.

Topics: Autoimmunity; beta Carotene; Carotenoids; Case-Control Studies; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Genetic Predisposition to Disease; HLA Antigens; Humans; Infant; Insulin-Secreting Cells; Pregnancy

Increased oxidative stress and immune dysfunction are implicated in preeclampsia (PE) and may contribute to the two- to fourfold increase in PE prevalence among women with type 1 diabetes. Prospective measures of fat-soluble vitamins in diabetic pregnancy are therefore of interest.. Maternal serum carotenoids (α- and β-carotene, lycopene, and lutein) and vitamins A, D, and E (α- and γ-tocopherols) were measured at first (12.2 ± 1.9 weeks [mean ± SD], visit 1), second (21.6 ± 1.5 weeks, visit 2), and third (31.5 ± 1.7 weeks, visit 3) trimesters of pregnancy in 23 women with type 1 diabetes who subsequently developed PE (DM PE+) and 24 women with type 1 diabetes, matched for age, diabetes duration, HbA(1c), and parity, who did not develop PE (DM PE-). Data were analyzed without and with adjustment for baseline differences in BMI, HDL cholesterol, and prandial status.. In unadjusted analysis, in DM PE+ versus DM PE-, α-carotene and β-carotene were 45 and 53% lower, respectively, at visit 3 (P < 0.05), before PE onset. In adjusted analyses, the difference in β-carotene at visit 3 remained significant. Most participants were vitamin D deficient (<20 ng/mL), and vitamin D levels were lower in DM PE+ versus DM PE- throughout the pregnancy, although this did not reach statistical significance.. In pregnant women with type 1 diabetes, low serum α- and β-carotene were associated with subsequent development of PE, and vitamin D deficiency may also be implicated.

Topics: beta Carotene; Carotenoids; Diabetes Mellitus, Type 1; Female; Humans; Longitudinal Studies; Lycopene; Pre-Eclampsia; Pregnancy; Pregnancy in Diabetics; Vitamin A; Vitamin D

Type 1 diabetes (T1D) mellitus and obesity are recognized risk factors for cardiovascular disease (CVD). A common mechanism underlying an increased risk for endothelial dysfunction in these two metabolic diseases is oxidative stress.. To evaluate and compare the oxidant/antioxidant defense systems in children affected with T1D or obesity in order to determine the importance of oxidative stress before the emergence of complications.. Children with T1D (n = 20) or obesity (n = 22), without comorbidities, and age- and sex-matched controls (n = 16).. We assessed lipid peroxidation by circulating levels of lipoperoxides and malondialdehyde, as well as protein oxidation by the concentration of plasma carbonyl groups. The endogenous antioxidative defense system was evaluated by the red cell glutathione peroxidase and reduced glutathione. The serum levels of alpha-tocopherol and beta-carotene were determined to assess exogenous antioxidants.. Lipid peroxidation was significantly higher in both T1D and obese children when compared with control children. However, T1D patients showed a more elevated level, because their malondialdehyde values were significantly increased with respect to obese children. Protein oxidation was present in both groups of children and did not differ between them. With respect to obese children, the glutathione peroxidase activity and exogenous antioxidants were decreased in T1D patients.. Oxidative stress is present in both children with T1D and obesity, although it is more pronounced in the former. Obese children may suffer an additional oxidative stress in the case of developing impaired glucose metabolism.

Topics: Adolescent; alpha-Tocopherol; beta Carotene; Child; Diabetes Mellitus, Type 1; Erythrocytes; Female; Glutathione; Glutathione Peroxidase; Humans; Lipid Peroxidation; Lipid Peroxides; Male; Malondialdehyde; Obesity; Oxidative Stress; Prospective Studies; Protein Carbonylation; Retrospective Studies

