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Query: UMLS:C0011849 (diabetes)
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Retinol and retinyl palmitate in the moderate doses tested in chemoprevention trials produce only a negligible increase in serum triglyceride levels. The effect is nonprogressive and is not associated with the kind of exaggerated response reported for interacting factors such as presence of diabetes mellitus and/or high baseline values for serum triglyceride concentration. These findings seem to represent an advantage for safety of retinol in relation to isotretinoin (13-cis-retinoic acid).
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PMID:Long-term vitamin A does not produce clinically significant hypertriglyceridemia: results from CARET, the beta-carotene and retinol efficacy trial. 788 45

In an in-depth examination to better define the renal effects of mild hypertension, we used urinary proteins to indicate damage to the glomerulus (albumin), tubular reabsorption capability (retinol-binding protein), and turnover of tubular tissue (alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase) in a group of 18 people with mild hypertension not associated with diabetes and a control group (n = 12). The participants' activity was controlled on a high normal salt diet for 3 days followed by a low salt diet for 4 days. Two distinct patterns of albumin excretion were evident in the hypertensive group: 22% had elevated, highly variable excretion patterns, and the rest had tightly grouped values below 16 mg/g creatinine, 16 micrograms/min, or 16 mg/L, with the lowest within-person biological variability given by albumin calculated as a ratio to creatinine. Albumin and NAG excretion primarily correlated with systolic blood pressure and the best correlations were given by ratios to creatinine. A marked decrease in salt excretion of 71% (to 50.8 mEq/day) resulted in significant (P < .0005) decreases in systolic (13.9 mm Hg), diastolic (6.4 mm Hg), and mean arterial pressures (8.9 mm Hg) only in the group with mild hypertension. However, albumin excretion did not decrease when dietary salt content was lowered. The group with hypertension also had higher urinary excretion of lysosomal N-acetyl-beta-D-glucosaminidase (P < .01), and whites in the group had a higher excretion of retinol-binding protein than did whites in the control group (P < .02). Retinol-binding protein values, however, were within the normal range, indicating that the elevated albumin values were the result of changes in selectivity of the glomerulus.
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PMID:An in-depth examination of the excretion of albumin and other sensitive markers of renal damage in mild hypertension. 855 30

The study was designed to evaluate whether the antioxidant nutrients selenium, vitamin A, and vitamin E are associated with alterations of blood viscosity in patients with insulin-dependent (Type 1) diabetes mellitus (IDDM). We assessed selenium concentrations in plasma and red blood cells (RBC), glutathione peroxidase activity in RBC, vitamin A and vitamin E, and the viscosity of whole blood and plasma in 20 patients with IDDM and 20 sex, age and body mass index-matched healthy controls. While selenium was not altered in plasma in IDDM, it was markedly decreased in RBC of IDDM (1.24 +/- 0.32 vs 0.92 +/- 0.38 mumol l-1, p = 0.006) correlating negatively with the elastic and viscous component of whole blood viscosity. Plasma viscosity increased with stage of retinopathy. Mean glutathione peroxidase activity in RBC was reduced in IDDM (5.78 +/- 0.77 vs 5.13 +/- 1.03 U gHb-1, p = 0.029). In IDDM with normal renal function (creatinine < or = 97.2 mumol l-1, no albuminuria) vitamin A was significantly reduced (1.26 +/- 0.62 vs 1.89 +/- 0.56 mumol l-1, p = 0.005). Vitamin A levels increased with impaired renal function. They strongly correlated with plasma creatinine (r = 0.86, p < 0.001) and plasma viscosity (r = 0.71, p = 0.001). However, in vitro experiments with different vitamin A plasma concentrations indicated that this particular correlation may not represent a causal one. No changes in vitamin E were found in IDDM. We conclude that reduced selenium concentrations in RBC contribute to impaired haemorheology in IDDM patients. Plasma viscosity was not affected by the plasma concentrations of vitamins A and E.
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PMID:Nutritional antioxidants, red cell membrane fluidity and blood viscosity in type 1 (insulin dependent) diabetes mellitus. 897 86

Retinol-binding protein (RBP) and transthyretin (TTR) in the plasma, liver and kidney, retinol in plasma, and total vitamin A in the liver were measured in rats 6 weeks after diabetes mellitus had been induced by streptozotocin (STZ). The diabetic rats gained 83% less weight despite consuming 45% more feed than the non-diabetic controls. Plasma and kidney concentrations of RBP and TTR were significantly lower in diabetic than in the non-diabetic control rats. Unlike the retinol carrier proteins, plasma albumin concentrations remained unaffected. Plasma concentrations of retinol were decreased while its hepatic levels increased in the diabetic animals. The depressed circulatory levels of retinol may reflect an altered metabolism of its transport proteins.
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PMID:Streptozotocin-induced diabetes lowers retinol-binding protein and transthyretin concentrations in rats. 901 57

