Relationship between n-3 and n-6 plasma fatty acid levels and insulin resistance in coronary patients with and without metabolic syndrome

Background and aimsAnimal studies show that ecosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are effective for the prevention and treatment of insulin resistance (IR). Data from human studies are contradictory. We sought to determine whether the relationships between plasma n-3 and n-6 polyunsaturated fatty acid (FA) levels and IR differ according to the presence or absence of metabolic syndrome (MS) in a coronary heart disease sample.Method and resultsClinical, metabolic parameters, plasma phospholipid FA profiles and indirect measurement of IR (homeostatic model assessment-HOMA) were measured in 734 subjects, 8 weeks following acute coronary syndrome. FA levels and their correlations with IR were compared in subjects with and without MS. MS patients had higher saturated (16:0, 18:0) and n-6 (18:3n-6, 20:3n-6, 22:4n-6, 22:5n-6) FA levels, and lower EPA and DHA levels. HOMA-IR correlated positively with total saturated (r = 0.13, P = 0.017) and n-6 (r = 0.17, P = 0.001) FA levels and negatively with total n-3 FA levels (r = −0.13, P = 0.012), in MS subjects only. Total n-3 and n-6 FAs and n-6/n-3 ratio were associated with HOMA-IR levels in MS subjects independent of total saturated FA levels, age, sex, sedentary behaviour, smoking, waist circumference, triglycerides, HDL-cholesterol, and systolic blood pressure.ConclusionsRelationships between polyunsaturated FA type and IR vary according to the presence or absence of MS. N-3 FAs including EPA and DHA are associated with lower HOMA-IR, while the opposite is true for n-6 FAs. Prospective studies are required to address the potential effects of intermediate dose EPA and DHA on glucose handling in MS patients.     

Relationship of serum fatty acid composition and desaturase activity to C-reactive protein in Japanese men and women

BackgroundAlthough fatty acid composition in serum and desaturase activity, which alters serum fatty acid composition, has been associated with C-reactive protein (CRP) concentration in Western populations, no study has been carried out in non-Western populations. We examined the association of serum fatty acids and estimated desaturase activity with CRP concentrations in Japanese men and women.MethodsSubjects were 489 Japanese municipal employees aged 21–67 years who participated in a survey at the time of a periodic health check-up. Serum high-sensitivity CRP concentrations were measured using the latex agglutination nephelometry method. Fatty acid composition was measured in serum cholesteryl esters and desaturase activities by fatty acid product-to-precursor ratios. Relationships were assessed using multiple regression.ResultsSerum CRP concentration was positively associated with palmitic acid (P for trend = 0.002) and inversely with alpha-linolenic acid (P for trend = 0.01) in men, and positively with dihomo-gamma-linolenic acid (P for trend in men or women = 0.01) and inversely with delta-5-desaturase (20:4n-6/20:3n-6) (P for trend in men and women = 0.05 and 0.002, respectively) in men and women.ConclusionsLow-grade inflammation may be associated with a serum fatty acid pattern of high palmitic acid or low alpha-linolenic acid in men, and of high dihomo-gamma-linolenic acid or low delta-5-desaturase in both sexes.     

Effects of soybean D-LeciVita product on serum lipids and fatty acid composition in type 2 diabetic patients with hyperlipidemia

Background and aimHyperlipidemia is one of the major risk factors of cardiovascular complication in diabetes. High intake of soy product has been suggested to prevent cardiovascular disease. The purpose of this study was to evaluate if dietary supplement of soybean D-LeciVita product, rich in polyunsaturated phospholipids (with 12% lecithin, 35% soy protein) affects serum lipids and serum and erythrocyte phospholipid fatty acid composition in type 2 diabetic patients.Methods and resultsForty-seven patients (men and post-menopausal women) with isolated hypertriglyceridemia (IHTG) and combined hyperlipidemia (CHL), aged 43–70 years, were given 15 g of D-LeciVita powder as a water suspension in a single evening dose during the follow-up period of 12 weeks. Patients kept their diabetic diet relatively constant. Treatment was associated with a significant (p ≤ 0.001) decrease in serum total cholesterol and triglyceride levels by 12% and 22%, respectively. LDL-cholesterol decreased by 16% and HDL-cholesterol increased by 11% (p ≤ 0.001). Our study shows a 27% decrease in LDL-cholesterol (p ≤ 0.001) and a 12% increase in HDL-cholesterol (p ≤ 0.01) in CHL type 2 diabetic patients. Triglyceride levels decreased in type 2 diabetic patients with IHTG and CHL by 29% and 13%, respectively (p ≤ 0.01 and p ≤ 0.05). Our results show decrease in SFA and increase in n-6 and n-3 PUFA in serum and erythrocyte phospholipids. SFA decreased and n-3 PUFA increased in serum and erythrocyte phospholipids in IHTG and CHL groups.ConclusionThe present study indicated that added to a regular diet, soybean D-LeciVita product (combination of soy protein and lecithin) is associated not only with lipid-lowering effects but also with more favorable serum phospholipids fatty acid profile in type 2 diabetic patients with hyperlipidemia.     