Diabetic nephropathy (DN), a major cause of morbidity and mortality in diabetes, will develop within a subset of type 1 diabetes mellitus (T1DM) patients, and oxidative stress has been implicated in its pathogenesis. To investigate the relationship between indicators of early DN stages (hyperfiltration estimated by creatinine clearance > or =150 ml/min per 1.73 m(2), microalbuminuria) and oxidative stress, a prospective study was conducted in 29 T1DM patients (age 13.89 +/- 4.61 years) and 18 control subjects (age 13.23 +/- 3.99 years). Blood samples were collected to assay for biomarkers of oxidative stress (malondialdehyde and carbonyl groups) and antioxidants (glutathione peroxidase, reduced glutathione, alpha-tocopherol, and beta-carotene). With respect to control subjects, in T1DM patients, an increase was found in biomarkers of oxidative stress (p < 0.05), mainly due to the group of subjects with hyperfiltration, and a decrease in the ratio alpha-tocopherol/lipids (p < 0.05). In multiple regression analyses, age at disease onset, glycated hemoglobin, microalbuminuria, and oxidative stress biomarkers remained as explicative variables of hyperfiltration (R (2) adjusted = 0.731, p = 0.000). These findings support the importance of the oxidative damage to lipids and proteins, which is linked to hyperfiltration and which could contribute to the development of DN in patients with T1DM.

Topics: Adolescent; Age of Onset; Albuminuria; alpha-Tocopherol; Antioxidants; beta Carotene; Biomarkers; Child; Child, Preschool; Creatinine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Glomerular Filtration Rate; Glutathione; Glutathione Peroxidase; Humans; Male; Malondialdehyde; Oxidants; Oxidative Stress; Prospective Studies; Young Adult

Type-1 diabetics have been considered to be at risk for increased oxidative stress which has been implicated in the development of long-term diabetes complications. Evidence suggests that antioxidant activity may be an important mechanism by which carotenoids could confer protection in human health. Our aim was to compare the serum carotenoid depletion rate in type-1 diabetics and control subjects consuming low-carotenoid diets.. Ten type-1 diabetics and 8 controls followed a very low-carotenoid diet for 21 days. Dietary intake was recorded daily and fasting blood samples collected at baseline and after 1, 2, 3, 6, 11, 15, 16, 17, and 21 days. Individual carotenoids in serum were analyzed by a validated HPLC method.. In both groups, carotenoid intake was less than 5% of the season-adjusted carotenoid reference intake. These diets resulted in decreased serum carotenoid levels in both groups, although depletion curves, final mean concentrations and the estimated half-life of carotenoids in serum revealed no differences between type-1 diabetics and controls. Levels of other minor serum carotenoids, cis-isomers and keto-carotenoids, also decreased whereas serum retinol and alpha- and gamma-tocopherol did not change during the study.. Upon a low-carotenoid intake, the depletion rate of carotenoids in serum in young type-1 diabetics does not differ from that observed in matched related controls.

Topics: Adult; Antioxidants; beta Carotene; Carotenoids; Chromatography, High Pressure Liquid; Cryptoxanthins; Diabetes Mellitus, Type 1; Diet; Fasting; Female; Humans; Lycopene; Male; Xanthophylls

