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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid, on the dysfunction of the endothelium and smooth muscle cells in male WBN/Kob rats, a model of spontaneous diabetes mellitus. After oral 8-month treatment with EPA-E, the agent significantly and dose-dependently increased the migration activity of vascular endothelial cells and also decreased 5-bromodeoxyuridine (BrdU) uptake by vascular smooth muscle cells at a dose of 0.1 g/kg or higher. In addition, there were significant correlations between the endothelial cell migration or smooth muscle cell proliferation and the 4-hour fasting glucose level. These findings suggest that EPA-E has a suppressive effect on thrombosis and atherosclerosis.
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PMID:Long-term administration of highly purified eicosapentaenoic acid ethyl ester improves the dysfunction of vascular endothelial and smooth muscle cells in male WBN/Kob rats. 1114 21

Atherosclerosis is a major complication of type 2 diabetes. The pathogenesis of this complication is poorly understood, but it clearly involves production in the vascular wall of macrophage (Mo) lipoprotein lipase (LPL). Mo LPL is increased in human diabetes. Peripheral factors dysregulated in diabetes, including glucose and free fatty acids (FAs), may contribute to this alteration. We previously reported that high glucose stimulates LPL production in both J774 murine and human Mo. In the present study, we evaluated the direct effect of FAs on murine Mo LPL expression and examined the involvement of peroxisome proliferator-activated receptors (PPARs) in this effect. J774 Mo were cultured for 24 h with 0.2 mmol/l unsaturated FAs (arachidonic [AA], eicosapentaenoic [EPA], and linoleic acids [LA]) and monounsaturated (oleic acid [OA]) and saturated FAs (palmitic acid [PA] and stearic acid [SA]) bound to 2% bovine serum albumin. At the end of this incubation period, Mo LPL mRNA expression, immunoreactive mass, activity, and synthetic rate were measured. Incubation of J774 cells with LA, PA, and SA significantly increased Mo LPL mRNA expression. In contrast, exposure of these cells to AA and EPA dramatically decreased this parameter. All FAs, with the exception of EPA and OA, increased extra- and intracellular LPL immunoreactive mass and activity. Intracellular LPL mass and activity paralleled extracellular LPL mass and activity in all FA-treated cells. In Mo exposed to AA, LA, and PA, an increase in Mo LPL synthetic rate was observed. To evaluate the role of PPARs in the modulatory effect of FAs on Mo LPL gene expression, DNA binding assays were performed. Results of these experiments demonstrate an enhanced binding of nuclear proteins extracted from all FA-treated Mo to the peroxisome proliferator-response element (PPRE) consensus sequence of the LPL promoter. PA-, SA-, and OA-stimulated binding activity was effectively diminished by immunoprecipitation of the nuclear proteins with anti-PPAR-alpha antibodies. In contrast, anti-PPAR-gamma antibodies only significantly decreased AA-induced binding activity. Overall, these results provide the first evidence for a direct regulatory effect of FAs on Mo LPL and suggest a potential role of PPARs in the regulation of Mo LPL gene expression by FAs.
Diabetes 2001 Mar
PMID:Direct regulatory effect of fatty acids on macrophage lipoprotein lipase: potential role of PPARs. 1124 88