Dietary fatty acids and peripheral artery disease in adults

BackgroundPeripheral artery disease (PAD) is a debilitating condition involving atherosclerosis. Although saturated, monounsaturated and polyunsaturated fatty acids have strong associations with atherosclerosis, it is unclear if diets high in these fatty acids affect PAD.MethodsWe studied 6352 adults aged 40 years and older who participated in the U.S. National Health and Nutrition Examination Survey between 1999 and 2004. Ankle brachial index (ABI) was assessed by standardized blood pressure measurements, and we defined PAD as an ABI < 0.9. Fatty acid intake was assessed by validated 24-h dietary recall. We used multivariable linear and logistic regression to estimate associations between intakes of dietary saturated fatty acids (SFAs), monounsaturated fatty acids (MFAs), marine omega-3 fatty acids (N-3), linolenic acid (LNA), and omega-6 fatty acids (N-6) and ABI/PAD.ResultsThe prevalence and 95% confidence interval (CI) of PAD was 5.2% (95% CI 4.6–5.8).There were no associations between ABI and intakes of marine N-3 (p = 0.83) or N-6 (p = 0.19) in adjusted models. In contrast, LNA was associated with higher ABI (p = 0.04) and SFA tended to be associated with lower ABI (p = 0.06) in adjusted models. In addition, higher SFA was associated with a higher prevalence of PAD: adjusted odds ratio 1.30 (95% CI 1.01–1.67; p = 0.04) and a trend toward slower gait speed (p = 0.08).ConclusionIn this nationally representative sample, higher dietary intakes of LNA and SFAs were associated with higher and lower ABI, respectively. Prospective studies are needed to confirm the potential protective effects of dietary LNA and detrimental effects of dietary SFAs on PAD.     

Influence of n-3 polyunsaturated fatty acids on soluble cellular adhesion molecules as biomarkers of cardiovascular risk in young healthy subjects

Background and aimSerum levels of soluble cellular adhesion molecules (CAMs) and blood lipid parameters have been used as markers of inflammatory processes associated with cardiovascular disease (CVD) events. The present study evaluated the effects of the intake of n-3 polyunsaturated fatty acids (PUFAs) in fish and fish oil within energy-restricted diets, on soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1).Methods and resultsTwo hundred and seventy-five healthy European subjects aged between 20 and 40 years, were randomized to one of four hypocaloric dietary groups: control (sunflower oil capsules, no seafood), lean fish (3 × 150 g portions of cod/week), fatty fish (3 × 150 g portions of salmon/week), fish oil ((docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) capsules, no seafood)). Diets rich in lean fish significantly decreased ICAM-1 levels, around 5% from baseline to endpoint (p < 0.05), and had no effect on VCAM-1 levels. No significant differences were observed in sICAM-1 levels after the intervention with fatty fish or fish oils. On the other hand, these two seafood based diets were responsible for a significant increase of VCAM-1 levels [fatty fish; 16.1% and fish oil; 21.9%] respectively (p < 0.05).ConclusionsCAMs as inflammatory biomarkers in young and healthy subjects are not conclusive for the evaluation of CVD risk. Hypocaloric fish diets had a different effect on CAMs, being lean fish responsible for the highest decrease in ICAM-1. On the other hand, VCAM-1 results allow speculation that a low dose of n-3 PUFA may be anti-inflammatory contrarily to a high dose which can have a pro-inflammatory effect. CAMs mechanism is complex and affected by multiple factors such as lifestyle, gender, and n-3 dose and source.     