The aims of the study were to ascertain the potential role of oxidative stress in the onset of disease-related pathophysiological complications in young type 1 diabetes patients. Indicative parameters of lipoperoxidation, protein oxidation, and changes in antioxidant defense system status were measured in blood samples from 26 young diabetic patients with recently diagnosed (< 6 months) microangiopathy (+DC), 28 diabetic patients without complications (-DC), and 40 healthy age-matched controls (CR). Both diabetic groups presented similar fructosamine and glycated hemoglobin (HbA1c) values. Results showed erythrocyte glutathione peroxidase activity, glutathione content, and plasma beta-carotene to be significantly lower in diabetic patients compared with control subjects, but with no significant differences between -DC and +DC groups. Antioxidant enzyme superoxide dismutase activity was significantly higher in the erythrocytes of diabetic patients independently of the presence of microvascular complications. However, the plasma alpha-tocopherol/total lipids ratio was significantly diminished in +DC group compared with -DC (p =.008). Lipid peroxidation indices measured in plasma included malondialdehyde, lipid hydroperoxides, and lipoperoxides, which were significantly elevated in our diabetic patients regardless of the presence of complications. Evidence of oxidative damage to proteins was shown both through the quantification of plasma protein carbonyl levels, which were significantly higher in -DC (0.61 +/- 0.09 mmol/mg prot), and higher still in the +DC patients (0.75 +/- 0.09 mmol/mg prot) compared with those of controls (0.32 +/- 0.03 mmol/mg prot; p <.01) and immunoblot analysis of protein-bound carbonyls. Additionally, a marked increase in protein oxidation was observed in +DC patients through assessment of advanced oxidation protein products (AOPP) considered to be an oxidized albumin index; AOPP values were significantly higher in +DC than in -DC patients (p <.01) and CR (p <.0001). These results point to oxidatively modified proteins as a differential factor possibly related to the pathogenesis of diabetic complications.

Topics: Adolescent; Adult; alpha-Tocopherol; Antioxidants; beta Carotene; Biomarkers; Blood Proteins; Case-Control Studies; Diabetes Mellitus, Type 1; Erythrocytes; Female; Glutathione; Glutathione Peroxidase; Glycated Hemoglobin; Humans; Lipid Metabolism; Lipid Peroxidation; Male; Malondialdehyde; Oxidation-Reduction; Oxidative Stress; Superoxide Dismutase

Plasma beta-carotene, alpha-tocopherol and retinol were measured in 15 female and 5 male children with insulin-dependent diabetes mellitus (IDDM), and the correlations with plasma hemoglobin A1c (HbA1c) and fructosamine were analyzed. Twelve female and 8 male children served as age-matched controls. The plasma beta-carotene and alpha-tocopherol levels of the IDDM children were significantly higher than those of the control children, but there were no differences in plasma retinol or total lipid levels. The plasma beta-carotene level, beta-carotene/retinol ratio and beta-carotene/total lipids ratio each showed significant correlations with serum HbA1c and fructosamine in all subjects studied. Similarly, the plasma alpha-tocopherol level and alpha-tocopherol/total lipids ratio were correlated with these indexes of glycemic control. These findings suggest certain mechanisms may exist to prevent lipid peroxidation and vascular complications in IDDM patients.

Topics: Adolescent; beta Carotene; Blood Glucose; Child; Diabetes Mellitus, Type 1; Female; Fructosamine; Glycated Hemoglobin; Humans; Lipids; Male; Vitamin A; 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

To establish reference ranges for use in clinical and epidemiological studies, we determined concentrations of retinol, alpha-tocopherol, beta-carotene, alpha-carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene in 450 Spanish control subjects and 123 Spanish patients with insulin-dependent diabetes mellitus (IDDM). Results were grouped according to sex, and samples were collected throughout the year. Concentrations of retinol were significantly lower and beta-carotene and alpha-carotene were higher in women than in men, both in controls and IDDM subjects, whereas beta-cryptoxanthin concentrations were higher only in control women. Conditional logistic regression analysis showed that retinol, beta-carotene, and lycopene were the variables associated with diabetes. In comparison with other populations, our controls showed, in general, ordinary concentrations of retinol, comparatively low beta-carotene and high beta-cryptoxanthin concentrations, and a relatively high alpha-tocopherol/ cholesterol ratio.

