linoleic-acid and Diabetes-Mellitus--Type-1

Topics: Animal Feed; Animals; Chromatography, Gas; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 1; Humans; Isomerism; Linoleic Acid; Meat; Neoplasms; Safety

Topics: Adolescent; Arteriosclerosis; Blood Pressure; Child; Cholesterol; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diet, Sodium-Restricted; Dietary Fats; Energy Intake; Female; Humans; Hypertension; Linoleic Acid; Linoleic Acids; Lipoproteins; Male; Sodium

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 TaqIB cholesteryl ester transfer protein (CETP) gene polymorphism (B1B2) is a determinant of HDL cholesterol in nondiabetic populations. Remarkably, this gene effect appears to be modified by environmental factors. We evaluated the effect of this polymorphism on HDL cholesterol levels and on the lipoprotein response to a linoleic acid-enriched, low-cholesterol diet in patients with type 1 diabetes. In 44 consecutive type 1 diabetic patients (35 men), CETP polymorphism, apolipoprotein (apo) E genotype, serum lipoproteins, serum CETP activity (measured with an exogenous substrate assay, n = 30), clinical variables, and a diet history were documented. The 1-year response to diet was assessed in 14 type 1 diabetic patients, including 6 B1B1 and 6 B1B2 individuals. HDL cholesterol was higher in 10 B2B2 than in 14 B1B1 homozygotes (1.63 +/- 0.38 vs. 1.24 +/- 0.23 mmol/l, P < 0.01). HDL cholesterol, adjusted for triglycerides and smoking, was 0.19 mmol/l higher for each B2 allele present. CETP activity levels were not significantly different between CETP genotypes. Multiple regression analysis showed that VLDL + LDL cholesterol was associated with dietary polyunsaturated:saturated fatty acids ratio (P < 0.02) and total fat intake (P < 0.05) in the B1B1 homozygotes only and tended to be related to the presence of the apo E4 allele (P < 0.10). In response to diet, VLDL + LDL cholesterol fell (P < 0.05) and HDL cholesterol remained unchanged in 6 B1B1 homozygotes. In contrast, VLDL + LDL cholesterol was unaltered and HDL cholesterol decreased (P < 0.05) in 6 B1B2 heterozygotes (P < 0.05 for difference in change in VLDL + LDL/HDL cholesterol ratio). This difference in response was unrelated to the apo E genotype. Thus, the TaqIB CETP gene polymorphism is a strong determinant of HDL cholesterol in type 1 diabetes. This gene effect is unlikely to be explained by a major influence on the serum level of CETP activity, as an indirect measure of CETP mass. Our preliminary data suggest that this polymorphism may be a marker of the lipoprotein response to dietary intervention.

Topics: Adult; Alleles; Apolipoprotein A-I; Carrier Proteins; Cholesterol Ester Transfer Proteins; Cholesterol, Dietary; Cholesterol, HDL; Diabetes Mellitus, Type 1; Dietary Fats, Unsaturated; Female; Glycoproteins; Heterozygote; Homozygote; Humans; Linoleic Acid; Lipoproteins; Male; Middle Aged; Polymorphism, Genetic; Smoking; Triglycerides

We conducted a 2-year prospective randomised study to investigate the effects of a linoleic-acid-enriched diet on albuminuria and lipid levels in Type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion (overnight urinary albumin excretion rate between 10 and 200 micrograms/min). Thirty-eight patients were randomly assigned to increase dietary polyunsaturated:saturated fatty acids ratio to 1.0 by replacement of saturated fat with linoleic-acid-rich products (n = 18, two dropouts, analysis was performed in n = 16) or to continue their usual diet (n = 20). The total fat and protein content of the diet was unaltered. Clinical characteristics, albuminuria, blood pressure, glomerular filtration rate, metabolic control and dietary composition were similar in the two groups at baseline. In the high linoleic acid diet group, linoleic intake rose from 7 +/- 4 to 11 +/- 2 energy % and polyunsaturated:saturated fatty acids ratio rose from 0.60 +/- 0.28 to 0.96 +/- 0.16 (p less than 0.001 compared to usual diet group). The median increase albuminuria was 58% (95% confidence interval, 13 to 109) during the first year (p less than 0.02) and 55% (95% confidence interval, 11 to 127) (p less than 0.01) during the second year. Glomerular filtration rate remained unaltered and filtration fraction tended to rise (p less than 0.05 compared to usual diet group). In the usual diet group, albuminuria did not significantly increased by 16% (95% confidence interval, -17 to 38) and glomerular filtration rate declined during the second year. Blood pressure tended to rise similarly in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Albuminuria; Blood Pressure; Body Weight; Diabetes Mellitus, Type 1; Diet, Diabetic; Dietary Fats; Female; Glomerular Filtration Rate; Humans; Linoleic Acid; Linoleic Acids; Lipids; Lipoproteins; Male; Prospective Studies; Regression Analysis; Renal Circulation

