linoleic-acid and Diabetes-Mellitus--Type-2

As heart disease and type 2 diabetes mellitus (T2DM) cases continue to rise, identifying lifestyle modifications to prevent cardiometabolic disease (CMD) is urgently needed. Clinical evidence consistently shows that higher dietary or biomarker levels of linoleic acid (LA; 18:2n6) reduce metabolic syndrome (Mets) and reduce the risk for CMD. Yet, dietary recommendations to include LA as part of a lifestyle plan with the goal of preventing CMD remain elusive.. Clinical interventions consistently show that dietary the addition of LA to the diet improves body composition, dyslipidemia, and insulin sensitivity while reducing systemic inflammation and fatty liver. These effects of LA position dietary LA-rich oils as a potential dietary strategy to aid in preventing CMD. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that are cellular targets for many polyunsaturated fatty acids and oxylipin metabolites. PPAR activation can regulate dyslipidemia, insulin sensitivity, adipose biology, and inflammation, potentially explaining the plethora of effects of dietary LA on aspects of CMD.. Unraveling the cellular mechanism(s) of LA to impact PPAR activity may reset a false dogma that LA, as a member of the omega-6 fatty acid family, promotes inflammation in humans. In fact, LA appears to reduce inflammation and reduce risk for CMD.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fatty Acids, Omega-6; Humans; Inflammation; Insulin Resistance; Linoleic Acid; Peroxisome Proliferator-Activated Receptors

Dietary fat quality, especially the intake of specific types of fatty acids, impacts the risk of many chronic diseases, including cardiovascular diseases, certain cancers and type 2 diabetes (T2DM). A recent pooled analysis involving 20 studies from around the world revealed that higher linoleic acid (18:2n-6 LA) biomarker is associated with dose-dependent decreases in the incidence of T2DM. This latest study corroborates earlier cross-sectional studies and intervention trials showing that biomarkers of LA intake are associated with reduced risk of T2DM and better glycemic control and/or insulin sensitivity. This review highlights key clinical trials that have evaluated the role of LA in glycemia and the related condition, insulin sensitivity.

Topics: Blood Glucose; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dietary Fats; Humans; Insulin Resistance; Linoleic Acid; Neoplasms; Risk

The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes.. We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis.. Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23·3-28·4 kg/m. Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful.. Funders are shown in the appendix.

Topics: Adult; Arachidonic Acid; Biomarkers; Cohort Studies; Diabetes Mellitus, Type 2; Fatty Acids, Omega-6; Humans; Incidence; Linoleic Acid; Prospective Studies; Risk Factors; Statistics as Topic

n-6 Fatty acids, like n-3 fatty acids, play essential roles in many biological functions. Because n-6 fatty acids are the precursors of proinflammatory eicosanoids, higher intakes have been suggested to be detrimental, and the ratio of n-6 to n-3 fatty acids has been suggested by some to be particularly important. However, this hypothesis is based on minimal evidence, and in humans higher intakes of n-6 fatty acids have not been associated with elevated levels of inflammatory markers. n-6 Fatty acids have long been known to reduce serum total and low-density lipoprotein cholesterol, and increases in polyunsaturated fat intake, mostly as n-6 fatty acids, were a cornerstone of dietary advice during the 1960s and 1970s. In the United States, for example, intake of n-6 fatty acids doubled and coronary heart disease (CHD) mortality fell by 50% over a period of several decades. In a series of relatively small, older randomized trials, in which intakes of polyunsaturated fat were increased (even up to 20% of calories), rates of CHD were generally reduced. In a more recent detailed examination of fatty acid intake within the Nurses' Health Study, greater intake of linoleic acid, up to about 8% of energy, has been strongly related to lower incidence of myocardial infarction or CHD death. Because n-3 fatty acids were also related inversely to risk of CHD, the ratio was unrelated to risk. n-6 Fatty acids reduce insulin resistance, probably by acting as a ligand for peroxisome proliferator-activated receptors-gamma, and intakes have been inversely related to risk of type 2 diabetes. Adequate intakes of both n-6 and n-3 fatty acids are essential for good health and low rates of cardiovascular disease and type 2 diabetes, but the ratio of these fatty acids is not useful. Reductions of linoleic acid to "improve" this ratio would likely increase rates of cardiovascular disease and diabetes.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fatty Acids, Omega-6; Humans; Inflammation; Insulin Resistance; Linoleic Acid; Lipids; NF-kappa B; Receptors, Tumor Necrosis Factor

Type 2 diabetes is associated with significantly accelerated rates of macrovascular complications such as atherosclerosis. Emerging evidence now indicates that atherosclerosis is an inflammatory disease and that certain inflammatory markers may be key predictors of diabetic atherosclerosis. Proinflammatory cytokines and cellular adhesion molecules expressed by vascular and blood cells during stimulation by growth factors and cytokines seem to play major roles in the pathophysiology of atherosclerosis and diabetic vascular complications. However, more recently, data suggest that inflammatory responses can also be elicited by smaller oxidized lipids that are components of atherogenic oxidized low-density lipoprotein or products of phospholipase activation and arachidonic acid metabolism. These include oxidized lipids of the lipoxygenase and cyclooxygenase pathways of arachidonic acid and linoleic acid metabolism. These lipids have potent growth, vasoactive, chemotactic, oxidative, and proinflammatory properties in vascular smooth muscle cells, endothelial cells, and monocytes. Cellular and animal models indicate that these enzymes are induced under diabetic conditions, have proatherogenic effects, and also mediate the actions of growth factors and cytokines. This review highlights the roles of the inflammatory cyclooxygenase and 12/15-lipoxygenase pathways in the pathogenesis of diabetic vascular disease. Evidence suggests that inflammatory responses in the vasculature can be elicited by small oxidized lipids that are components of oxidized low-density lipoprotein or products of the lipoxygenase and cyclooxygenase pathways of arachidonic and linoleic acid metabolism. This review evaluates these inflammatory and proatherogenic pathways in the pathogenesis of diabetic vascular disease.

Topics: Animals; Arachidonic Acids; Arteriosclerosis; Chemotaxis; Coronary Restenosis; Cyclooxygenase 2; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelium, Vascular; Gene Expression Regulation; Humans; Hydroxyeicosatetraenoic Acids; Inflammation Mediators; Insulin Resistance; Linoleic Acid; Lipoxygenase; Membrane Proteins; Mice; Models, Biological; Muscle, Smooth, Vascular; Prostaglandin-Endoperoxide Synthases; Signal Transduction

Isomers of conjugated linoleic acid (CLA) are found in beef, lamb and dairy products. Diets containing CLA reduce adipose mass in various depots of experimental animals. In addition, CLA delays the onset of diabetes in the ZDF rat model for obesity-linked type 2 diabetes mellitus. We hypothesize that there would be an inverse association of CLA with body weight and serum leptin in subjects with type 2 diabetes mellitus. In this double-blind study, subjects with type 2 diabetes mellitus were randomized into one of two groups receiving either a supplement containing mixed CLA isomers (CLA-mix; 8.0 g daily, 76% pure CLA; n = 12) or a supplement containing safflower oil (placebo; 8.0 g daily safflower oil, n = 9) for 8 wk. The isomers of CLA in the CLA-mix supplement were primarily c9t11-CLA ( approximately 37%) and t10c12-CLA ( approximately 39%) in free fatty acid form. Plasma levels of CLA were inversely associated with body weight (P < 0.05) and serum leptin levels (P < 0.05). When levels of plasma t10c12-CLA isomer were correlated with changes in body weight or serum leptin, t10c12-CLA, but not c9t11-CLA, was inversely associated with body weights (P < 0.05) and serum leptin (P < 0.02). These findings strongly suggest that the t10c12-CLA isomer may be the bioactive isomer of CLA to influence the body weight changes observed in subjects with type 2 diabetes. Future studies are needed to determine a causal relationship, if any, of t10c12-CLA or c9t11-CLA to modulate body weight and composition in subjects with type 2 diabetes. Furthermore, determining the ability of CLA isomers to influence glucose and lipid metabolism as well as markers of insulin sensitivity is imperative to understanding the role of CLA to aid in the management of type 2 diabetes and other related conditions of insulin resistance.

Topics: Adult; Animals; Body Weight; Diabetes Mellitus, Type 2; Humans; Leptin; Linoleic Acid; Obesity; Randomized Controlled Trials as Topic

Topics: Arteriosclerosis; Blood Glucose; Carbohydrate Metabolism; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Glucose Tolerance Test; Humans; Intestinal Absorption; Linoleic Acid; Linoleic Acids; Lipids

The recommendations for dietary fats in patients with type 2 diabetes are based largely on the impact of fatty acids on fasting serum lipid and glucose concentrations. How fatty acids affect postprandial insulin, glucose, and triglyceride concentrations, however, remains unclear. The objective of this study was to study the effect of fatty acids on postprandial insulin, glucose, and triglyceride responses.. Test meals rich in palmitic acid, linoleic acid, oleic acid, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and containing 1,000 kcal each were administered in a randomized crossover design to 11 type 2 diabetic subjects. Serum insulin, glucose, and triglyceride concentrations were measured for 360 min. All subjects received an isoenergetic diet of constant composition throughout the study.. According to repeated-measures ANOVA, the insulin (P = 0.0002) but not glucose (P = 0.10) response was significantly different between meals. The insulin response was lower to meals rich in oleic acid or EPA and DHA than to meals rich in palmitic acid or linoleic acid (P < 0.01). The triglyceride response did not reach statistical significance (P = 0.06) but tended to be lower with EPA and DHA than with the other fatty acids. Similar trends were seen for area under the curve (AUC) and incremental AUC for serum insulin and triglycerides, but the differences were not significant.. In comparison with palmitic acid and linoleic acid, oleic acid or EPA and DHA may modestly lower insulin response in patients with type 2 diabetes without deteriorating the glucose response. EPA and DHA may also reduce the triglyceride response.