Levels of the n-3 fatty acid eicosapentaenoic acid in addition to those of alpha linolenic acid are significantly raised in blood lipids by the intake of four walnuts a day in humans

Background and aimsIngestion of alpha linolenic acid (ALA), with the richest source among dry fruits such as walnuts, is associated with cardiovascular prevention. The aim of this study was to selectively evaluate the effects of moderate walnut consumption on the levels of ALA and its metabolic derivatives in human blood.Methods and resultsAfter a 2-week run-in period, 10 volunteers consumed 4 walnuts per day (in addition to their habitual diet) for 3 weeks. Fatty acid profiles, with special attention to levels of ALA and long chain polyunsaturated fatty acids (LC-PUFA), were assessed in blood drops collected from fingertips. The data indicate that the administration of a few walnuts a day for 3 weeks significantly increases blood levels, not only of ALA (from 0.23 ± 0.07 SD to 0.47 ± 0.13 SD), but also of its longer chain derivative eicosapentaenoic acids (EPA) (from 0.23 ± 0.37 to 0.82 ± 0.41) with levels remaining elevated over basal values after washout.ConclusionThe findings of this pilot study indicate that plant ALA in appropriate food items favourably affects the n-3 LC-PUFA status.     

Improvement of the omega 3 index of healthy subjects does not alter the effects of dietary saturated fats or n-6PUFA on LDL profiles

Background and AimsDietary fat composition is known to modulate circulating lipid and lipoprotein levels. Although supplementation with long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) has been shown to reduce plasma triglyceride levels, the effect of the interactions between LCn-3PUFA and the major dietary fats consumed has not been previously investigated.MethodsIn a randomized controlled parallel design clinical intervention, we examined the effect of diets rich in either saturated fatty acids (SFA) or omega-6 polyunsaturated fatty acids (n-6PUFA) on plasma lipid levels and lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) in subjects with an adequate omega 3 index. Twenty six healthy subjects went through a four-week pre-supplementation period with LCn-3PUFA and were then randomized to diets rich in either n-6PUFA or SFA both supplemented with LCn-3PUFA.ResultsThe diet rich in n-6PUFA decreased low density lipoprotein (LDL) particle concentration (− 8%, p = 0.013) and LDL cholesterol (LDL-C) level (− 8%, p = 0.021), while the saturated fat rich diet did not affect LDL particle concentration or LDL-C levels significantly. Nevertheless, dietary saturated fatty acids increased LCn-3PUFA in plasma and tissue lipids compared with n-6PUFA, potentially reducing other cardiovascular risk factors such as inflammation and clotting tendency.ConclusionImprovement on the omega 3 index of healthy subjects did not alter the known effects of dietary saturated fats and n-6PUFA on LDL profiles.     

FADS gene polymorphisms in Koreans: association with ω6 polyunsaturated fatty acids in serum phospholipids, lipid peroxides, and coronary artery disease

ObjectiveWe investigated the association of polymorphisms in FADS genes with polyunsaturated fatty acids (PUFAs) in serum phospholipids, lipid peroxides, and coronary artery disease (CAD) in Koreans.MethodsIn this case–control study, CAD patients (n = 756, 40–79 years) and healthy controls (n = 890) were genotyped for rs174537 near FADS1 (FEN1 rs174537G > T), FADS2 (rs174575, rs2727270), and FADS3 (rs1000778). We calculated the odds ratios (ORs) for CAD risk and measured serum PUFA composition and lipid peroxide.ResultsAmong four SNPs, only rs174537G > T differed in allele frequencies between controls and CAD patients after adjustment for age, BMI, cigarette smoking, alcohol consumption, hypertension, diabetes mellitus, and hyperlipidemia (P = 0.017). The minor T allele was associated with a lower risk of CAD [OR 0.75 (95%CI 0.61–0.92), P = 0.006] after adjustment. rs174537T carriers had a significantly higher proportion of linoleic acid (LA, 18:2ω6), lower arachidonic acid (AA, 20:4ω6), and lower ratios of AA/dihomo-γ-linolenic acid (DGLA, 20:3ω6) and AA/LA than G/G subjects in both control and CAD groups. In the control group, 174537T carriers had significantly lower levels of total- and LDL-cholesterol, malondialdehyde, and ox-LDL. In CAD patients, rs174537T carriers showed a larger LDL particle size than G/G subjects. The proportion of AA in serum phospholipids positively correlated with LDL-cholesterol, ox-LDL, and malondialdehyde in controls and with 8-epi-prostaglandin F_2α in both control and CAD groups.ConclusionThe rs174537T is associated with a lower proportion of AA in serum phospholipids and reduced CAD risk, in association with reduced total- and LDL-cholesterol and lipid peroxides.     