The authors conducted a case-control study among the multi-ethnic population of Hawaii to examine the role of dietary soy, fiber, and related foods and nutrients on the risk of endometrial cancer. Endometrial cancer cases (n = 332) diagnosed between 1985 and 1993 were identified from the five main ethnic groups in the state (Japanese, Caucasian, Native Hawaiian, Filipino, and Chinese) through the rapid-reporting system of the Hawaii Tumor Registry. Population controls (n = 511) were selected randomly from lists of female Oahu residents and matched to cases on age (+/-2.5 years) and ethnicity. All subjects were interviewed using a diet history questionnaire that included over 250 food items. Non-dietary risk factors for endometrial cancer included nulliparity, never using oral contraceptives, fertility drug use, use of unopposed estrogens, a history of diabetes mellitus or hypertension, and a high Quetelet's index (kg/cm2). Energy intake from fat, but not from other sources, was positively associated with the risk of endometrial cancer. The authors also found a positive, monotonic relation of fat intake with the odds ratios for endometrial cancer after adjustment for energy intake. The consumption of fiber, but not starch, was inversely related to risk after adjustment for energy intake and other confounders. Similar inverse gradients in the odds ratios were obtained for crude fiber, non-starch polysaccharide, and dietary fiber. Sources of fiber, including cereal and vegetable and fruit fiber, were associated with a 29-46% reduction in risk for women in the highest quartiles of consumption. Vitamin A and possibly vitamin C, but not vitamin E, were also inversely associated with endometrial cancer, although trends were not strong. High consumption of soy products and other legumes was associated with a decreased risk of endometrial cancer (p for trend = 0.01; odds ratio = 0.46, 95% confidence interval 0.26-0.83) for the highest compared with the lowest quartile of soy intake. Similar reductions in risk were found for increased consumption of other sources of phytoestrogens such as whole grains, vegetables, fruits, and seaweeds. Ethnic-specific analyses were generally consistent with these results. The observed dietary associations appeared to be largely independent of other risk factors, although the effects of soy and legumes on risk were limited to women who were never pregnant or who had never used unopposed estrogens. These data suggest that plant-based diets low in calories from fat, high in fiber, and rich in legumes (especially soybeans), whole grain foods, vegetables, and fruits reduce the risk of endometrial cancer. These dietary associations may explain in part the reduced rates of uterine cancer in Asian countries compared with those in the United States.
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PMID:Association of soy and fiber consumption with the risk of endometrial cancer. 927 Apr 8

There are indications that beta-carotene, but not pre-formed vitamin A, is protective on the risk of acute myocardial infarction (AMI). The relationship between nonfatal AMI and the intake of beta-carotene and retinol was investigated in a case-control study conducted between 1983 and 1992 in northern Italy on 433 women with nonfatal AMI and 869 controls in hospital for acute, non-cardiovascular, non-neoplastic, non-digestive, non-hormone related conditions. Odds ratios (OR), with their 95% confidence intervals (CI), were computed by unconditional multiple logistic regression analysis, including terms for age, education, body mass index, smoking, alcohol and coffee drinking, menopausal status, hormone replacement therapy and history of diabetes, hypertension and hyperlipidemia. The risk of AMI was inversely related to beta-carotene intake, with an OR of 0.5 (95% CI: 0.3 to 0.8) for the highest quintile of intake compared to the lowest (chi2 trend = 10.53, p < 0.01). Retinol intake was not associated with AMI, with an OR of 0.9 (95% CI: 0.6 to 1.3) for the highest quintile of intake compared to the lowest. Analysis in separate strata of covariates indicated that the inverse association of beta-carotene intake with risk of AMI was appreciably stronger in younger, lean women with no history of diabetes or hypertension, and in current smokers. The results of this study indicate that the risk of nonfatal AMI in women is inversely related to intake of beta-carotene containing foods, but not foods containing retinol.
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PMID:Beta-carotene intake and risk of nonfatal acute myocardial infarction in women. 932 8

1. Patients with insulin-dependent diabetes mellitus are classified among the groups at risk for low vitamin status, and recent studies suggest that some degree of supplementation with antioxidants may be beneficial in helping to prevent certain long-term complications of diabetes mellitus. Our objective was to compare the status of the fat-soluble vitamins and antioxidant-related compounds in patients with well-defined insulin-dependent diabetes mellitus with that of their first-degree relatives, controlling seasonal and analytical variability as factors influencing the interpretation of the data. 2. Fifty-four patients with insulin-dependent diabetes mellitus, 214 non-diabetic, first-degree relatives (controls) and 236 unrelated controls were analysed for retinol, tocopherols (alpha and gamma) and main carotenoids in serum (beta-carotene, alpha-carotene, beta-cryptoxanthin, lutein, zeaxanthin and lycopene) by means of a validated HPLC method. 3. Insulin-dependent diabetes mellitus was associated with lower retinol levels and higher levels of beta-carotene, alpha-carotene and beta-cryptoxanthin than sex-matched, first-degree relatives. alpha-Tocopherol, the alpha-tocopherol/cholesterol ratio, gamma-tocopherol, lutein, zeaxanthin and lycopene showed no differences. Retinol and beta-carotene were the variables most closely associated with diabetes. 4. Patients with insulin-dependent diabetes mellitus showed lower serum retinol status together with higher concentrations of provitamin-A carotenoids. Serum fat-soluble antioxidant levels were greater than or equal to those in controls. According to the serum status observed, individuals with diabetes do not require supplementation with alpha-tocopherol or carotenoids, although the need for retinol supplementation in patients with marginal serum levels should be evaluated.
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PMID:Carotenoids, retinol and tocopherols in patients with insulin-dependent diabetes mellitus and their immediate relatives. 953 28