Topics: Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Diet, Diabetic; Dietary Fats; Docosahexaenoic Acids; Eicosapentaenoic Acid; Humans; Hypoglycemic Agents; Insulin; Linoleic Acid; Lipids; Male; Oleic Acid

Isomers of conjugated linoleic acid (CLA) are found in beef, lamb and dairy products. Diets containing CLA reduce adipose mass in various depots of experimental animals. In addition, CLA delays the onset of diabetes in the ZDF rat model for obesity-linked type 2 diabetes mellitus. We hypothesize that there would be an inverse association of CLA with body weight and serum leptin in subjects with type 2 diabetes mellitus. In this double-blind study, subjects with type 2 diabetes mellitus were randomized into one of two groups receiving either a supplement containing mixed CLA isomers (CLA-mix; 8.0 g daily, 76% pure CLA; n = 12) or a supplement containing safflower oil (placebo; 8.0 g daily safflower oil, n = 9) for 8 wk. The isomers of CLA in the CLA-mix supplement were primarily c9t11-CLA ( approximately 37%) and t10c12-CLA ( approximately 39%) in free fatty acid form. Plasma levels of CLA were inversely associated with body weight (P < 0.05) and serum leptin levels (P < 0.05). When levels of plasma t10c12-CLA isomer were correlated with changes in body weight or serum leptin, t10c12-CLA, but not c9t11-CLA, was inversely associated with body weights (P < 0.05) and serum leptin (P < 0.02). These findings strongly suggest that the t10c12-CLA isomer may be the bioactive isomer of CLA to influence the body weight changes observed in subjects with type 2 diabetes. Future studies are needed to determine a causal relationship, if any, of t10c12-CLA or c9t11-CLA to modulate body weight and composition in subjects with type 2 diabetes. Furthermore, determining the ability of CLA isomers to influence glucose and lipid metabolism as well as markers of insulin sensitivity is imperative to understanding the role of CLA to aid in the management of type 2 diabetes and other related conditions of insulin resistance.

Topics: Adult; Animals; Body Weight; Diabetes Mellitus, Type 2; Humans; Leptin; Linoleic Acid; Obesity; Randomized Controlled Trials as Topic

The aim of the present study was to compare the effects of a low-fat diet enriched with oleic acid to those of a low-fat diet enriched with linoleic acid on fasting lipids, postprandial lipemia, and oxidative susceptibility of low-density lipoprotein (LDL) in patients with type 2 diabetes mellitus (DM). In a 3-wk randomized crossover study, eight patients with type 2 DM were given an experimental low-fat diet enriched with either oleic acid or linoleic acid. The oleic-acid-enriched diet contained 5, 15, and 5%, energy from saturated, monounsaturated, and polyunsaturated fatty acids, and the linoleic-acid-enriched diet contained 5, 5, and 15% energy from saturated, monounsaturated, and polyunsaturated fatty acids, respectively. In addition to evaluating the fasting lipids and oxidative susceptibility of LDL, we evaluated postprandial lipemia using an oral fat load at the end of each 3-wk dietary phase. There were no significant differences in fasting lipid profile or lag time of LDL oxidation between the two experimental dietary phases. The average and maximal increments of remnant-like particle (RLP) cholesterol levels during oral fat load were significantly higher after the oleic-acid-enriched dietary phase than after the linoleic-acid-enriched dietary phase. The area under the curve of RLP cholesterol was also significantly larger after the oleic-acid-enriched dietary phase than after the linoleic-acid-enriched dietary phase. These results suggest that the oleic-acid-enriched diet was associated with increased formation of postprandial chylomicron remnants compared with the linoleic-acid-enriched diet.

Topics: Aged; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Diabetes Mellitus, Type 2; Diet, Fat-Restricted; Dietary Fats, Unsaturated; Energy Intake; Exercise; Fasting; Female; Food; Humans; Linoleic Acid; Lipid Peroxidation; Lipids; Lipoproteins, LDL; Male; Middle Aged; Oleic Acid; Postmenopause; Triglycerides

It has been shown recently that troglitazone exerts an anti-inflammatory effect, in vitro, and in experimental animals. To test these properties in humans, we investigated the effect of troglitazone on the proinflammatory transcription factor nuclear factor-kappaB and its inhibitory protein IkappaB in mononuclear cells (MNC) and plasma soluble intracellular adhesion molecule-1, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, and C-reactive protein. We also examined the effect of troglitazone on reactive oxygen species generation, p47(phox) subunit expression, 9-hydroxyoctadecadienoic acid (9-HODE), 13-HODE, o-tyrosine, and m-tyrosine in obese patients with type 2 diabetes. Seven obese patients with type 2 diabetes were treated with troglitazone (400 mg/day) for 4 weeks. Blood samples were obtained at weekly intervals. Nuclear factor-kappaB binding activity in MNC nuclear extracts was significantly inhibited after troglitazone treatment at week 1 and continued to be inhibited up to week 4. On the other hand, IkappaB protein levels increased significantly after troglitazone treatment at week 1, and this increase persisted throughout the study. Plasma monocyte chemoattractant protein-1 and soluble intracellular adhesion molecule-1 concentrations did not decrease significantly after troglitazone treatment, although there was a trend toward inhibition. Reactive oxygen species generation by polymorphonuclear cells and MNC, p47(phox) subunit protein quantities, plasminogen activator inhibitor-1, and C-reactive protein levels decreased significantly after troglitazone intake. 13-HODE/linoleic acid and 9-HODE/linoleic acid ratios also decreased after troglitazone intake. However, o-tyrosine/phenylalanine and m-tyrosine/phenylalanine ratios did not change significantly. These data show that troglitazone has profound antiinflammatory effects in addition to antioxidant effects in obese type 2 diabetics; these effects may be relevant to the recently described beneficial antiatherosclerotic effects of troglitazone at the vascular level.

Topics: Adult; Anti-Inflammatory Agents; Blood Glucose; C-Reactive Protein; Chemokine CCL2; Cholesterol; Chromans; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; I-kappa B Proteins; Insulin; Intercellular Adhesion Molecule-1; Leukocytes, Mononuclear; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Male; Middle Aged; NADPH Oxidases; Neutrophils; NF-kappa B; Obesity; Phenylalanine; Phosphoproteins; Plasminogen Activator Inhibitor 1; Reactive Oxygen Species; Thiazoles; Thiazolidinediones; Triglycerides; Troglitazone; Tyrosine

Polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs) have been shown to positively affect blood lipids; however, their comparative effects on insulin sensitivity are unclear.. Our objective was to investigate whether chronic intake of MUFAs or PUFAs improves insulin sensitivity in people with type 2 diabetes via stimulation of the endogenous gut hormone glucagon-like peptide 1 [7-36] amide (GLP-1).. Nine overweight people with type 2 diabetes received isoenergetic high-MUFA (20.3 +/- 3.5% of total energy) or high-PUFA (13.4 +/- 1. 3%) diets for 24 d in a randomized, double-blind crossover design.. Weight and glycemic control remained stable throughout the study. Despite a significant change in the plasma triacylglycerol linoleic-oleic acid ratio (L:O) with both diets (MUFA: from 0.46 +/- 0.03 to 0.29 +/- 0.02, P: < 0.005; PUFA: from 0.36 +/- 0.04 to 0.56 +/- 0.05, P: < 0.05) and the phospholipid L:O (1.7 +/- 0.1 to 2.0 +/- 0.3; P: = 0.04) during consumption of the PUFA diet, this change was not associated with a change in insulin sensitivity, measured by the short-insulin-tolerance test. There was a significant reduction in the ratio of total to HDL cholesterol during consumption of the PUFA diet (5.2 +/- 0.4 compared with 4.7 +/- 0.3; P: = 0.005) but no change with the MUFA diet. There was no change in the fasting or postprandial incremental area under the curve in response to an identical standard test meal for glucose, insulin, triacylglycerol, nonesterified fatty acids, or GLP-1.. Over the 3-wk intervention period, diet-induced change in the triacylglycerol or phospholipid L:O was not associated with either increased stimulation of GLP-1 or a change in insulin sensitivity in people with type 2 diabetes.

Topics: Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Dietary Fats, Unsaturated; Double-Blind Method; Fatty Acids; Fatty Acids, Monounsaturated; Fatty Acids, Nonesterified; Fatty Acids, Unsaturated; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Linoleic Acid; Oleic Acid; Peptide Fragments; Protein Precursors; Triglycerides

The effects of intensive insulin therapy on metabolic control, fatty acid metabolism and platelet function were studied in 18 non-obese non-insulin-dependent diabetics (NIDDs) with secondary failure to oral antidiabetic drugs (OAD). Patients were randomly allocated either to continue maximal OAD (Group I, n = 9) or to receive a multiple injection regimen of insulin therapy (Group II, n = 9) for a 6-month period. At baseline both groups were identical for clinical and biological parameters. At study day 180, fasting blood glucose (P < 0.01) and mean capillary blood glucose (P < 0.05) were reduced in group II but the difference between HbA1 percentages remained non-significant. At study day 60, in total plasma lipids, oleic acid was lower (P < 0.05), linoleic acid (P < 0.05) and the sum of polunsaturated fatty acids (PUFA) (P < 0.05) were higher in group II than I. In triglycerides, palmitic acid was lower in group II at study days 60 (P < 0.01) and 180 (P < 0.05), whereas gamma-linolenic acid was decreased (P < 0.05) at study day 180 only. A similar change was noted in cholesterol esters for gamma-linolenic acid at study day 60 (P < 0.05). No difference was noted between both groups for platelet agregation, insulin sensitivity and clinical parameters despite a significant increase in body weight in group II at study day 180. Positive correlations were obtained between the content of different lipid fractions in some PUFA and the glucose clearance. We conclude that optimized insulin therapy in NIDDs with secondary failure to OAD leads to a transient improvement in glucidic and lipidic metabolism but has no significant effect upon platelet aggregation and insulin sensitivity.

Topics: Adenosine Diphosphate; Administration, Oral; Adult; Aged; Blood Glucose; Body Mass Index; Cholesterol Esters; Diabetes Mellitus, Type 2; Fatty Acids; Fatty Acids, Nonesterified; Fatty Acids, Unsaturated; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Linoleic Acid; Linoleic Acids; Middle Aged; Oleic Acid; Oleic Acids; Phospholipids; Platelet Aggregation; Time Factors; Treatment Failure; Triglycerides

One hundred and forty nine diabetic patients were ophthalmologically assessed seven years after randomisation to a low carbohydrate or modified fat diet (rich in linoleic acid). Glycaemic control, regardless of the type of diet, was a major determinant of the development of retinopathy. Poorly controlled patients (haemoglobin A1c greater than 8%) with low levels of linoleic acid in cholesterol ester had a significantly greater frequency of retinopathy than well controlled patients or patients with similarly unsatisfactory control but higher levels of linoleic acid. The findings support an earlier suggestion that linoleic acid might protect against diabetic retinopathy.