Lisofylline (LSF) is an anti-inflammatory molecule with high aqueous solubility and rapid metabolic interconversion to its parent drug, pentoxifylline (PTX) resulting in very poor pharmacokinetic (PK) parameters, necessitating high dose and dosing frequency. In the present study, we resolved the physicochemical and pharmacokinetic limitations associated with LSF and designed its oral dosage form as a tablet for effective treatment in type 1 diabetes (T1D). Self-assembling polymeric micelles of LSF (lisofylline-linoleic acid polymeric micelles (LSF-LA PLM)) were optimized for scale-up (6 g batch size) and lyophilized followed by compression into tablets. Powder blend and tablets were evaluated as per USP. LSF-LA PLM tablet so formed was evaluated for in vitro release in simulated biological fluids (with enzymes) and for cell viability in MIN-6 cells. LSF-LA PLM in tablet formulation was further evaluated for intestinal permeability (in situ) along with LSF and LSF-LA self-assembled micelles (SM) as controls in a rat model using single-pass intestinal perfusion (SPIP) study. SPIP studies revealed 1.8-fold higher oral absorption of LSF-LA from LSF-LA PLM as compared to LSF-LA SM and ~5.9-fold higher than LSF (alone) solution. Pharmacokinetic studies of LSF-LA PLM tablet showed greater C

Topics: Administration, Oral; Animals; Cell Line; Cell Survival; Diabetes Mellitus, Type 1; Dosage Forms; Jejunum; Linoleic Acid; Male; Mice; Nanoparticles; Pentoxifylline; Perfusion; Rats; Rats, Wistar; Tablets

Oxylipins are lipid mediators derived from polyunsaturated fatty acids. Some oxylipins are proinflammatory (e.g. those derived from arachidonic acid [ARA]), others are pro-resolving of inflammation (e.g. those derived from α-linolenic acid [ALA], docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) and others may be both (e.g. those derived from linoleic acid [LA]). The goal of this study was to examine whether oxylipins are associated with incident type 1 diabetes.. We conducted a nested case-control analysis in the Diabetes Autoimmunity Study in the Young (DAISY), a prospective cohort study of children at risk of type 1 diabetes. Plasma levels of 14 ARA-derived oxylipins, ten LA-derived oxylipins, six ALA-derived oxylipins, four DHA-derived oxylipins and two EPA-related oxylipins were measured by ultra-HPLC-MS/MS at multiple timepoints related to autoantibody seroconversion in 72 type 1 diabetes cases and 71 control participants, which were frequency matched on age at autoantibody seroconversion (of the case), ethnicity and sample availability. Linear mixed models were used to obtain an age-adjusted mean of each oxylipin prior to type 1 diabetes. Age-adjusted mean oxylipins were tested for association with type 1 diabetes using logistic regression, adjusting for the high risk HLA genotype HLA-DR3/4,DQB1*0302. We also performed principal component analysis of the oxylipins and tested principal components (PCs) for association with type 1 diabetes. Finally, to investigate potential critical timepoints, we examined the association of oxylipins measured before and after autoantibody seroconversion (of the cases) using PCs of the oxylipins at those visits.. The ARA-related oxylipin 5-HETE was associated with increased type 1 diabetes risk. Five LA-related oxylipins, two ALA-related oxylipins and one DHA-related oxylipin were associated with decreased type 1 diabetes risk. A profile of elevated LA- and ALA-related oxylipins (PC1) was associated with decreased type 1 diabetes risk (OR 0.61; 95% CI 0.40, 0.94). A profile of elevated ARA-related oxylipins (PC2) was associated with increased diabetes risk (OR 1.53; 95% CI 1.03, 2.29). A critical timepoint analysis showed type 1 diabetes was associated with a high ARA-related oxylipin profile at post-autoantibody-seroconversion but not pre-seroconversion.. The protective association of higher LA- and ALA-related oxylipins demonstrates the importance of both inflammation promotion and resolution in type 1 diabetes. Proinflammatory ARA-related oxylipins may play an important role once the autoimmune process has begun.