We report a 67-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), successfully treated with eicosapentaenoic acid ethyl ester (EPA-E) for about eight months. He showed bilateral auditory disturbance and slowly progressive gait ataxia at age 50 during treatment of diabetes mellitus (DM) with subcutaneous injection of insulin since age 29. At age 58 he manifested an acute hemiparesis of right extremities for one week with no abnormal findings on neuroradiological examinations. A permanent pacemaker was implanted at age 61 to treat frequent syncopal attacks due to complete atrioventricular block. On admission to our hospital, neurological examinations revealed dementia, auditory disturbance, severe cerebellar ataxia and mild atrophy of proximal muscles with systemic hyporeflexia. Based on a point mutation in position 3243 of mitochondrial DNA, he was diagnosed as having MELAS with severe DM, auditory disturbance and cardiac conduction block. After initiation of treatment with EPA-E at a dose of 2,700 mg/day he showed temporarily an improvement in auditory disturbance, blood glucose control and cerebellar ataxia. In objective evaluations for cerebellar ataxia, we could find significant decreases in times for 20 m walking and heel-knee patting in the ninth month, and in time for tracing of a whirl from the third to the ninth month, compared with those before treatment of EPA-E (p < 0.0001). Because EPA-E is taken into mitochondrial membranes and activates electron transmission enzyme complexes, it might be a candidate for therapy of mitochondrial encephalomyopathy, including MELAS.
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PMID:[A case of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), showing temporary improvement during the treatment with eicosapentaenoic acid ethyl ester]. 1199 86

n-3 FA are beneficial for cardiovascular health, reducing platelet aggregation, TG levels, and the risk of sudden death from myocardial infarction. The percentage of EPA + DHA in red blood cells (RBC), also known as the Omega-3 Index, has recently been proposed as a risk marker for death from coronary heart disease (CHD). The purpose of this study was to begin to explore the factors that can influence RBC EPA + DHA. We collected information on the number of servings of tuna or nonfried fish consumed per month, as well as on age, gender, ethnicity, smoking status, the presence of diabetes, and body mass index (BMI) in 163 adults in Kansas City who were not taking fish oil supplements. The average RBC EPA + DHA in this population was 4.9 +/- 2.1%. On a multivariate analysis, four factors significantly and independently influenced the Omega-3 Index: fish servings, age, BMI, and diabetes. The Index increased by 0.24 units with each additional monthly serving of tuna or nonfried fish (P < 0.0001), and by 0.5 units for each additional decade in age (P < 0.0001). The Index was 1.13% units lower in subjects with diabetes (P = 0.015) and decreased by 0.3% units with each 3-unit increase in BMI (P = 0.001). Gender or smoking status had no effect, and the univariate relationship with ethnicity vanished after controlling for fish intake. Given the importance of n-3 FA in influencing risk for death from CHD, further studies are warranted to delineate the nondietary factors that influence RBC EPA + DHA content.
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PMID:The impact of age, body mass index, and fish intake on the EPA and DHA content of human erythrocytes. 1602 15

Consumption of fish rich in n-3 highly unsaturated FAs (i.e., EPA and DHA) has been suggested to decrease the risk of lifestyle-related diseases such as coronary heart disease, cancer, diabetes, and dementia. Blood levels of those FA are known appropriate biomarkers of both the corresponding dietary FA intakes and fish consumption. In place of traditional handwork methods for extracting FA, we performed an accelerated solvent extraction (ASE) for at least 13 selected FA in plasma and erythrocytes to measure them by GLC. The FA levels (concentrations and compositions) in 35-50 microL of plasma or erythrocytes were extracted by ASE and measured by GLC. Intra- and interassay coefficients of variation were < or = 6.0% for both blood materials, except with a minor group of FA (< or = 1.0% of total FA). When ASE was compared with two traditional handwork methods, FA levels in plasma from 18 healthy subjects were all coincident with very high Pearson's correlation coefficients for the three sets of the same 18 samples (r > or = 0.85 to 0.95, P < 0.0001), except for 18:0 (r = 0.59, P < 0.01). Using ASE and GLC, we have developed a new method for determination the levels of FA in plasma and erythrocytes as biomarkers for dietary intake of fish, fat, and FA. This new method makes it feasible to measure small volumes of samples, automatically, quantitatively, routinely, easily, rapidly and cheaply, with acceptable precision and accuracy.
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PMID:Accelerated solvent extraction for quantitative measurement of fatty acids in plasma and erythrocytes. 1698 38