Biomarkers of dairy intake and the risk of heart disease

Background and aimsDespite their relatively high content of saturated fat, studies of dairy product intake and the risk of cardiovascular disease have often yielded null or inverse results. The use of fatty acid biomarkers to reflect dairy intake could elucidate this association. This study aims to evaluate the association between dairy intake, assessed by adipose pentadecanoic (15:0) and heptadecanoic (17:0) fatty acids and food frequency questionnaire (FFQ), and the risk of nonfatal myocardial infarction (MI), in a matched case-control study of Costa Rican adults (n = 3630).Methods and resultsThe association was examined using conditional logistic regression, adjusted for potential confounders. The associations of adipose tissue 15:0 and 17:0 with the risk of MI were not statistically significant (for 15:0: multivariate-adjusted OR for 5th quintile vs. 1st = 1.14 (95% CI = 0.85, 1.53), p-value for linear trend = 0.77; for 17:0: multivariate-adjusted OR for 5th quintile vs. 1st = 1.15 (95% CI = 0.88, 1.51), p-value for linear trend = 0.18). The association between the FFQ measure of dairy intake and MI showed evidence of a possible threshold effect, with a protective association observed for all but the top quintile of the exposure distribution.ConclusionDairy product intake as assessed by adipose tissue 15:0, 17:0, and by FFQ is not associated with a linear increase in the risk of MI in the study population. It is possible that the adverse effect of saturated fat in dairy products on cardiovascular health is offset by presence of beneficial nutrients.     

Subgram daily supplementation with docosahexaenoic acid protects low-density lipoproteins from oxidation in healthy men

ObjectiveTo determine the effect of supplementation with increasing doses of docosahexaenoic acid (DHA), as the only n-3 polyunsaturated fatty acid (PUFA), on low-density lipoprotein (LDL) redox status and oxidizability.MethodsTwelve healthy men aged 53–65 years ingested consecutive doses of DHA (200, 400, 800 and 1600 mg/day), each dose for two weeks.ResultsThe proportions of DHA increased dose-dependently in LDL phospholipids and cholesteryl esters, even after two weeks of supplementation with 200 mg/day DHA. The daily intake of 200, 400 and 800 mg DHA resulted in increased alpha-tocopherol concentrations, decreased MDA concentrations, and a longer lag time for copper-induced LDL oxidation. Supplementation with 1600 mg/day DHA had no effect on the above parameters. In plasma, concentrations of 4-hydroxy-hexenal, specifically derived from the peroxidation of n-3 fatty acids, significanty increased after 800 and 1600 mg DHA, representing 0.01% of plasma n-3 PUFAs, while 4-hydroxy-nonenal concentrations, derived from the peroxidation of n-6 fatty acids, did not change.ConclusionOur results clearly show that an intake of 200–800 mg/day DHA may have protective and antioxidant effects on LDL and could represent optimal doses for cardiovascular disease prevention in a healthy population.     

The effect of pioglitazone as add-on therapy to metformin or sulphonylurea compared to a fixed-dose combination of metformin and glibenclamide on diabetic dyslipidaemia

Background and aimsDiabetic dyslipidaemia contributes to the increased risk of cardiovascular disease in patients with Type 2 diabetes. This paper examines the effectiveness of adding pioglitazone to metformin or a sulphonylurea (SU) compared with a fixed-dose combination of metformin and glibenclamide on diabetic dyslipidaemia in patients with Type 2 diabetes.Methods and resultsPatients (n = 250) treated with metformin (≤3 g/day) or an SU as monotherapy at a stable dose for ≥3 months were randomised to receive either pioglitazone (15–30 mg/day) in addition to their metformin or SU, or a fixed-dose combination tablet containing metformin (400 mg) and glibenclamide (2.5 mg) [up to 3 tablets daily] for 6 months. Addition of pioglitazone tended to increase plasma high-density lipoprotein-cholesterol (HDL-C) [0.04 mmol/L; P = 0.051] at 6 months and significantly reduced plasma triglycerides (−0.25 mmol/L; P = 0.013) compared with baseline. Patients treated with metformin/glibenclamide for 6 months had reduced HDL-C (−0.09 mmol/L; P < 0.01) and no change in plasma triglyceride levels (0.03 mmol/L; P = 0.733). Both treatment regimes resulted in a similar level of glycaemic control.ConclusionThe beneficial effects of pioglitazone on diabetic dyslipidaemia may help combat the increased cardiovascular morbidity and mortality observed in patients with Type 2 diabetes while providing stable glycaemic control.     