Topics: Adolescent; Arachidonic Acid; Autoantibodies; Autoimmunity; Case-Control Studies; Child; Child, Preschool; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 1; Docosahexaenoic Acids; Female; Follow-Up Studies; Glutamate Decarboxylase; HLA-DR3 Antigen; HLA-DR4 Antigen; Humans; Insulin; Linoleic Acid; Male; Oxylipins; Prospective Studies; Receptor-Like Protein Tyrosine Phosphatases, Class 8; Tandem Mass Spectrometry

Plasma fatty acids (FAs) and micronutrients have been associated with central obesity in adults; however, previous studies of these associations in adults have yielded mixed results. In addition, no comparable research has been conducted among youth with type 1 diabetes (T1D).. We investigated the cross-sectional and longitudinal associations between plasma nutrient biomarkers and waist-to-height ratio (WHtR) in youth with T1D.. These analyses included 1324 youth aged 3-20 y at T1D diagnosis with a baseline visit in the SEARCH (Search for Diabetes in Youth) Study and a subset of 1178 of these youth with a follow-up visit an average of 23 mo (range: 16-40 mo) after their baseline visit. Plasma phospholipid FAs and vitamins were measured, and estimated desaturase activities were calculated at baseline. Anthropometric measurements and diabetes-related assessments were collected at each visit. Multiple linear regression was used to examine the association between plasma nutrient biomarkers and WHtR.. In cross-sectional analysis, plasma palmitic acid (P = 0.004), dihomo-γ-linolenic acid (DGLA; P = 0.017) and Δ6 desaturase (D6D; P = 0.006) were positively correlated with WHtR after adjustment of confounders. Oleic acid (OA; P = 0.002), linoleic acid (LA; P = 0.015), Δ9 desaturase 18 (D9D-18; P = 0.027), and vitamin D (P < 0.0001) were negatively correlated with WHtR after adjustment. Weight status was an effect modifier (P < 0.05). In normal-weight youth, vitamin D (P = 0.003) was negatively associated with WHtR. In obese youth, stearic acid (P = 0.037), DGLA (P < 0.0001), and D6D (P < 0.0001) were positively associated and OA (P = 0.0008), D9D-18 (P = 0.0006), and vitamin D (P < 0.0001) were negatively associated with WHtR. In longitudinal analysis, baseline linoleic acid (P = 0.018), n-6:n-3 (ω-3:ω-6) FA ratio (P = 0.029), vitamin D (P = 0.003), and vitamin E (P < 0.0001) were negatively correlated with WHtR at follow-up only in obese participants.. In T1D youth, plasma FAs and vitamins are associated with WHtR and are modified by weight status. These associations are particularly marked in obese youth.

Topics: Adolescent; Biomarkers; Body Height; Body Mass Index; Body Weight; Child; Child, Preschool; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Fatty Acid Desaturases; Fatty Acids, Omega-3; Female; Follow-Up Studies; Humans; Limit of Detection; Linoleic Acid; Longitudinal Studies; Male; Micronutrients; Obesity; Palmitic Acid; Phospholipids; Prospective Studies; Vitamin D; Vitamin E; Waist Circumference; Young Adult

Streptozotocin (STZ)-induced diabetes in mice progresses with decreased desaturase activities and alterations in the metabolism of essential fatty acids (EFA).. Based on our previous studies with soybean oil that ameliorated the STZ damage in mice, we tested here the accountability of its main EFA components, i.e. linoleic acid (LA) and alpha linolenic acid (ALA), in the prevention of pancreas damage and Δ6 desaturase decrease.. Seven days after injection with STZ and EFA gavage, ICR mice were sacrificed. Plasma glucose and insulin levels, pancreas histology and liver fatty acid desaturases were analysed.. EFA reduced pancreas damage, insulin and glucose plasma levels and restored Δ6 desaturase activity and mRNA expression levels.. By reducing pancreas damage, EFA ameliorated insulin levels, Δ6 desaturase and fatty acid metabolism. LA further enhanced Fads2 promoter activity.. EFA ameliorate STZ induced diabetes in mice.