Topics: Adolescent; Adult; Aged; Antioxidants; beta Carotene; Carotenoids; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Humans; Lutein; Male; Middle Aged; Reference Values; Regression Analysis; Sex Factors; Spain; Vitamin A; Vitamin E; Xanthophylls; Zeaxanthins

Pregnancy in insulin-dependent diabetes mellitus is associated with a greater incidence of fetal abnormality. Animal studies suggest that increased free-radical production and antioxidant depletion may contribute to this risk. The aim of the present study was, therefore, to assess nutritional antioxidant status and lipid peroxidation in diabetic mothers in comparison with a control group. A 7 d dietary history and a food-frequency questionnaire were performed and venous blood collected for biochemical analyses from thirty-eight diabetic mothers and matched control subjects before 12 weeks gestation. Protein intake was significantly greater in diabetic patients (81.4 (SE 14.8) v. 72.7 (SE 15.8) g/d, P = 0.015), while total sugar intake was less (79.5 (SE 13.2) v. 104.8 (SE 28.8) g/d, P < 0.001). There were no significant differences in the intake of the major antioxidant vitamins (retinol, vitamin C or vitamin E) or beta-carotene. However, intakes of a number of other micronutrients (including Se, Zn, Mg, Mn, riboflavin, thiamin, niacin and folate) were greater in diabetic patients. Among the nutritional chain-breaking antioxidants, serum levels of alpha-tocopherol (21.6 (SE 5.7) v. 17.3 (SE 4.7) mumol/, P = 0.0013), beta-carotene (0.27 (SE 0.18) v. 0.14 (SE 0.11) mumol/l, P = 0.003) and lycopene (0.23 (SE 0.17) v. 0.16 (SE 0.13) mumol/l, P = 0.03) were greater in diabetic patients. There was no evidence of greater lipid peroxidation in diabetic patients, and total antioxidant capacity was similar in the two groups. Overall, these results indicate that nutritional antioxidant status is better in this group of diabetic mothers than in control pregnant non-diabetic subjects attending the same maternity hospital.

Topics: Adult; Anticarcinogenic Agents; Antioxidants; beta Carotene; Carotenoids; Diabetes Mellitus, Type 1; Diet; Female; Humans; Lipid Peroxidation; Lycopene; Micronutrients; Nutritional Status; Pregnancy; Pregnancy in Diabetics; Vitamin E

We aimed to examine the relationship of serum lipids, lipoproteins, apolipoproteins and antioxidants with renal dysfunction as measured by urinary excretion of albumin and of retinol binding protein (RBP) in insulin-dependent diabetes mellitus (IDDM). We studied 121 patients with IDDM. Glomerular function was assessed as the urinary albumin/creatinine ratio (UA/UC), and tubular function as the urinary retinol-binding protein/creatinine ratio (UR/UC), both measured in three early morning spot urine samples. The mean (range) UA/UC was 1.95 mg/mmol (0.3-476.5) and UR/UC was 17.5 micrograms/mmol (1.0-1853.8). 17% of the patients had a UA/UC > 3 mg/mmol and 33% had a UR/UC > 20 micrograms/mmol. Significant positive correlations were observed between both UA/UC and UR/UC and the following: serum total cholesterol (P < 0.005); triglycerides (P < 0.001); apolipoproteins A-I (P < 0.05), A-II (P < 0.02) and B (P < 0.002); glycated haemoglobin (P < 0.002). No significant associations were found with serum vitamin E, beta-carotene or total antioxidant activity. In multiple regression, only UA/UC was independently associated with serum apo B and cholesterol concentrations. In conclusion, in IDDM glomerular dysfunction, as measured by UA/UC, is associated with elevated serum cholesterol, triglycerides, apo B, apo A-I and apo A-II, but not with HDL cholesterol or antioxidant status. Tubular dysfunction tends to occur with increasing albuminuria, but it is not independently associated with serum lipid, lipoprotein, apolipoprotein or antioxidant levels.

Topics: Adult; Aged; Albuminuria; Antioxidants; Apolipoprotein A-I; Apolipoprotein A-II; Apolipoproteins B; beta Carotene; Biomarkers; Blood Pressure; Cholesterol; Cholesterol, HDL; Creatinine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Glycated Hemoglobin; Humans; Kidney Glomerulus; Kidney Tubules; Lipoprotein(a); Lipoproteins; Male; Middle Aged; Regression Analysis; Retinol-Binding Proteins; Triglycerides; Vitamin E