Body mass interacts with fat quality to determine the postprandial lipoprotein response in healthy young adults

Background and aimsPostprandial lipemia predicts the evolution of cardiovascular disease. Obesity is associated with an increase in the magnitude of postprandial lipemia. Our objective was to evaluate the influence of body mass index (BMI) on the effects of acute ingestion of different types of fat on the postprandial lipemic response.Methods and resultsTwenty-one healthy men followed a 4-week baseline diet and then consumed three fat-loaded meals that included 1 g fat/kg body wt (65%fat) according to a randomized crossover design. The compositions of the three meals were olive oil meal (22% saturated fatty acids (SFA), 38% monounsaturated fatty acids (MUFA), 4% polyunsaturated fatty acids (PUFA)); butter meal (35% SFA, 22% MUFA, 4% PUFA); walnuts meal (20% SFA, 24% MUFA, 16% PUFA, and 4% α-linolenic acid). Higher-weight (HW) subjects (BMI greater than the median 26.18 kg/m², n = 11) presented higher incremental area under the curve (iAUC) for triglycerides (TG), both in large- and small-TG rich lipoproteins (TRL) than lower-weight (LW) subjects (BMI < 26.18 kg/m², n = 10) (p < 0.05), and a similar trend for plasma TG (p = 0.084). Moreover, HW subjects presented higher concentrations for small TRL-cholesterol and small TRL-TG in different timepoints of the postprandial lipemia after the intake of enriched walnuts or butter meals compared with the olive oil-enriched meal (p < 0.05) No significant differences were observed between the three types of meals in the postprandial response of LW subjects.ConclusionHW subjects present a greater postprandial response than LW subjects, and they benefit from the consumption of monounsaturated fatty acids from olive oil, to lower their levels of TRL particles during the postprandial state.     

Altered colonic mucosal availability of n-3 and n-6 polyunsaturated fatty acids in ulcerative colitis and the relationship to disease activity

Background and AimsThe polyunsaturated fatty acids (PUFA) arachidonic acid (AA, n-6) and eicosapentaenoic acid (EPA, n-3) are precursors of eicosanoids and other lipid mediators which have critical roles in inflammation. The mediators formed from the different PUFA have different potencies. We hypothesised that metabolic changes associated with colonic mucosal inflammation would modify the bioavailability of the eicosanoid precursors AA and EPA.MethodsColonic mucosa biopsies were obtained from patients with ulcerative colitis and from matched controls. Inflammation was graded endoscopically and histologically. Esterified and non-esterified fatty acids were determined within the biopsies using gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry, respectively.ResultsBiopsy samples were collected from 69 UC patients (54 providing both inflamed and non-inflamed mucosa) and 69 controls. Inflamed mucosa had higher AA (p < 0.001) and lower EPA (p < 0.010) contents and a higher AA:EPA ratio (p < 0.001). Inflamed mucosa also had higher docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) and lower linoleic acid (LA) and α-linolenic acid (α-LNA) contents (all p < 0.001), compared to non-inflamed and controls. There were significant correlations between severity of inflammation and contents of AA, DPA and DHA (positive correlations) and of LA, α-LNA and EPA (negative correlations).ConclusionsHigher AA, AA:EPA ratio, DPA and DHA and lower LA, α-LNA and EPA are seen in inflamed mucosa in UC and correlate with severity of inflammation. This suggests an alteration in fatty acid metabolism in the inflamed gut mucosa, which may offer novel targets for intervention and should be considered if nutritional strategies are used.     

Type 2 diabetes mellitus and chronic hepatitis C: Which is worse? Results of a long-term retrospective cohort study