Topics: alpha-Linolenic Acid; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diet; Hep G2 Cells; Humans; Linoleic Acid; Linoleoyl-CoA Desaturase; Male; Mice; Mice, Inbred ICR

Hypoinsulinemia characteristic to type 1 diabetes may theoretically inhibit the conversion of essential fatty acids to their longer-chain metabolites. Fatty acids were determined in plasma and erythrocyte membrane lipids in young diabetic adults (n=34) and in age-matched healthy controls (n=36). Values of linoleic acid (56.01 [5.02] versus 51.05 [7.32], % by wt, median [range from the first to the third quartile], P<0.00l) and arachidonic acid (AA) (11.17 [2.98] versus 9.69 [1.95] P<0.001) were significantly higher in diabetic subjects than in controls. However, alpha-linolenic acid values did not differ, and docosahexaenoic acid (0.43 [0.12] versus 0.57 [0.29], P<0.01) values were significantly lower in diabetic than in control subjects. Significant inverse correlations were found between AA and hemoglobin A(1c) values in the phospholipid (r=-0.40, P<0.05) and sterol ester (r=-0.40, P<0.05) fractions. The data obtained in the present study suggest that the availability of n-3 long-chain polyunsaturated fatty acid may be reduced in young diabetic adults.

Topics: Adolescent; Adult; alpha-Linolenic Acid; Arachidonic Acid; Case-Control Studies; Diabetes Mellitus, Type 1; Docosahexaenoic Acids; Erythrocyte Membrane; Fatty Acids, Unsaturated; Female; Glycerylphosphorylcholine; Hemoglobin A; Humans; Linoleic Acid; Male; Membrane Lipids; Phosphatidylethanolamines; Phospholipids; Sterols

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

The effect of the apolipoprotein (apo) E genotype on the lipoprotein response to a 1 year low cholesterol diet (200 mg cholesterol per day) was evaluated in 36 patients with Type 1 diabetes mellitus with albuminuria between 10 and 200 microg min(-1). Apo E genotype was characterized by polymerase chain reaction and restriction isotyping. In 11 IDDM patients with at least one epsilon4 allele (apo E4 group), baseline serum total and low density lipoprotein (LDL) cholesterol were higher (p < 0.05 for both) than in 25 patients without an epsilon4 allele and with at least one epsilon3 allele (apo E3 group). Dietary counselling resulted in a similar decrease in cholesterol intake in both groups, whereas linoleic acid did not change. In the apo E4 group, serum total and LDL cholesterol at follow-up fell (p < 0.01 for both) to levels that were not different from those in the apo E3 group, and the changes in these parameters were greater (p < 0.02) than those in the apo E3 group. We conclude that the apo E4 allele is associated with atherogenic lipoprotein abnormalities in Type 1 DM patients with minor elevations in albuminuria when they use their habitual diet. Apo E4 carrying patients respond better to a low cholesterol diet.

Topics: Adult; Albuminuria; Alleles; Apolipoprotein A-I; Apolipoprotein E3; Apolipoprotein E4; Apolipoproteins B; Apolipoproteins E; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 1; Dietary Fats, Unsaturated; Female; Genotype; Glycated Hemoglobin; Humans; Linoleic Acid; Male; Polymerase Chain Reaction; Predictive Value of Tests

The incidence of obesity, noninsulin-dependent diabetes mellitus (NIDDM), hypertension, and coronary artery disease has increased in the developed world. At the same time, major changes in the type and amount of fatty acid intake have occurred over the past 40-50 years, reflected in increases in saturated fat (from both animal sources and hydrogenated vegetable sources), trans fatty acids, vegetable oils rich in linoleic acid, and an overall decrease in long chain polyunsaturated fatty acids (arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid--C20-C22). Recent findings that C20-C22 in muscle membrane phospholipids are inversely related to insulin resistance, whereas linoleic acid is positively related to insulin resistance, suggest that diet may influence the development of insulin resistance in obesity, insulin-dependent diabetes mellitus (IDDM), hypertension, and coronary artery disease (including asymptomatic atherosclerosis and microvascular angina). These conditions are known to have genetic determinants and have a common abnormality in smooth muscle response and insulin resistance. It is proposed that the current diet influences the expression of insulin resistance in those who are genetically predisposed. Therefore, clinical investigations are needed to evaluate if lowering or preventing insulin resistance through diet by increasing arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, while lowering linoleic acid and decreasing trans fatty acids from the diet, will modify or prevent the development of these diseases.