Naturally occurring retinoids (vitamin A or retinol and its active metabolites) are vital for vision, controlling the differentiation program of epithelial cells in the digestive tract and respiratory system, skin, bone, the nervous system, the immune system, and for hematopoiesis. Retinoids are essential for growth, reproduction (conception and embryonic development), and resistance to and recovery from infection. The functions of retinoids in the embryo begin soon after conception and continue throughout the lifespan of all vertebrates. Both naturally occurring and synthetic retinoids are used in the therapy of various skin diseases, especially acne, for augmenting the treatment of diabetes, and as cancer chemopreventive agents. Retinol metabolites serve as ligands that activate specific transcription factors in the superfamily of steroid/retinoid/thyroid/vitamin D/orphan receptors and thereby control gene expression. Additionally, retinoids may also function through non-genomic actions. Various retinoid binding proteins serve as partners in retinoid function. These binding proteins show high specificity and affinity for specific retinoids and seem to control retinoid metabolism in vivo qualitatively and quantitatively by reducing 'free' retinoid concentrations, protecting retinoids from non-specific interactions, and chaperoning access of metabolic enzymes to retinoids. Implementation of the physiological effects of retinoids depends on the spatial-temporal expressions of binding proteins, receptors and metabolic enzymes. This review will discuss current understanding of the enzymes that catalyze retinol and retinoic acid metabolism and their unique and integral relationship to retinoid binding proteins.
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PMID:Interactions of retinoid binding proteins and enzymes in retinoid metabolism. 1052 99

Diabetes mellitus is the most common genetic disease in the Western world today. It is the phenotype for >150 genotypes. Each of these genotypes is characterized by impaired glucose tolerance and impaired control of intermediary metabolism. There are many strains of mice and rats that can be used to study diabetes in its various forms. One of these is the BHE/Cdb rat, which mimics the human phenotype with a mutation in the mitochondrial (mt) DNA. The result of such mutation is a loss in metabolic control with respect to the role of the mitochondria in this control. This review addresses those aspects of control that are exerted by mt oxidative phosphorylation (OXPHOS). Diet can have both genomic and nongenomic effects on OXPHOS. The type of dietary fat influences the fluidity of the mt membranes and hence, mt function. The dietary fat effect depends on the genetic background of the consumer. Diabetes-prone BHE/Cdb rats with base substitutions in the mt ATPase 6 gene are more likely to be influenced by the diet effect on mt membrane fluidity than are normal rats. Vitamin A also affects mt function through an effect on mt gene expression. BHE/Cdb rats have a greater need for vitamin A than normal rats and supplemental vitamin A appears to influence OXPHOS.
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PMID:Diabetes and nutrition: the mitochondrial part. 1116 May 59

Diabetes-prone BHE/Cdb and Sprague-Dawley (SD) rats were studied with respect to mitochondrial (mt) function and mt gene expression. The BHE/Cdb rats carry mutations in the mt ATPase 6 gene that phenotype as decreased OXPHOS efficiency with subsequent development of impaired glucose tolerance. The base substitutions result in amino acid substitutions in the proton channel and this, in turn, affects the efficiency of energy capture in the ATP molecule. Feeding studies showed that BHE/Cdb rats required 10 times more vitamin E and three times more vitamin A in their diets than do normal SD rats. Vitamin A supplementation 'normalized' mt OXPHOS as well as increased the amount of ATPase subunit a protein in the mt compartment. Western blot analysis of retinoic acid receptors in the mitochondrial and nuclear compartments showed that these proteins were present in the mt compartment. The effect of the vitamin A supplementation plus the observation of retinoic acid receptors suggest that vitamin A functions to enhance the transcription of the ATPase 6 gene. Work with primary cultures of hepatocytes showed that not only does retinoic acid increase mitochondrial ATPase 6 gene expression but so too does the steroid hormone intermediate, dehydroepiandrosterone (DHEA). Triiodothyronine also plays a role in this process but not as an independent factor. Rather, this hormone potentiates the effects of retinoic acid and DHEA on ATPase gene expression. These results suggest that mt gene expression requires more than just the mt transcription factor A. More than likely the process requires a number of factors in much the same way as does nuclear gene expression.
Diabetes Res Clin Pract 2001 Dec
PMID:Role of vitamin A in mitochondrial gene expression. 1173 5


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