The literature reports strong correlations between UV exposure and latitude gradients of diseases. Evidence is emerging about the protective effects of UV exposure for cancer (breast, colo-rectal, prostate), autoimmune diseases (multiple sclerosis, type II diabetes) and even mental disorders, such as schizophrenia. For the first time, the available levels of vitamin D producing UV or "vitamin D UV" (determined from the previtamin D action spectrum) and erythemal (sunburning) UV from throughout the USA are measured and compared, using measurements from seven locations in the USA are measured and compared, using measurements from seven locations in the US EPA's high accuracy Brewer Spectrophotometer network. The data contest longstanding beliefs on the location-dependence and latitude gradients of vitamin D UV. During eight months of the year centered around summer (March-October), for all sites (from 18 degrees N to 44 degrees N latitude) the level of vitamin D UV relative to erythemal UV was equal (within the 95% confidence interval of the mean level). Therefore, there was no measured latitude gradient of vitamin D UV during the majority of the year across the USA. During the four cooler months (November-February), latitude strongly determines vitamin D UV. As latitude increases, the amount of vitamin D UV decreases dramatically, which may inhibit vitamin D synthesis in humans. Therefore, a larger dose of UV relative to erythemal UV is required to produce the same amount of vitamin D in a high latitude location. However, the data shows that at lower latitude locations (<25 degrees N), wintertime vitamin D UV levels are equal to summertime levels, and the message of increasing UV exposure during winter is irrelevant and may lead to excessive exposure. All results were confirmed by computer modeling, which was also used to generalize the conclusions for latitudes from 0 degrees to 70 degrees N. The results of this paper will impact on research into latitudinal gradients of diseases. In particular, it may no longer be correct to assume vitamin D levels in populations follow significant latitude gradients for a large proportion of the year.
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PMID:Location and vitamin D synthesis: is the hypothesis validated by geophysical data? 1714 54

We tested the hypothesis that lower blood omega-3 (omega-3) fatty acids (FAs) and/or higher trans FAs are associated with the risk of an acute coronary syndrome (ACS). Higher levels of omega-3 FA have been associated with decreased risk of sudden cardiac death. However, their association with ACS risk is unclear. Although higher self-reported intakes of trans FAs have been linked to increased coronary risk, the association between blood levels of trans FA and ACS risk is also unknown. We analyzed the FA composition of whole blood from 94 subjects with ACS and 94 age-, gender-, and race-matched controls. Omega-3 and trans FA associations with ACS were assessed using multivariable models after adjusting for smoking status, alcohol use, diabetes, body mass index, serum lipids, and history of myocardial infarction or revascularization. Subjects' mean age was 47 years, 54% were men, and 80% were Caucasian. Whole blood long-chain omega-3 FA (eicosapentaenoic acid [EPA] plus docosahexaenoic acid [DHA]) content was 29% lower in patients than in controls (1.7 +/- 0.9% vs 2.4 +/- 1.4%, p <0.001), whereas trans FA content was not different (2.1 +/- 0.7% vs 2.0 +/- 0.9%, p = NS). The multivariable-adjusted odds for case status was 0.67 (95% confidence interval 0.46 to 0.98) for a 1 SD increase in blood EPA + DHA. The inclusion of trans FAs in the EPA + DHA model did not alter this association. In conclusion, low blood EPA + DHA content is an independent predictor of increased risk for ACS, but higher blood trans FA content is not. Blood EPA + DHA may serve as a new, modifiable risk factor for ACS.
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PMID:Blood omega-3 and trans fatty acids in middle-aged acute coronary syndrome patients. 1722 10