Topics: Animals; Coronary Disease; Diabetes Mellitus, Type 1; Dietary Fats; Fatty Acids; Fatty Acids, Unsaturated; Humans; Hypertension; Insulin Resistance; Linoleic Acid; Linoleic Acids; Models, Biological; Obesity; Vegetables

Diabetes mellitus is associated with a high incidence of cardiovascular diseases not directly attributable to hyperlipidemia, smoking, or hypertension, but which in part may be explained by an enhanced tendency to thrombosis due to increased platelet activity. The aim of this study was to evaluate platelet function and compare the effectiveness of the antiplatelet drug aspirin on platelet aggregation in diabetic and nondiabetic subjects. Platelet aggregation and composition were examined in 20 male insulin-dependent diabetes mellitus (IDDM) patients and 20 nondiabetic control subjects matched for age and body mass index. All were normotensive with serum total cholesterol less than 6.5 mM. Although within the clinically acceptable normal range, blood pressure was significantly higher in diabetic patients (130/75 mmHg) than in control subjects (123/70 mmHg) (P less than 0.05). Serum thromboxane B2 and ex vivo aggregation of platelets in response to two doses of the agonists collagen and platelet-activating factor (PAF) were similar to nondiabetic subjects. However, after taking 100 mg/day aspirin for 5 days, platelet aggregation to collagen was reduced by 76% in control subjects compared to 56% in IDDM patients (P less than 0.001). Aspirin treatment also reduced the slope of the aggregation curve and increased the lag time (the period between the addition of collagen and the start of irreversible aggregation) significantly more in control than in diabetic platelets. This difference in platelet aggregation could not be attributed to differences in platelet serotonin or thromboxane A2 secretion, the latter being almost completely suppressed by aspirin in each group. Platelet aggregation to PAF was similar in both groups and was not affected by aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aspirin; Blood Pressure; Cholesterol; Collagen; Diabetes Mellitus, Type 1; Fatty Acids, Omega-3; Humans; Linoleic Acid; Linoleic Acids; Male; Membrane Fluidity; Phospholipids; Platelet Activating Factor; Platelet Aggregation; Platelet Aggregation Inhibitors; Reference Values; Thromboxane B2

Binding equilibria of long-chain fatty acids to human serum albumin, in serum or plasma, were studied by a dialysis exchange rate technique. Palmitate was added to citrated plasma in vitro and it was observed that between six and ten palmitate molecules were bound to albumin with nearly equal affinity. Observations in vivo gave similar results in the following series: (a) in two volunteers with increased fatty acid concentrations after fasting, exercise, and a cold shower: (b) in three male volunteers in whom high concentrations of non-esterified fatty acids, up to 4.6 mM, were induced by intravenous administration of a preparation of lecithin/glycocholate mixed micelles, and (c) in 81 patients with diabetes mellitus, type I. The binding pattern of palmitate in serum or plasma is essentially different from that observed with palmitate added to buffered solutions of pure albumin when two molecules are tightly bound and about four additional molecules with lower affinity. The differences may partly be explained by the presence of chloride ions in blood plasma, reducing the affinity for binding of the first two fatty acid molecules, and partly by facilitated binding of several molecules of mixed fatty acids, as found in plasma.

Topics: Diabetes Mellitus, Type 1; Fatty Acids, Nonesterified; Humans; Kinetics; Linoleic Acid; Linoleic Acids; Micelles; Myristic Acid; Myristic Acids; Oleic Acid; Oleic Acids; Palmitic Acid; Palmitic Acids; Protein Binding; Reference Values; Serum Albumin

Free radicals are unstable chemical species which react with and oxidize adjacent molecules, particularly polyunsaturated lipids. The diene-conjugated non-peroxide isomer of linoleic acid (PL-9,11-LA') has been identified as the main diene-conjugated compound in plasma, and is a probable marker of free radical activity. The aim of the current study was to determine whether the level of PL-9,11-LA', measured by HPLC, is altered in insulin-dependent diabetes, and to investigate whether any abnormality demonstrated correlated with microvascular disease in the form of retinopathy. There was no difference in the concentrations of linoleic acid between the diabetic and control groups (422(129) vs 402(81) (SD) mumol l-1). However, the concentration of PL-9,11-LA' was significantly reduced in the diabetic group compared with control group (15.6(6.7) vs 19.3(3.9) mumol l-1, p less than 0.01), with the molar ratio of PL-9,11-LA':linoleic acid x 100 similarly reduced (3.8(1.3) vs 5.0(1.6)%, p less than 0.005). This study does not support the concept that free radicals play a significant role in the development of diabetic vascular disease.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Female; Free Radicals; Glycated Hemoglobin; Humans; Linoleic Acid; Linoleic Acids; Male; Reference Values