Topics: Cholesterol Esters; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Diet, Diabetic; England; Fatty Acids, Unsaturated; Female; Glycated Hemoglobin; Humans; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Prospective Studies; Random Allocation

The identification of nutritional patterns associated with the development of type 2 diabetes (T2D) might help lead the way to a more efficient and personalized nutritional intervention. Our study is aimed at evaluating the association between fatty acids (FA) in red blood cell (RBC) membranes, as a quantitative biomarker of regular dietary fat intake, and incident type 2 diabetes in a Spanish population. We included 1032 adult Spaniards (57% women, age 49 ± 15 years, 18% prediabetes), without diabetes at study entry, from the Di@bet.es cohort. Incident diabetes was diagnosed at the end of the study follow-up. The FA percentage in RBC was determined at baseline by gas chromatography. Participants were followed on average 7.5 ± 0.6 years. Lower percentages of linoleic acid (LA), α-linolenic (ALA), and eicosapentaenoic acid (EPA), and higher percentages of docosahexaenoic acid (DHA) in RBC membranes were associated, independently of classical risk factors, with worse glucose metabolism at the end of the study follow-up. In addition, higher percentages of ALA and EPA, and moderate percentages of DHA, were associated with lower risk of diabetes. No significant associations were found for LA and diabetes risk. Dietary patterns rich in vegetables are independently associated with lower risk of both deterioration of glucose regulation and incident diabetes, and should be reinforced for the prevention of diabetes.

Topics: Adult; alpha-Linolenic Acid; Diabetes Mellitus, Type 2; Docosahexaenoic Acids; Eicosapentaenoic Acid; Erythrocytes; Fatty Acids; Fatty Acids, Omega-3; Female; Glucose; Humans; Incidence; Linoleic Acid; Male; Middle Aged; Vegetables

Topics: Diabetes Mellitus, Type 2; Diet; Dietary Fats; Dietary Fats, Unsaturated; Humans; Linoleic Acid

To study plasma and dietary linoleic acid (LA) in relation to type 2 diabetes risk in post-myocardial infarction (MI) patients.. We included 3,257 patients aged 60-80 years (80% male) with a median time since MI of 3.5 years from the Alpha Omega Cohort and who were initially free of type 2 diabetes. At baseline (2002-2006), plasma LA was measured in cholesteryl esters, and dietary LA was estimated with a 203-item food-frequency questionnaire. Incident type 2 diabetes was ascertained through self-reported physician diagnosis and medication use. Hazard ratios (with 95% CIs) were calculated by Cox regressions, in which dietary LA isocalorically replaced the sum of saturated (SFA) and. Mean ± SD circulating and dietary LA was 50.1 ± 4.9% and 5.9 ± 2.1% energy, respectively. Plasma and dietary LA were weakly correlated (Spearman. In our cohort of post-MI patients, plasma LA was inversely related to type 2 diabetes risk, whereas dietary LA was not related. Further research is needed to assess whether plasma LA indicates metabolic state rather than dietary LA in these patients.

Topics: Aged; Aged, 80 and over; Biomarkers; Cohort Studies; Diabetes Mellitus, Type 2; Diet; Dietary Fats; Female; Follow-Up Studies; Humans; Linoleic Acid; Male; Middle Aged; Myocardial Infarction; Nutrition Surveys; Prospective Studies; Risk Factors; Trans Fatty Acids

Monk fruit extract (MFE) is a natural sweetener that has been used as an ingredient of food and pharmaceutical products. The effects of feeding synbiotic yogurt fortified with MFE to rats with type 2 diabetes induced by high-fat diet and streptozotocin on serum lipid levels and hepatic AMPK signaling pathway were evaluated. Results showed that oral administration of the synbiotic yogurt fortified with MFE could improve serum lipid levels, respiratory exchange rate, and heat level in type 2 diabetic rats. Transcriptome analysis showed that synbiotic yogurt fortified with MFE may affect the expression of genes involved in binding, catalytic activity, and transporter activity. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that these differentially expressed genes were related to AMPK signaling pathway, linoleic acid metabolism, and α-linolenic acid metabolism. Western blotting confirmed that synbiotic yogurt fortified with MFE could activate AMPK signaling and improve the protein level of the hepatic gluconeogenic enzyme G6Pase in diabetic rats. The results indicated that MFE could be a novel sweetener for functional yogurt and related products.

Topics: alpha-Linolenic Acid; AMP-Activated Protein Kinases; Animals; Body Weight; Cucurbitaceae; Diabetes Mellitus, Type 2; Gene Expression Profiling; Glucose-6-Phosphatase; Intracellular Signaling Peptides and Proteins; Linoleic Acid; Lipids; Liver; Male; Phosphoenolpyruvate Carboxykinase (GTP); Plant Extracts; Rats; Respiration; Signal Transduction; Sweetening Agents; Synbiotics; Yogurt

To assess the associations of dietary linoleic acid (LA) and α-linolenic acid (ALA) with type 2 diabetes (T2D) risk in a population-based cohort and further explore the mechanism of action in a high-fat-diet (HFD) induced obese (DIO) mouse model.. The occurrence of T2D among 15 100 Chinese adults from China Health and Nutrition Survey (CHNS, 1997-2011) were followed up for a median of 14 years. The relations of ALA and LA intakes with T2D risk were modified by BMI, with significant associations restricted to obese/overweight subjects. Among them, relative risks (95% confidence intervals) comparing extreme quartiles of intakes were 0.55 (0.32-0.93) in men and 0.53 (0.34-0.85) in women for ALA, while 0.71 (0.41-1.16) in men and 0.56 (0.36-0.89) in women for LA. DIO mice were fed with LA- or ALA-enriched HFD (0.2% wt wt. Long-term intake of LA (for women) and ALA may have a protective effect on T2D development for obese/overweight subjects through sex-specific gut microbiota modulation and gut-adipose axis.

Topics: Adult; alpha-Linolenic Acid; Animals; Blood Glucose; China; Diabetes Mellitus, Type 2; Female; Gastrointestinal Microbiome; Homeostasis; Humans; Linoleic Acid; Longitudinal Studies; Male; Mice, Inbred C57BL; Obesity; Overweight; Sex Factors

This cross-sectional study aimed to assess the association of the fat content in the diet with Diabetic Kidney Disease (DKD) in patients with type 2 diabetes.. Patients from the Diabetes research clinic at Hospital de Clínicas de Porto Alegre (Brazil) were consecutively recruited. The inclusion criterion was the diagnosis of type 2 diabetes. The exclusion criteria were as follows: body mass index >40 kg/m2, heart failure, gastroparesis, diabetic diarrhea, dietary counseling by a registered dietitian during the previous 12 months, and inability to perform the weighed diet records (WDR). The dietary fatty acids (saturated, monounsaturated and polyunsaturated) consumption was estimated by 3-day WDR. Compliance with the WDR technique was assessed by comparison of protein intake estimated from the 3-day WDR and from the 24-h urinary nitrogen output performed on the third day of the WDR period. The presence of DKD was defined as urinary albumin excretion (UAE) ≥ 30 mg / 24 h or/and glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Urinary albumin was measured twice and eGFR was estimated by using the CKD-EPI equation.. A total of 366 patients were evaluated; of these, 33% (n = 121) had DKD. Multivariate analysis showed that the intake of linolenic acid was negatively associated with DKD (OR = 0.57; 95% CI 0.35-0.93; P = 0.024), adjusted for gender, smoking, cardiovascular disease, ACE inhibitors and/or angiotensin receptor blocker use, systolic blood pressure, fasting plasma glucose and HDL cholesterol. In a separate model, similar results were observed for linoleic acid, adjusting to the same co-variables (OR = 0.95; 95% CI 0.91-0.99; P = 0.006).. The lower intake of polyunsaturated fatty acids, especially linolenic and linoleic acid, is associated with chronic kidney disease in patients with type 2 diabetes.

Topics: Aged; alpha-Linolenic Acid; Brazil; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diet Surveys; Dietary Fats; Feeding Behavior; Female; Humans; Linoleic Acid; Male; Middle Aged; Renal Insufficiency, Chronic; Risk Factors

Topics: Asian People; Blood Glucose; Body Fat Distribution; Diabetes Mellitus, Type 2; Fatty Acids; Female; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin Resistance; Intra-Abdominal Fat; Japan; Linear Models; Linoleic Acid; Male; Middle Aged; Subcutaneous Fat, Abdominal; Tomography, X-Ray Computed

Data on the relation between linoleic acid (LA) and alpha-linolenic acid (ALA) and type 2 diabetes mellitus (T2DM) risk are scarce and inconsistent. The aim of this study was to investigate the association of serum LA and ALA with fasting and 2 h post-load plasma glucose and glycated hemoglobin (HbA1c).. This study included 667 participants from third examination (2000) of the population-based Hoorn study in which individuals with glucose intolerance were overrepresented. Fatty acid profiles in serum total lipids were measured at baseline, in 2000. Diabetes risk markers were measured at baseline and follow-up in 2008. Linear regression models were used in cross-sectional and prospective analyses.. In cross-sectional analyses (n = 667), serum LA was inversely associated with plasma glucose, both in fasting conditions (B = -0.024 [-0.045, -0.002]) and 2 h after glucose tolerance test (B = -0.099 [-0.158, -0.039]), but not with HbA1c (B = 0.000 [-0.014, 0.013]), after adjustment for relevant factors. In prospective analyses (n = 257), serum LA was not associated with fasting (B = 0.003 [-0.019, 0.025]) or post-load glucose (B = -0.026 [-0.100, 0.049]). Furthermore, no significant associations were found between serum ALA and glucose metabolism in cross-sectional or prospective analyses.. In this study, serum LA was inversely associated with fasting and post-load glucose in cross-sectional, but not in prospective analyses. Further studies are needed to elucidate the exact role of serum LA and ALA levels and dietary polyunsaturated fatty acids in glucose metabolism.