The human metabolic syndrome and its frequent sequela, type 2 diabetes are epidemic around the world. Alpha-linolenic acid (ALA, 18:3 n-3), eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) consumption ameliorates some of these epidemics' features thus leading one to question if consumption of EPA and DHA, and their metabolic precursor ALA reduce the conversion of metabolic syndrome to type 2 diabetes and reduce the major cause of death in the metabolic syndrome and type 2 diabetes-myocardial infarction. Contributing to myocardial infarction are metabolic syndrome's features of dyslipidemia (including elevated total cholesterol and LDL-c), oxidation, inflammation, hypertension, glucose intolerance, overweight and obesity. Inflammation, glucose and lipid levels are variously influenced by disturbances in various adipocytokines which are in turn positively impacted by n-3 polyunsaturated fatty acid consumption. Type 2 diabetes has all these features though elevated total cholesterol and LDL-c are rarer. It is concluded that EPA and DHA consumption significantly benefits metabolic syndrome and type 2 diabetes primarily in terms of dyslipidemia (particularly hypertriglyceridemia) and platelet aggregation with their impact on blood pressure, glucose control, inflammation and oxidation being less established. There is some evidence that EPA and/or DHA consumption, but no published evidence that ALA reduces conversion of metabolic syndrome to type 2 diabetes and reduces death rates due to metabolic syndrome and type 2 diabetes. ALA's only published significance appears to be platelet aggregation reduction in type 2 diabetes.
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PMID:The role of consumption of alpha-linolenic, eicosapentaenoic and docosahexaenoic acids in human metabolic syndrome and type 2 diabetes--a mini-review. 1789 98

The link between endocrine disruptors and altered blood glucose homeostasis has been recently suggested. Epidemiological studies have correlated levels of phthalates, dioxins and persistent organic pollutants with alterations of blood glucose homeostasis in humans. Environmentally relevant doses of the ubiquitous endocrine disruptor bisphenol-A (BPA) have profound effects on mice endocrine pancreas--an essential tissue involved in glucose metabolism. BPA exerts rapid non-genomic effects on insulin releasing beta-cells and glucagon releasing alpha-cells within freshly isolated islets of Langerhans. In vivo, a single BPA injection of 10 microg/kg rapidly increases plasma insulin and concomitantly decreases glycaemia. When mice were treated with BPA 100 microg/kg/day for 4 days, the environmental oestrogen produced an increase in beta-cell insulin content along with a post-prandial hyperinsulinaemia and insulin resistance. The results reviewed here demonstrate that doses well below the current lowest observed adverse effect level considered by the US-EPA, disrupt pancreatic beta-cell function producing insulin resistance in male mice. Therefore, this altered blood glucose homeostasis by BPA exposure may enhance the risk of developing type II diabetes.
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PMID:Bisphenol-A disruption of the endocrine pancreas and blood glucose homeostasis. 1797 Nov 60

Long-chain EPA/DHA omega-3 fatty acid supplementation can be co-preventative and co-therapeutic. Current research suggests increasing accumulated long chain omega-3s for health benefits and as natural medicine in several major diseases. But many believe plant omega-3 sources are nutritionally and therapeutically equivalent to the EPA/DHA omega-3 in fish oil. Although healthy, precursor ALA bio-conversion to EPA is inefficient and production of DHA is nearly absent, limiting the protective value of ALA supplementation from flax-oil, for example. Along with pollutants certain fish acquire high levels of EPA/DHA as predatory species. However, the origin of EPA/DHA in aquatic ecosystems is algae. Certain microalgae produce high levels of EPA or DHA. Now, organically produced DHA-rich microalgae oil is available. Clinical trials with DHA-rich oil indicate comparable efficacies to fish oil for protection from cardiovascular risk factors by lowering plasma triglycerides and oxidative stress. This review discusses 1) omega-3 fatty acids in nutrition and medicine; 2) omega-3s in physiology and gene regulation; 3) possible protective mechanisms of EPA/DHA in major diseases such as coronary heart disease, atherosclerosis, cancer and type 2 diabetes; 4) EPA and DHA requirements considering fish oil safety; and 5) microalgae EPA and DHA-rich oils and recent clinical results.
Curr Diabetes Rev 2007 Aug
PMID:Omega-3 fatty acids for nutrition and medicine: considering microalgae oil as a vegetarian source of EPA and DHA. 1822 Jun 72


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