Fatty acids in erythrocyte membranes and plasma were determined by capillary gas-liquid chromatography in 27 controls and 44 subjects with insulin-dependent diabetes mellitus. Significant decreases in stearic acid (P less than 0.00003) and arachidonic acid (P less than 0.001) and significant increases in palmitic acid (P less than 0.00003) were observed in erythrocytes from diabetic patients. The stearic:oleic acid ratios and arachidonic:linoleic acid ratios in erythrocytes were significantly lower in diabetic patients than in controls (P less than 0.0003 and less than 0.0007, respectively). The relative concentration of palmitic acid in plasma (as a percentage of the sum of the five major fatty acids) was increased in diabetic patients, as compared with controls (P less than 0.0125). We observed no other significant differences in fatty acids in plasma, making it unlikely that changes in fatty acids in erythrocyte membranes in diabetic patients can be accounted for simply by alterations in the fatty acids in plasma. We propose that impaired metabolic control associated with diabetes mellitus may interfere with the maintenance of fatty acid profiles in erythrocyte membranes against the concentration gradients in plasma.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arachidonic Acid; Arachidonic Acids; Blood Glucose; Chromatography, Gas; Diabetes Mellitus, Type 1; Erythrocyte Membrane; Fatty Acids; Female; Glycated Hemoglobin; Humans; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Oleic Acid; Oleic Acids; Palmitic Acid; Palmitic Acids; Stearic Acids

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

Hypertensive patients had higher levels of linoleic acid (LA) in serum lipids than normal controls. Administration of large doses of LA failed to raise the percentage of its metabolite arachidonic acid (AA) in serum lipids. Similarly, intake of large amounts of alpha-linolenic acid (alpha-LNA) failed to increase the amount of eicosapentaenoic acid (EPA). The percentage of EPA in serum lipids could readily be increased by direct administration of comparably low doses in a mackerel diet. Hypertensive subjects seem to desaturate and elongate LA and alpha-LNA only very slowly.

Topics: Animals; Cholesterol Esters; Diabetes Mellitus, Type 1; Dietary Fats; Fatty Acids, Unsaturated; Fishes; Humans; Hypertension; Linoleic Acid; Linoleic Acids; Linseed Oil; Male; Meat; Oils; Plant Oils; Reference Values; Sunflower Oil; Triglycerides

Platelet function, estimated from plasma beta-thromboglobulin (beta-TG, ng/ml), is frequently altered in insulin-dependent diabetics (IDDs). As several factors may affect beta-TG, we studied respectively in 15 IDDs, the roles played by: (i) diabetic control evaluated from glycosylated haemoglobin (HbA1); (ii) plasma C-peptide and pancreatic glucagon; (iii) plasma lipids and the relative percentages of fatty acids in total plasma lipids. Plasma beta-TG did not correlate significantly with the first 3 parameters. However, beta-TG was correlated: (i) positively with plasma triglycerides (P less than 0.01), cholesterol (P less than 0.02), phospholipids (P less than 0.05) and total plasma lipids (P less than 0.01) and the percentage of oleic acid (C18 : 1 omega 9) in plasma lipids (P less than 0.01); (ii) negatively with the percentage of linoleic acid (C18 : 2 omega 6) in plasma lipids (P less than 0.02). No correlation was found between beta-TG and the percentages of the other saturated (C16 : 0, C18 : 0), monounsaturated (C16 : 1 omega 7) and polyunsaturated fatty acids (C18 : 3 omega 6, C20 : 3 omega 6 and C20 : 4 omega 6). The present results indicate that beta-TG in IDDs can be markedly improved by all dietary and therapeutic measures which lower plasma lipids and increase the percentage of the linoleic acid in the body.

Topics: Adult; Aged; beta-Thromboglobulin; Blood Platelets; Cholesterol; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Fatty Acids; Female; Humans; Linoleic Acid; Linoleic Acids; Lipids; Male; Middle Aged; Oleic Acid; Oleic Acids; Phospholipids; Triglycerides