Topics: Aged; alpha-Linolenic Acid; Blood Glucose; Body Mass Index; Cholesterol; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diet; Exercise; Fatty Acids, Unsaturated; Female; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Linoleic Acid; Male; Middle Aged; Prospective Studies; Risk Factors; Triglycerides

The relations between dietary and/or circulating levels of fatty acids and the development of type 2 diabetes is unclear. Protective associations with the marine omega-3 fatty acids and linoleic acid, and with a marker of fatty acid desaturase activity delta-5 desaturase (D5D ratio) have been reported, as have adverse relations with saturated fatty acids and D6D ratio.. To determine the associations between red blood cell (RBC) fatty acid distributions and incident type 2 diabetes.. Prospective observational cohort study nested in the Women's Health Initiative Memory Study.. General population.. Postmenopausal women.. Self-reported incident type 2 diabetes.. There were 703 new cases of type 2 diabetes over 11 years of follow up among 6379 postmenopausal women. In the fully adjusted models, baseline RBC D5D ratio was inversely associated with incident type 2 diabetes [Hazard Ratio (HR) 0.88, 95% confidence interval (CI) 0.81-0.95) per 1 SD increase. Similarly, baseline RBC D6D ratio and palmitic acid were directly associated with incident type 2 diabetes (HR 1.14, 95% CI 1.04-1.25; and HR 1.24, 95% CI 1.14-1.35, respectively). None of these relations were materially altered by excluding incident cases in the first two years of follow-up. There were no significant relations with eicosapentaenoic, docosahexaenoic or linoleic acids.. Whether altered fatty acid desaturase activities or palmitic acid levels are causally related to the development of type 2 diabetes cannot be determined from this study, but our findings suggest that proportions of certain fatty acids in RBC membranes are associated with risk for type 2 diabetes.

Topics: Aged; Delta-5 Fatty Acid Desaturase; Diabetes Mellitus, Type 2; Erythrocytes; Fatty Acid Desaturases; Fatty Acids, Omega-3; Female; Humans; Incidence; Linoleic Acid; Linoleoyl-CoA Desaturase; Middle Aged; Postmenopause; Proportional Hazards Models; Prospective Studies; United States; Women's Health

The role of n-6 (ω-6) polyunsaturated fatty acids (PUFAs) in type 2 diabetes (T2D) is inconclusive. In addition, little is known about how factors involved in PUFA metabolism, such as zinc, may affect the associations.. We investigated the associations of serum n-6 PUFAs and activities of enzymes involved in PUFA metabolism, Δ5 desaturase (D5D) and Δ6 desaturase (D6D), with T2D risk to determine whether serum zinc concentrations could modify these associations.. The study included 2189 men from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 y and free of T2D at baseline in 1984-1989. T2D was assessed by self-administered questionnaires, by fasting and 2-h oral-glucose-tolerance test blood glucose measurement at re-examination rounds 4, 11, and 20 y after baseline, and by record linkage to the hospital discharge registry and the reimbursement register on diabetes medication expenses. Multivariate-adjusted Cox proportional hazards regression models were used to analyze associations.. During the average follow-up of 19.3 y, 417 men developed T2D. Those with higher estimated D5D activity (extreme-quartile HR: 0.55; 95% CI: 0.41, 0.74; P-trend < 0.001) and higher concentrations of total n-6 PUFAs (HR: 0.54; 95% CI: 0.41, 0.73; P-trend < 0.001), linoleic acid (LA; HR: 0.52; 95% CI: 0.39, 0.70; P-trend < 0.001), and arachidonic acid (AA; HR: 0.62; 95% CI: 0.46, 0.85; P-trend = 0.007) had a lower risk and those with higher concentrations of γ-linolenic acid (GLA; HR: 1.28; 95% CI: 0.98, 1.68; P = 0.021) and dihomo-γ-linolenic acid (DGLA; HR: 1.38; 95% CI: 1.04, 1.84; P-trend = 0.005) and higher D6D activity had a higher (HR: 1.50; 95% CI: 1.14, 1.97; P-trend < 0.001) multivariate-adjusted risk of T2D. Zinc mainly modified the association with GLA on T2D risk, with a higher risk observed among those with serum zinc concentrations above the median (P-interaction = 0.04).. Higher serum total n-6 PUFA, LA, and AA concentrations and estimated D5D activity were associated with a lower risk of incident T2D, and higher GLA and DGLA concentrations and estimated D6D activity were associated with a higher risk. In addition, a higher serum zinc concentration modified the association of GLA on the risk of T2D.

Topics: 8,11,14-Eicosatrienoic Acid; Adult; Arachidonic Acid; Diabetes Mellitus, Type 2; Fatty Acids, Omega-6; Finland; Follow-Up Studies; gamma-Linolenic Acid; Glucose Tolerance Test; Humans; Linoleic Acid; Linoleoyl-CoA Desaturase; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Proportional Hazards Models; Prospective Studies; Risk Factors; Zinc

White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obese individuals, contributes to the development of insulin resistance and type 2 diabetes. n-3 polyunsaturated fatty acids (PUFAs) of marine origin play an important role in the resolution of inflammation and exert beneficial metabolic effects. Using experiments in mice and overweight/obese patients with type 2 diabetes, we elucidated the structures of novel members of fatty acid esters of hydroxy fatty acids-lipokines derived from docosahexaenoic acid (DHA) and linoleic acid, which were present in serum and WAT after n-3 PUFA supplementation. These compounds contained DHA esterified to 9- and 13-hydroxyoctadecadienoic acid (HLA) or 14-hydroxydocosahexaenoic acid (HDHA), termed 9-DHAHLA, 13-DHAHLA, and 14-DHAHDHA, and were synthesized by adipocytes at concentrations comparable to those of protectins and resolvins derived from DHA in WAT. 13-DHAHLA exerted anti-inflammatory and proresolving properties while reducing macrophage activation by lipopolysaccharides and enhancing the phagocytosis of zymosan particles. Our results document the existence of novel lipid mediators, which are involved in the beneficial anti-inflammatory effects attributed to n-3 PUFAs, in both mice and humans.

Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue, White; Animals; Anti-Inflammatory Agents; Cells, Cultured; Diabetes Mellitus, Type 2; Docosahexaenoic Acids; Esters; Fatty Acids, Unsaturated; Humans; Inflammation; Insulin Resistance; Linoleic Acid; Lipopolysaccharides; Macrophage Activation; Male; Mice; Mice, Inbred C57BL; Obesity; Phagocytosis

Metabolomics has provided new insight into diabetes risk assessment. In this study we characterised the human serum metabolic profiles of participants in the Singapore Chinese Health Study cohort to identify metabolic signatures associated with an increased risk of type 2 diabetes.. In this nested case-control study, baseline serum metabolite profiles were measured using LC-MS and GC-MS during a 6-year follow-up of 197 individuals with type 2 diabetes but without a history of cardiovascular disease or cancer before diabetes diagnosis, and 197 healthy controls matched by age, sex and date of blood collection.. A total of 51 differential metabolites were identified between cases and controls. Of these, 35 were significantly associated with diabetes risk in the multivariate analysis after false discovery rate adjustment, such as increased branched-chain amino acids (leucine, isoleucine and valine), non-esterified fatty acids (palmitic acid, stearic acid, oleic acid and linoleic acid) and lysophosphatidylinositol (LPI) species (16:1, 18:1, 18:2, 20:3, 20:4 and 22:6). A combination of six metabolites including proline, glycerol, aminomalonic acid, LPI (16:1), 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid and urea showed the potential to predict type 2 diabetes in at-risk individuals with high baseline HbA1c levels (≥6.5% [47.5 mmol/mol]) with an AUC of 0.935. Combined lysophosphatidylglycerol (LPG) (12:0) and LPI (16:1) also showed the potential to predict type 2 diabetes in individuals with normal baseline HbA1c levels (<6.5% [47.5 mmol/mol]; AUC = 0.781).. Our findings show that branched-chain amino acids and NEFA are potent predictors of diabetes development in Chinese adults. Our results also indicate the potential of lysophospholipids for predicting diabetes.

Topics: Amino Acids, Branched-Chain; Asian People; Blood Glucose; Case-Control Studies; Chromatography, Liquid; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Furans; Gas Chromatography-Mass Spectrometry; Glycated Hemoglobin; Glycerol; Humans; Linoleic Acid; Lysophospholipids; Metabolomics; Oleic Acid; Proline; Propionates; Urea

The significance of erythrocyte membrane fatty acids (EMFAs) and their ratios to predict hyperglycemia and incident type 2 diabetes is unclear.. We investigated EMFAs as predictors of the worsening of hyperglycemia and incident type 2 diabetes in a 5-y follow-up of a population-based study.. We measured EMFAs in 1346 Finnish men aged 45-73 y at baseline [mean ± SD age: 55 ± 6 y; body mass index (in kg/m(2)): 26.5 ± 3.5]. Our prospective follow-up study included only men who were nondiabetic at baseline and who had data available at the 5-y follow-up visit (n = 735).. Our study showed that, after adjustment for confounding factors, palmitoleic acid (16:1n-7; P = 2.8 × 10(-7)), dihomo-γ-linolenic acid (20:3n-6; P = 2.3 × 10(-4)), the ratio of 16:1n-7 to 16:0 (P = 1.6 × 10(-8)) as a marker of stearoyl coenzyme A desaturase 1 activity, and the ratio of 20:3n-6 to 18:2n-6 (P = 9.4 × 10(-7)) as a marker of Δ(6)-desaturase activity significantly predicted the worsening of hyperglycemia (glucose area under the curve in an oral-glucose-tolerance test). In contrast, linoleic acid (18:2n-6; P = 0.0015) and the ratio of 18:1n-7 to 16:1n-7 (P = 1.5 × 10(-9)) as a marker of elongase activity had opposite associations. Statistical significance persisted even after adjustment for baseline insulin sensitivity, insulin secretion, and glycemia. Palmitoleic acid (P = 0.010) and the ratio of 16:1n-7 to 16:0 (P = 0.004) nominally predicted incident type 2 diabetes, whereas linoleic acid had an opposite association (P = 0.004), and n-3 polyunsaturated fatty acids did not show any associations.. EMFAs and their ratios are associated longitudinally with changes in glycemia and the risk type 2 diabetes.

Topics: 8,11,14-Eicosatrienoic Acid; Aged; Biomarkers; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Erythrocyte Membrane; Fatty Acids; Fatty Acids, Monounsaturated; Fatty Acids, Omega-3; Finland; Follow-Up Studies; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Insulin Resistance; Insulin Secretion; Linear Models; Linoleic Acid; Male; Middle Aged; Prospective Studies; Risk Factors; Stearoyl-CoA Desaturase; White People

The present study involves the determination of antioxidant capacity and in vitro α-amylase and lipase inhibitory activity of the Crotalaria juncea Linn extract. The content of polyphenols, flavonoids, and tannins in the extracts was estimated by spectrophotometry. Antioxidant activity on goat liver lipid peroxidation and linoleic acid emulsion were determined and α-amylase and lipase inhibitory activity was also evaluated. All the extracts had shown antioxidant property, α-amylase, and lipase inhibitory properties. Aqueous extract was found to show maximum antioxidant activity on goat liver. Antilipid peroxidation and antioxidant activity were determined to be 66.94 ± 0.616 (p < .01) and 59.54 ± 0.2 (p < .01), respectively. Maximum α-amylase and lipase inhibitory activities of 71.42 ± 1.37 (p < .01) and 57.14 ± 2.74% (p < .01), respectively, were exhibited by macerated methanol extract. The results had shown that all the extracts exhibited low inhibition and antioxidant activity as compared to standard.

Topics: alpha-Amylases; Animals; Antioxidants; Crotalaria; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Flavonoids; Goats; Hypoglycemic Agents; Linoleic Acid; Lipase; Lipid Peroxidation; Liver; Plant Extracts; Polyphenols; Tannins

Because alterations in blood fatty acid (FA) composition by dietary lipids are associated with insulin resistance and related metabolic disorders, we hypothesized that serum phospholipid FA composition would reflect the early alteration of fasting glycemic status, even in people without metabolic syndrome (MetS). To examine this hypothesis, serum phospholipid FA, desaturase activities, fasting glycemic status, and cardiometabolic parameters were measured in study participants (n = 1022; 30-69 years; male, n = 527; female, n = 495; nondiabetics without disease) who were stratified into normal fasting glucose (NFG) and impaired fasting glucose (IFG) groups. Total monounsaturated FA (MUFA), oleic acid (OA; 18:1n-9), dihomo-γ-linolenic acid (DGLA; 20:3n-6), Δ-9-desaturase activity (D9D; 18:1n-9/18:0), and DGLA/linoleic acid (20:3n-6/18:2n-6) in serum phospholipids were significantly higher in IFG subjects than NFG controls. Study subjects were subdivided into 4 groups, based on fasting glucose levels and MetS status. Palmitoleic acid (16:1n-7) was highest in IFG-MetS and lowest in NFG-non-MetS subjects. Oleic acid and D9D were higher in IFG-MetS than in the other 3 groups. Dihomo-γ-linolenic acid and DGLA/linoleic acid were higher in MetS than in non-MetS, regardless of fasting glucose levels. The high-sensitivity C-reactive proteins (hs-CRPs) and 8-epi-prostaglandin-F2α were higher in IFG than in NFG, regardless of MetS status. Oxidized low-density lipoproteins were higher in IFG-MetS than in the other 3 groups. Total MUFAs, OA, and D9D were positively correlated with homeostasis model assessment of insulin resistance, fasting glucose, triglyceride, hs-CRP, and 8-epi-prostaglandin-F2α. Palmitoleic acid was positively correlated with triglyceride and hs-CRP. Lastly, total MUFA, OA, palmitoleic acid, and D9D were associated with early alteration of fasting glycemic status, therefore suggesting that these may be useful markers for predicting the risk of type 2 diabetes and cardiometabolic diseases.

Topics: 8,11,14-Eicosatrienoic Acid; Biomarkers; Blood Glucose; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dinoprost; Fasting; Fatty Acids, Monounsaturated; Female; Humans; Insulin; Insulin Resistance; Linoleic Acid; Lipoproteins, LDL; Male; Metabolic Syndrome; Middle Aged; Oleic Acid; Phospholipids; Stearoyl-CoA Desaturase; Triglycerides

Epidemiological and clinical studies have reported that olive oil reduces the incidence of cardiovascular disease. However, the mechanisms involved in this beneficial effect have not been delineated. The endothelium plays an important role in blood pressure regulation through the release of potent vasodilator and vasoconstrictor agents such as nitric oxide (NO) and endothelin-1 (ET-1), respectively, events that are disrupted in type 2 diabetes. Extra virgin olive oil contains polyphenols, compounds that exert a biological action on endothelial function. This study analyzes the effects of olive oil polyphenols on endothelial dysfunction using an in vitro model that simulates the conditions of type 2 diabetes. Our findings show that high glucose and linoleic and oleic acids decrease endothelial NO synthase phosphorylation, and consequently intracellular NO levels, and increase ET-1 synthesis by ECV304 cells. These effects may be related to the stimulation of reactive oxygen species production in these experimental conditions. Hydroxytyrosol and the polyphenol extract from extra virgin olive oil partially reversed the above events. Moreover, we observed that high glucose and free fatty acids reduced NO and increased ET-1 levels induced by acetylcholine through the modulation of intracellular calcium concentrations and endothelial NO synthase phosphorylation, events also reverted by hydroxytyrosol and polyphenol extract. Thus, our results suggest a protective effect of olive oil polyphenols on endothelial dysfunction induced by hyperglycemia and free fatty acids.

Topics: Cell Line; Diabetes Mellitus, Type 2; Endothelial Cells; Endothelin-1; Fatty Acids, Nonesterified; Glucose; Linoleic Acid; Nitric Oxide; Nitric Oxide Synthase Type III; Oleic Acid; Olive Oil; Polyphenols

Serum paraoxonase-1(PON-1) activity is decreased in clinical conditions associated with low high-density lipoprotein cholesterol (HDL-C), increased lipid peroxidation and low-grade chronic inflammation, as in type 2 diabetes mellitus (T2DM). Until now there are no data about the association of any fatty acid (FA) with PON-1 activity in T2DM.. Twenty patients with T2DM and 16 healthy controls were included in this cross-sectional study. Serum PON-1 activity, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity as well as plasma glucose, HbA1c, lipids, high-sensitivity C-reactive protein (hs-CRP) and insulin resistance, homeostasis model assessment (HOMA-IR) were measured. The preparation of FA methyl esters and their gas chromatography (GC) analysis were also performed.. HbA1c, plasma insulin, HOMA-IR and triglycerides were higher in patients with T2DM, whereas HDL-C was lower in those subjects. Levels of pro-oxidative enzyme malondialdehyde (MDA) and hs-CRP were significantly higher, and anti-oxidative enzymes SOD and PON-1 activity were decreased in T2DM patients. N-6 PUFAs were higher in T2DM patients, particularly linoleic acid (LA, 18:2 n-6) and arachidonic acid (AA, 20:4 n-6), whereas n-3 PUFA, docosahexaenoic acid (DHA, 22:6 n-3) was lower in T2DM patients. Using regression analysis, we have shown that only LA and DHA independently predicted PON-1 activity of all participants, particularly in patients with T2DM.. Decreased serum PON-1 activity may, in part, be influenced by higher levels of LA and lower levels of DHA in patients with T2DM. Prospective, randomized studies are necessary to confirm these preliminary findings.

Topics: Adult; Aryldialkylphosphatase; Biomarkers; Blood Glucose; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Docosahexaenoic Acids; Female; Glutathione Peroxidase; Glycated Hemoglobin; Humans; Insulin; Linear Models; Linoleic Acid; Male; Middle Aged; Phospholipids; Superoxide Dismutase; Triglycerides

In addition to decreased insulin sensitivity, diabetes is a pathological condition associated with increased inflammation. The ω-3 fatty acids have been proposed as anti-inflammatory agents. Thus, the major goal of this study was to analyze the effects of fatty acid supplementation on both insulin sensitivity and inflammatory status in an animal model of type 2 diabetes. Diabetic rats (Goto-Kakizaki model) were treated with eicosapentaenoic acid (EPA) or linoleic acid at 0.5 g/kg body weigh (bw) dose. In vivo incorporation of (14)C-triolein into adipose tissue was improved by the ω-3 administration. In vitro incubations of adipose tissue slices from EPA-treated rats showed an increase in (14)C-palmitate incorporation into the lipid fraction. These observations were linked with a decreased rate of fatty acid oxidation. EPA treatment resulted in a decreased fatty acid oxidation in incubated strips from extensor digitorum longus (EDL) muscles. The changes in lipid utilization were associated with a decrease in insulin plasma concentration, suggesting an improvement in insulin sensitivity. These changes in lipid metabolism were associated with an activation of AMP-activated protein kinase (AMPK) in white adipose tissue. In addition, EPA treatment resulted in a decreased content of peroxisome proliferator-activated receptor-α (PPARα) and PPARδ and in increased GLUT4 expression in skeletal muscle. Moreover, EPA increased 2-deoxy-D-[(14)C]glucose (2-DOG) uptake in C2C12 myotubes, suggesting an improvement in glucose metabolism. Concerning the inflammatory status, EPA treatment resulted in a decreased gene expression for both tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) both in skeletal muscle and adipose tissue. The data suggest that EPA treatment to diabetic rats clearly improves lipid metabolism although the evidences on insulin sensitization are less clear.

Topics: Adipose Tissue; AMP-Activated Protein Kinases; Animals; Anti-Inflammatory Agents; Diabetes Mellitus, Type 2; Disease Models, Animal; Eicosapentaenoic Acid; Fatty Acids; Humans; Inflammation; Insulin Resistance; Linoleic Acid; Lipid Metabolism; Male; Muscle, Skeletal; Rats

Obesity with excessive levels of circulating free fatty acids (FFAs) is tightly linked to the incidence of type 2 diabetes. Insulin resistance of peripheral tissues and pancreatic β-cell dysfunction are two major pathological changes in diabetes and both are facilitated by excessive levels of FFAs and/or glucose. To gain insight into the mitochondrial-mediated mechanisms by which long-term exposure of INS-1 cells to excess FFAs causes β-cell dysfunction, the effects of the unsaturated FFA linoleic acid (C 18:2, n-6) on rat insulinoma INS-1 β cells was investigated. INS-1 cells were incubated with 0, 50, 250 or 500 μM linoleic acid/0.5% (w/v) BSA for 48 h under culture conditions of normal (11.1 mM) or high (25 mM) glucose in serum-free RPMI-1640 medium. Cell viability, apoptosis, glucose-stimulated insulin secretion, Bcl-2, and Bax gene expression levels, mitochondrial membrane potential and cytochrome c release were examined. Linoleic acid 500 μM significantly suppressed cell viability and induced apoptosis when administered in 11.1 and 25 mM glucose culture medium. Compared with control, linoleic acid 500 μM significantly increased Bax expression in 25 mM glucose culture medium but not in 11.1 mM glucose culture medium. Linoleic acid also dose-dependently reduced mitochondrial membrane potential (ΔΨm) and significantly promoted cytochrome c release from mitochondria in both 11.1 mM glucose and 25 mM glucose culture medium, further reducing glucose-stimulated insulin secretion, which is dependent on normal mitochondrial function. With the increase in glucose levels in culture medium, INS-1 β-cell insulin secretion function was deteriorated further. The results of this study indicate that chronic exposure to linoleic acid-induced β-cell dysfunction and apoptosis, which involved a mitochondrial-mediated signal pathway, and increased glucose levels enhanced linoleic acid-induced β-cell dysfunction.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Cell Line, Tumor; Cell Survival; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Gene Expression Regulation; Hyperglycemia; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Linoleic Acid; Membrane Potential, Mitochondrial; Mitochondria; Osmolar Concentration; Proto-Oncogene Proteins c-bcl-2; Rats; RNA, Messenger; Time Factors

Perturbations of fatty acid content and pattern were recently documented in epididymal and parametrial lipids, as well as plasma, liver, spleen, and brain phospholipids and triglycerides of Goto-Kakizaki rats (GK). This study extends such an investigation to pancreatic islets from both control and GK rats. Groups of 5,500-14,560 islets were obtained from either control or GK rats (n = 3 in each case) and examined for their lipid fatty acid content. In the islet triglycerides, the major difference between control and GK rats, i.e., a higher C18:2ω6 content in GK rats, was similar to that found in liver triglycerides. In the islet phospholipids, however, a number of differences between control and GK rats, concerning saturated, monodesaturated, and long-chain polyunsaturated ω3 and ω6 fatty acids, were often not similar to those found in liver phospholipids. The present study reveals a number of anomalies in the fatty acid pattern of islet phospholipids in GK rats, often differing from those encountered in liver phospholipids. Such a tissue specificity was borne out by the finding that, even in control animals, the situation found in islet phospholipids differed from that recorded in liver phospholipids.

Topics: Animals; Diabetes Mellitus, Type 2; Fatty Acids; Islets of Langerhans; Linoleic Acid; Lipid Metabolism; Male; Organ Specificity; Phospholipids; Rats; Rats, Inbred Strains; Rats, Wistar; Triglycerides

Thiazolidinediones are insulin sensitizing drugs that target the peroxisome proliferator-activated receptor (PPAR) gamma. An n-hexane extract of the flowers of Echinacea purpurea was found to activate PPARgamma without stimulating adipocyte differentiation. Bioassay-guided fractionations yielded five alkamides, of which one was new, and three fatty acids that all activated PPARgamma. The new alkamide hexadeca-2E,9Z,12Z,14E-tetraenoic acid isobutylamide (5) was identified by analysis of spectroscopic data and found to activate PPARgamma with no concurrent stimulation of adipocyte differentiation. Compound 5 was further shown to increase insulin-stimulated glucose uptake. The data suggest that flowers of E. purpurea contain compounds with potential to manage insulin resistance and type 2 diabetes.

Topics: 3T3-L1 Cells; Animals; Denmark; Diabetes Mellitus, Type 2; Echinacea; Fatty Acids, Unsaturated; Flowers; Glucose; Insulin Resistance; Mice; Plants, Medicinal; PPAR gamma

In this letter, we report discovery of diacylphloroglucinol compounds as a new class of GPR40 (FFAR1) agonists. Several diacylphloroglucinols with varying length of acyl functionality and substitution on aromatic hydroxyls were synthesized and evaluated for GPR40 agonism using functional calcium-flux assay. Out of 17 compounds evaluated, 14, 17, 19 and 25 exhibited good GPR40 agonistic activity with EC(50) values ranging from 0.07 to 8 microM (pEC(50) 7.12-5.09), respectively, with maximal agonistic response of 84-102%.

Topics: Animals; Calcium; Chemistry, Pharmaceutical; CHO Cells; Cricetinae; Cricetulus; Diabetes Mellitus, Type 2; Drug Design; Fatty Acids; Humans; Ligands; Models, Chemical; Phloroglucinol; Rats; Receptors, G-Protein-Coupled

Sustained exposure to lipids is deleterious for pancreatic islet function. This could be mediated through increased pancreatic fat following increased dietary fat and in obesity, which has implications for the onset of type 2 diabetes. The aims of this study were to determine changes in extent and composition of pancreatic, hepatic, and visceral fat in mice fed a high-fat diet (HFD, 40% by weight) compared with a control diet (5% fat) of similar fatty acid composition, and to compare composition and extent of pancreatic fat in human type 2 diabetes.. Mice were fed HFD for 3 or 15 weeks. Human postmortem pancreas was examined from subjects with type 2 diabetes (n = 9) and controls (n = 7). Tissue lipid content and composition were determined by gas chromatography and pancreatic adipocyte infiltration quantified by morphometry.. Pancreatic triacylglycerol (TG) content was 20x greater (P < 0.05) in HFD mice and there were more pancreatic perilipin-positive adipocytes compared with controls after 15 weeks. The proportions of 18:1n -9 and 18:2n -6 in pancreatic TG and the 20:4n -6/18:2n -6 ratio in phospholipids, were higher (both P < 0.05) after HFD compared with controls. Human pancreatic TG content was correlated with the proportion of pancreatic perilipin-positive adipocytes (r = 0.64, P < 0.05) and associated with unsaturated fatty acid enrichment (P < 0.05).. Adipocyte infiltration in pancreatic exocrine tissue is associated with high-fat feeding in mice and pancreatic TG content in humans. This alters the fatty acid milieu of the islet which could contribute to islet dysfunction.

Topics: Adipocytes; Adult; Aged; Aged, 80 and over; Animals; Carrier Proteins; Case-Control Studies; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Humans; Intra-Abdominal Fat; Linoleic Acid; Liver; Male; Mice; Mice, Inbred C57BL; Middle Aged; Pancreas; Perilipin-1; Phosphoproteins; Stearoyl-CoA Desaturase; Time Factors; Triglycerides; Up-Regulation

Dietary fatty acids may be associated with diabetes but are difficult to measure accurately.. We aimed to investigate the associations of fatty acids in plasma and diet with diabetes incidence.. This was a prospective case-cohort study of 3737 adults aged 36-72 y. Fatty acid intake (/kJ) and plasma phospholipid fatty acids (%) were measured at baseline, and diabetes incidence was assessed by self-report 4 y later. Logistic regression excluding (model 1) and including (model 2) body mass index and waist-hip ratio was used to calculate odds ratios (ORs) for plasma phospholipid and dietary fatty acids.. In plasma phospholipid, positive associations with diabetes were seen for stearic acid [OR model 1, highest versus lowest quintile: 4.14 (95% CI: 2.65, 6.49), P for trend < 0.0001] and total saturated fatty acids [OR model 1: 3.76 (2.43, 5.81), P for trend < 0.0001], whereas an inverse association was seen for linoleic acid [OR model 1: 0.22 (0.14, 0.36), P for trend < 0.0001]. Dietary linoleic [OR model 1: 1.77 (1.19, 2.64), P for trend = 0.002], palmitic [OR model 1: 1.65 (1.12, 2.43), P for trend = 0.012], and stearic [OR model 1: 1.46 (1.00, 2.14), P for trend = 0.030] acids were positively associated with diabetes incidence before adjustment for body size. Within each quintile of linoleic acid intake, cases had lower baseline plasma phospholipid linoleic acid proportions than did controls.. Dietary saturated fat intake is inversely associated with diabetes risk. More research is required to determine whether linoleic acid is an appropriate dietary substitute.

Topics: Adult; Aged; Blood Glucose; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 2; Dietary Fats; Female; Humans; Insulin; Linoleic Acid; Logistic Models; Male; Middle Aged; Phospholipids; Prospective Studies; Surveys and Questionnaires; Victoria

Results from in vitro studies suggest that selected fatty acids, and especially linoleic acid (LA), can elicit endothelial dysfunction (ED). Because LA is increased in all LDL subfractions in patients with type 2 diabetes, this alteration may contribute to ED associated with diabetes. Lectin-like oxidized LDL receptor-1 (LOX-1) is the major endothelial receptor for oxidized LDL (oxLDL), and uptake of oxLDL through LOX-1 induces ED. To evaluate whether LA may contribute to the upregulation of endothelial LOX-1 in diabetes, we studied the effect of LA on LOX-1 expression in cultured human aortic endothelial cells (HAECs). Treatment of HAECs with LA increased, in a time- and dose-dependent manner, endothelial LOX-1 protein expression. Pretreatment of HAECs with antioxidants and inhibitors of NADPH oxidase, protein kinase C (PKC), and nuclear factor-kappaB (NF-kappaB) inhibited the stimulatory effect of LA on LOX-1 protein expression. Furthermore, in LA-treated HAECs, increased expression of classic PKC isoforms was observed. LA also led to a significant increase in LOX-1 gene expression and enhanced the binding of nuclear proteins extracted from HAECs to the NF-kappaB regulatory element of the LOX-1 gene promoter. Finally, LA enhanced, through LOX-1, oxLDL uptake by endothelial cells. Overall, these results demonstrate that LA enhances endothelial LOX-1 expression through oxidative stress-sensitive and PKC-dependent pathways. This effect seems to be exerted at the transcriptional level and to involve the activation of NF-kappaB. Upregulation of LOX-1 by LA may contribute to ED associated with type 2 diabetes.

Topics: Aorta; Base Sequence; Cells, Cultured; Diabetes Mellitus, Type 2; DNA Primers; Endothelium, Vascular; Humans; Linoleic Acid; Receptors, LDL; Receptors, Oxidized LDL; RNA, Messenger; Scavenger Receptors, Class E; Transcription, Genetic

Hyperlipidemia (HL) impairs cardiac glucose homeostasis, but the molecular mechanisms involved are yet unclear. We examined HL-regulated GLUT4 and peroxisome proliferator-activated receptor (PPAR) gamma gene expression in human cardiac muscle. Compared with control patients, GLUT4 protein levels were 30% lower in human cardiac muscle biopsies from patients with HL and/or type 2 diabetes mellitus, whereas GLUT4 mRNA levels were unchanged. PPARgamma mRNA levels were 30-50% lower in patients with HL and/or diabetes mellitus type 2 than in controls. Reporter studies in H9C2 cardiomyotubes showed that HL in vitro, induced by high levels of arachidonic (AA) stearic, linoleic, and oleic acids (24 h, 200 mum) repressed transcription from the GLUT4 promoter; AA also repressed transcription from the PPARgamma1 and PPARgamma2 promoters. Co-expression of PPARgamma2 repressed GLUT4 promoter activity, and the addition of AA further enhanced this effect. 5'-Deletion analysis revealed three GLUT4 promoter regions that accounted for AA-mediated effects: two repression-mediating sequences at -443/-423 bp and -222/-197 bp, the deletion of either or both of which led to a partial derepression of promoter activity, and a third derepression-mediating sequence at -612/-587 bp that was required for sustaining this derepression effect. Electromobility shift assay further shows that AA enhanced binding to two of the three regions of cardiac nuclear protein(s), the nature of which is still unknown. We propose that HL, exhibited as a high free fatty acid level, modulates GLUT4 gene expression in cardiac muscle via a complex mechanism that includes: (a) binding of AA mediator proteins to three newly identified response elements on the GLUT4 promoter gene and (b) repression of GLUT4 and the PPARgamma genes by AA.

Topics: Aged; Animals; Arachidonic Acid; Biopsy; Blotting, Western; Cell Nucleus; CHO Cells; Chromatography, High Pressure Liquid; Cricetinae; Deoxyglucose; Diabetes Mellitus, Type 2; DNA; DNA Primers; Dose-Response Relationship, Drug; Fatty Acids; Female; Gene Deletion; Gene Expression Regulation; Genes, Reporter; Glucose Transporter Type 4; HeLa Cells; Humans; Linoleic Acid; Lipids; Male; Middle Aged; Models, Biological; Muscles; Myocardium; Oleic Acid; PPAR gamma; Promoter Regions, Genetic; Protein Binding; Proteins; Rats; Response Elements; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stearic Acids; Time Factors; Transcription, Genetic

There is a multitude of data showing that coronary heart disease is affected by the quality of dietary fat. The fatty acid composition of serum lipids has been shown to reflect that of the diet. It is likely that, after myocardial infarction, both the health-care professionals and the patients themselves pay more attention to dietary guidelines. In order to assess the correctness of this assumption, we compared the composition of serum fatty acids in 40 male subjects with a history of myocardial infarction (MI) with that of 40 age-matched controls, both from the FINRISK study. The percentage composition of fatty acids of total serum lipids was analysed by gas chromatography. In comparison with the control group, the MI group had higher body mass index (BMI), a higher prevalence of diabetes, higher level of serum triglycerides and a lower level of serum high-density lipoprotein (HDL) cholesterol, all indicators of the metabolic syndrome. The MI group had higher proportions of serum palmitic (16:0) and oleic acids (18:1), and a lower proportion of linoleic (18:2 n-6) acid than the control group. The metabolic syndrome is accompanied by an elevated level of serum insulin, which is known to enhance the synthesis of saturated and monounsaturated fatty acids, such as 16:0 and 18:1, and to stimulate the activity delta-6 desaturase, decreasing the concentration of linoleic acid. Our results suggest that the observed serum fatty acid composition in subjects with coronary heart disease is dependent on metabolic factors in addition to dietary fatty acid composition.

Topics: Aged; Body Mass Index; Cholesterol, HDL; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Dietary Fats; Fatty Acids; Finland; Humans; Linoleic Acid; Male; Metabolic Syndrome; Middle Aged; Myocardial Infarction; Oleic Acid; Palmitic Acid; Triglycerides

The present study explored the short-term effects of dietary conjugated-linoleic acid (CLA) on liver lipid metabolism in starved/refed Otsuka Long Evans Tokushima Fatty (OLETF) rats. Male OLETF rats (12 weeks old) were starved for 24 hours, then refed for 48 hours with either a CLA diet [7.5% CLA and 7.5% Safflower oil (SAF)] or a SAF control diet (15% SAF). The results demonstrated a 30% reduction of hepatic triglyceride (TG) concentration in the CLA group when compared to the control group. Liver cholesterol concentration was also 26% lower in the CLA fed rats. The activity of mitochondrial carnitine palmitoyltransferase, the rate-limiting enzyme of fatty acid oxidation, was moderately elevated by 1.2-fold in the livers of the CLA group when compared to the control. In contrast, phosphatidate phosphohydrolase, the rate-limiting enzyme for TG synthesis, was found to be 20% lower in the livers of the CLA-fed rats. Therefore, dietary CLA evidently lowers liver lipid concentrations through a reduced TG synthesis and enhanced fatty acid oxidation in starved/refed OLETF rats.

Topics: Animals; Carnitine O-Palmitoyltransferase; Diabetes Mellitus, Type 2; Dietary Fats; Disease Models, Animal; Food; Glucosephosphate Dehydrogenase; Linoleic Acid; Liver; Malate Dehydrogenase; Male; Phosphatidate Phosphatase; Rats; Rats, Inbred OLETF; Starvation; Triglycerides

To examine dietary fat and meat intake in relation to risk of type 2 diabetes.. We prospectively followed 42,504 male participants of the Health Professionals Follow-Up Study who were aged 40-75 years and free of diagnosed diabetes, cardiovascular disease, and cancer in 1986. Diet was assessed by a validated food frequency questionnaire and updated in 1990 and 1994. During 12 years of follow-up, we ascertained 1,321 incident cases of type 2 diabetes.. Intakes of total fat (multivariate RR for extreme quintiles 1.27, CI 1.04-1.55, P for trend=0.02) and saturated fat (1.34, 1.09-1.66, P for trend=0.01) were associated with a higher risk of type 2 diabetes. However, these associations disappeared after additional adjustment for BMI (total fat RR 0.97, CI 0.79-1.18; saturated fat 0.97, 0.79-1.20). Intakes of oleic acid, trans-fat, long-chain n-3 fat, and alpha-linolenic acid were not associated with diabetes risk after multivariate adjustment. Linoleic acid was associated with a lower risk of type 2 diabetes in men <65 years of age (RR 0.74, CI 0.60-0.92, P for trend=0.01) and in men with a BMI <25 kg/m(2) (0.53, 0.33-0.85, P for trend=0.006) but not in older and obese men. Frequent consumption of processed meat was associated with a higher risk for type 2 diabetes (RR 1.46, CI 1.14-1.86 for > or = 5/week vs. <1/month, P for trend <0.0001).. Total and saturated fat intake were associated with a higher risk of type 2 diabetes, but these associations were not independent of BMI. Frequent consumption of processed meats may increase risk of type 2 diabetes.

Topics: Adult; Age Factors; Aged; Body Mass Index; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Fats; Dietary Proteins; Humans; Hypercholesterolemia; Hypertension; Incidence; Linoleic Acid; Male; Meat; Middle Aged; Prospective Studies; Risk Factors; Smoking; Surveys and Questionnaires

Synthetic ligands of the retinoid X receptor (RXR) have shown antidiabetic activity in mice, apparently owing to the fact that they stimulate the transcriptional activity of PPAR-gamma/RXR heterodimers, much like thiazolidinedione drugs. The chlorophyll metabolite phytanic acid has been shown to be a natural ligand for RXR, active in concentrations near its physiological levels. It is thus reasonable to suspect that phytanic acid may have utility for treatment and prevention of human type 2 diabetes. Phytanic acid may mimic or complement various effects of conjugated linoleic acids, which have been shown to activate PPAR-gamma/RXR and prevent rodent diabetes. Administration of hydrolyzed chlorophyll may represent the most cost-effective strategy for raising human tissue levels of phytanic acid.

Topics: Animals; Chlorophyll; Diabetes Mellitus, Type 2; Humans; Linoleic Acid; Mice; Phytanic Acid; Receptors, Cytoplasmic and Nuclear; Transcription Factors

Relationships have been demonstrated between insulin sensitivity and the fatty acid (FA) composition of serum and tissue lipids in adult humans. The present study aimed to investigate the above relationships in different groups of type 2 diabetic patients (DM2). The FA composition of serum phospholipids (S-PL) measured by gas liquid chromatography and insulin action during a 2-step hyperinsulinemic isoglycemic clamp (1 and 10 mU/kg. min) were determined in 21 newly diagnosed DM2 subjects (DMN), in groups of long-term DM2 patients treated with hypoglycemic agents (DMH; n = 21) or diet alone (DMD; n = 11), and in 24 healthy subjects (HS). In diabetics, the metabolic clearance rates of glucose at both insulin levels (MCR(glu)submax and MCR(glu)max) were significantly reduced compared with HS (MCR(glu)submax DMN, 5.35 +/- 2.7 mL x kg(-1) x min(-1), DMH, 5.38 +/- 2.17 mL x kg(-1) x min(-1); DMD, 5.48 +/- 2.35 mL x kg(-1) x min(-1) v HS, 10.9 +/- 3.3 mL x kg(-1) x min(-1); P <.01; MCR(glu)max DMN, 13.3 +/- 3.3 mL x kg(-1) x min(-1); DMH, 12.5 +/- 3.0 mL x kg(-1) x min(-1); DMD, 13.3 +/- 3.0 mL x kg(-1) x min(-1) v HS, 17.4 +/- 3.8 mL x kg(-1) x min(-1); P <.05). Increased contents of highly unsaturated n-6 family FA (P <.01), arachidonic acid in particular (DMN, 10.98% +/- 1.79%; DMD, 10.78% +/- 1.64%; DMH, 10.97% +/- 1.7% v HS, 8.51% +/- 1.53%; P <.001), were found in all groups of diabetics compared with HS, while lower levels of linoleic acid were seen in DMN (P <.001) and DMH (P <.05). The contents of saturated FA and monounsaturated FA were comparable in HS, DMN, and DMD. While in HS there were significant negative correlations between MCR(glu) and the contents of saturated FA and a positive association between insulin action and proportions of linoleic and arachidonic acids, no significant relationships were found in diabetic subjects. Different groups of DM2 patients show an altered FA pattern of S-PL, which is not related to insulin action. The above data support the hypothesis that changes in FA composition may play a role in modulating insulin action in peripheral tissues, but cannot explain the insulin resistance (IR) in DM2 patients.

Topics: Adult; Arachidonic Acid; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Kinetics; Linoleic Acid; Male; Metabolic Clearance Rate; Middle Aged; Phospholipids

Peripheral nerve involvement is a frequent complication of type 1 and type 2 diabetes, and can induce major disability. Almost all types of clinical or electrophysiological disturbances may be present: mononeuropathy involving cranial nerves or a limb; multiple mononeuropathy; proximal acute radiculopathy; distal, symmetric, sensory polyneuropathy; autonomic neuropathy. Physiopathology intricates probably several mechanisms but metabolic dysregulation and ischemia are mainly involved. Despite numerous controlled clinical trials no treatment has demonstrated efficacy for peripheral neuropathy, excepting the optimization of diabetes equilibrium. However, symptomatic treatments are available, particularly for the management of neuropathic pain.

Topics: Acetates; Amines; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbamazepine; Controlled Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Electrophysiology; Gabapentin; gamma-Aminobutyric Acid; Humans; Hyperglycemia; Immunoglobulins, Intravenous; Linoleic Acid; Pain; Prognosis

It may now be feasible to target specific supplemental nutrients to each of the key dysfunctions which conspire to maintain hyperglycemia in type 2 diabetes: bioactive chromium for skeletal muscle insulin resistance, conjugated linoleic acid for adipocyte insulin resistance, high-dose biotin for excessive hepatic glucose output, and coenzyme Q(10) for beta cell failure. Nutritional strategies which disinhibit hepatic fatty acid oxidation (involving hydroxycitrate, carnitine, pyruvate, and other adjuvants) may likewise prove beneficial - in the short term, by decreasing serum free fatty acids and, in the longer term, by promoting regression of visceral obesity. The nutrients and food factors recommended here appear to be safe and well tolerated, and thus may have particular utility for diabetes prevention.

Topics: Biotin; Chromium; Coenzymes; Diabetes Mellitus, Type 2; Dietary Supplements; Fatty Acids, Nonesterified; Humans; Linoleic Acid; Ubiquinone

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Fats; Dietary Fats, Unsaturated; Fatty Acids; Humans; Linoleic Acid; Oleic Acid; Risk Factors

Alterations in low-density lipoprotein (LDL) composition in diabetes affect its function with respect to control of de novo cholesterol synthesis. We examined the effect of 4 weeks of an oleic-acid-rich diet on LDL composition and function in eight Type 2 diabetic and eight non-diabetic control subjects. LDL (density 1.019-1.063 g/l) was isolated by sequential ultracentrifugation. LDL composition was measured and LDL fatty acids were determined by gas liquid chromatography. Cholesterol synthesis was measured by [14C]-acetate incorporation into the freshly isolated mononuclear leucocytes. Fasting blood glucose fell from 9.3 +/- 2.0 to 8.2 +/- 1.2 mmol/l (p < 0.05) and fasting serum insulin increased from 8.3 +/- 2.8 to 10.4 +/- 5.0 mIU/l (p > 0.05) in the diabetic patients. LDL oleic acid increased in the diabetic patients from 18.8 +/- 1.8% to 22.5 +/- 1.9% (p < 0.01) and in the non-diabetic subjects from 19.9 +/- 1.8% to 23.3 +/- 2.8% (p < 0.01). The LDL-esterified to free cholesterol ratios of 3.0 +/- 0.6 and 2.7 +/- 0.2 for the diabetic and non-diabetic patients were similar, and decreased significantly (p < 0.01) to 2.4 +/- 0.5 and 2.2 +/- 0.4, respectively. Baseline [14C]-acetate incorporation was similar in the two groups, and decreased after diet from 437 +/- 239 to 249 +/- 144 ng/g cell protein (p < 0.05) in the diabetic patients. There was a negative correlation between the LDL-esterified to free cholesterol ratio and the ratio of oleic to linoleic acid in the LDL (r = -0.39, p < 0.05) and a negative correlation between fasting blood glucose and LDL oleic acid in the diabetic patients (r = -0.51, p < 0.05). Enrichment of LDL with oleic acid appears to improve its ability to regulate endogenous cholesterol synthesis in both control and diabetic subjects. In the diabetic population, the diet had a favourable effect on glycaemic control.

Topics: Acetates; Adult; Arachidonic Acid; Arteriosclerosis; Blood Glucose; Cholesterol; Diabetes Mellitus, Type 2; Fasting; Female; Humans; Linoleic Acid; Linoleic Acids; Lipoproteins, LDL; Male; Middle Aged; Oleic Acid; Oleic Acids

Coronary artery disease (CAD), hypertension and diabetes mellitus are more common in Indians compared to their incidence in the Western population. The exact reason for this is not known. One of the risk factors for the development of and complications due to CAD, hypertension and diabetes mellitus could be hyperinsulinemia and insulin resistance and low plasma levels of arachidonic acid and eicosapentaenoic acid, metabolites of dietary essential fatty acids (EFAs), cis-linoleic and alpha-linolenic acids. Fatty acid analysis of the plasma phospholipid (PL) fraction of normal Indians showed that they have low concentrations of arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid in comparison to those seen in Canadian and Minnesota (USA) normals. Since insulin can activate EFA metabolism, this alteration in the EFA metabolism may, at least, in part explain the high incidence of CAD, hypertension and diabetes mellitus and insulin resistance and hyperinsulinemia that are common in Indians.

Topics: Adult; alpha-Linolenic Acid; Arachidonic Acid; Coronary Disease; Diabetes Mellitus, Type 2; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Essential; Female; Humans; Hypertension; India; Insulin; Insulin Resistance; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Risk Factors; White People

Conjugated dienes present in the fatty acyl chains of cholesterol esters and triglycerides associated with plasma apolipoprotein B containing lipoproteins of normal and Type 2 (non-insulin-dependent) diabetic patients (n = 17) have been analysed using second derivative electronic absorption spectroscopy. Characteristic spectral patterns for both normal subjects and Type 2 diabetic patients were observed. Cis, trans and trans, trans conjugated dienes in cholesterol esters of lipoprotein B of Type 2 patients and normal subjects were found to be 41.74 +/- 0.51 mg/litre, 8.20 +/- 0.20 mg/litre (p less than 0.01) and 24.70 +/- 0.33 mg/litre, 9.22 +/- 0.06 mg/litre (p less than 0.01), respectively. Levels of these dienes in triglyceride fraction were 21.21 +/- 0.52 mg/litre, 7.72 +/- 0.02 mg/litre (p greater than 0.05) and 15.49 +/- 0.36 mg/litre, 7.91 +/- 0.11 mg/litre (p greater than 0.05), respectively.

Topics: Adult; Apolipoproteins B; Cholesterol Esters; Diabetes Mellitus, Type 2; Female; Humans; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Reference Values; Triglycerides

In non-insulin-dependent diabetes mellitus (NIDDM) patients, microalbuminuria predicts early mortality, predominantly from cardiovascular disease. Increased free radical activity and abnormalities in hemostasis have been implicated in the development of vascular disease. Therefore, we measured markers of free radical activity (nonperoxide-conjugated diene isomer of linoleic acid [PL-9,11-LA'] and lipid peroxides expressed as malondialdehyde [MDA]) along with the hemostatic variables: fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA), and plasmin activity (B beta 15-42) in 24 NIDDM patients (12 patients with microalbuminuria and 12 without microalbuminuria) and in 12 age-matched control subjects. There were no differences in linoleic acid (PL-9,12-LA) concentrations between the three groups. PL-9,11-LA' was elevated in the microalbuminuric patients compared with control subjects (P less than 0.05), but there was no difference between the two diabetic groups. MDA was elevated in the microalbuminuric diabetic patients compared with those patients without microalbuminuria (P less than 0.05) and control subjects (P less than 0.001). MDA was also increased in the patients without microalbuminuria compared with control subjects (P less than 0.01). Except for B beta 15-42, all the hemostatic variables were increased (P less than 0.05) in the diabetic patients compared with control subjects. The microalbuminuric diabetic patients had further increases in vWf (P less than 0.03) and t-PA (P less than 0.03) compared with patients with microalbuminuria. Our study suggests that there is an increase in free radical activity and abnormalities in hemostatic variables favoring a hypercoagulable state in NIDDM, especially in those with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Albuminuria; Analysis of Variance; Biomarkers; Blood Coagulation; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Free Radicals; Humans; Linoleic Acid; Linoleic Acids; Malondialdehyde; Middle Aged; Regression Analysis

The effect of dietary omega-3 polyunsaturated fatty acids on the lipid composition and fluidity of erythrocyte membranes, and on in vivo insulin sensitivity was studied in 6 non-insulin-dependent diabetic (NIDD) patients. An 8 weeks daily supplementation of 3 g of the omega 3 fatty acids eicosapentaenoic and docosahexaenoic acid resulted in an increase of the membrane phospholipid unsaturation and the sphingomyelin content. Erythrocyte membrane fluidity, measured with electron spin resonance of intact erythrocytes and with fluorescence polarization of erythrocyte ghosts, did not change. The in vivo insulin stimulated glucose uptake was estimated by determining the metabolic clearance rate (MCR) of glucose in the steady state of a simultaneous infusion during 150 min of glucose (33 mumol/kg/min) and insulin (50 mU/kg/hr). The MCR of glucose increased in all patients; from 3.93 +/- 0.55 - 4.69 +/- 0.74 ml/kg/min (mean +/- SEM, p less than 0.05). Plasma triglyceride concentrations fell from 1.9 +/- 0.3 - 1.2 +/- 0.2 mmol/l (mean +/- SEM, p less than 0.05). We conclude that in NIDDs dietary supplementation of omega 3 fatty acids improves in vivo insulin sensitivity and lowers plasma triglyceride levels, while erythrocyte membrane fluidity remains unaltered.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Female; Humans; Insulin; Linoleic Acid; Linoleic Acids; Male; Membrane Fluidity; Membrane Lipids; Middle Aged; Receptor, Insulin; Triglycerides

We measured the platelet total phospholipid fatty acid profiles of 20 insulin treated (Type I) diabetics, 20 non-insulin treated (Type II) diabetics and 20 matched non-diabetic controls to determine the relationship between the omega 6 and omega 3 series of fatty acids in diabetes. A significant inverse correlation between linoleic acid and arachidonic acid occurred in the normal subjects (r = -0.61; P less than 0.001) but was not seen in the Type I diabetics (r = -0.13; P = NS) or in the Type II diabetics (r = -0.27; P = NS). No significant correlation was seen between linolenic acid and eicosapentaenoic acid in the normal controls (r = -0.34; P = NS) or in the Type I diabetics (r = 0.21; P = NS) or in the Type II diabetics (r = -0.20; P = NS). The results suggest that a functional impairment of platelet delta 5 and delta 6 desaturase may occur in diabetes which disrupts the normal equilibrium between linoleic acid and arachidonic acid. However, the level of eicosapentaenoic acid appears to be less dependent on conversion from linolenic acid. Our findings are of importance to studies designed to reduce platelet aggregation in diabetics and non-diabetics by manipulation of the levels of the precursor fatty acids of thromboxane.

Topics: Adult; Arachidonic Acid; Arachidonic Acids; Blood Platelets; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Eicosapentaenoic Acid; Fatty Acid Desaturases; Humans; Insulin; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Platelet Aggregation; Thromboxanes