BackgroundThe long-term outcome in patients with chronic hepatitis C and type 2 diabetes mellitus treated with interferon and ribavirin is unclear. We compared incidence of liver-related events and mortality rates between hepatitis C virus-positive patients with or without diabetes mellitus, and the incidence of diabetes-related events between diabetic patients with and without hepatitis C.MethodsRetrospective study of 309 patients with chronic hepatitis C. Incidence of liver-related events, diabetes-related events and mortality rates were assessed over a mean follow-up of 11.02 ± 4.9 years.Results50 (16%) chronic hepatitis C patients had diabetes mellitus. Diabetics showed a higher number of diabetes- and liver-related events than non-diabetics (10% vs 1.5%, p = 0.006; 18% vs 5.7%, p = 0.007, respectively) with a mortality of 14% vs 1.5% (p = 0.0003). Baseline cirrhosis (p = 0.002) and non-sustained virological response (p = 0.01) were independent risk factors for liver events; diabetes mellitus (p = 0.01) and hypertension (p = 0.0017) were independent factors for diabetes-related events.ConclusionsIn patients with chronic hepatitis C, comorbidity with diabetes mellitus was associated with a higher mortality rate and incidence of liver/diabetes-related events. Independent risk factors for liver-related events were the non-response to antiviral therapy and cirrhosis at baseline.     

Significant differential effects of omega-3 fatty acids and fenofibrate in patients with hypertriglyceridemia

BackgroundOmega-3 fatty acids and fenofibrate are both used to treat patients with hypertriglyceridemia. However, a head-to-head comparison of the lipoprotein and metabolic effects of these two medicines has not been published.MethodsThis was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Fifty patients in each group were given placebo, omega-3 fatty acids 2 g (most commonly used dosage in Korean patients), or fenofibrate 160 mg, respectively daily for 2 months.ResultsOmega-3 fatty acids therapy decreased triglycerides by 21% and triglycerides/HDL cholesterol and improved flow-mediated dilation (P < 0.01), however, did not significantly change insulin, plasma adiponectin levels, and insulin sensitivity (determined by QUICKI) relative to baseline measurements. Fenofibrate therapy decreased total cholesterol, triglycerides by 29%, and triglycerides/HDL-cholesterol (all P < 0.01) and improved flow-mediated dilation when compared with baseline. When compared with placebo and omega-3 fatty acids, fenofibrate therapy decreased non-HDL cholesterol (P < 0.001) and triglycerides/HDL cholesterol (P = 0.016) while increasing HDL cholesterol (P < 0.001) and apolipoprotein AI (P = 0.001). Of note, when compared with omega-3 fatty acids, fenofibrate therapy decreased fasting insulin (P = 0.023) and increased plasma adiponectin (P = 0.002) and insulin sensitivity (P = 0.015).ConclusionsOmega-3 fatty acids and fenofibrate therapy promoted similar changes in triglycerides and endothelium-dependent dilation. However, fenofibrate therapy had substantially better effects on lipoprotein and metabolic profiles in patients with hypertriglyceridemia.     

Polyunsaturated fatty acids balance affects platelet NOX2 activity in patients with liver cirrhosis

BackgroundNADPH-oxidase-2 up-regulation has been suggested in liver damage perpetuation via an oxidative stress-mediated mechanism. n-6/n-3 polyunsaturated fatty acids ratio derangement has been reported in liver disease.AimTo explore polyunsaturated fatty acids balance and its interplay with platelet oxidative stress in liver cirrhosis.MethodsA cross-sectional study in 51 cirrhotic patients and sex- and age-matched controls was performed. Serum polyunsaturated fatty acids and oxidative stress markers (urinary isoprostanes and serum soluble NADPH-oxidase-2-derived peptide) were measured. The effect on platelet oxidative stress of n-6/n-3 polyunsaturated fatty acids ratio in vitro and in vivo (1-week supplementation with 3 g/daily n-3-polyunsaturated fatty acids) was tested.ResultsCompared to controls, cirrhotic patients had significantly higher n-6/n-3 polyunsaturated fatty acids ratio. n-6/n-3 polyunsaturated fatty acids ratio correlated significantly with disease severity and oxidative stress markers. In vitro experiments showed that in Child–Pugh C patients’ platelets incubation with low n-6/n-3 polyunsaturated fatty acids ratio resulted in dose-dependent decrease of radical oxigen species (−39%), isoprostanes (−25%) and NADPH-oxidase-2 regulation (−51%). n-3 polyunsaturated fatty acids supplemented patients showed significant oxidative stress indexes reduction.ConclusionsIn cirrhosis, n-6/n-3 polyunsaturated fatty acids imbalance up-regulates platelet NADPH-oxidase-2 with ensuing oxidative stress. Further study to evaluate if n-3 supplementation may reduce disease progression is warranted.     

Prevalence of gastroparesis-related symptoms in an unselected cohort of patients with Type 1 diabetes

BackgroundThe prevalence of diabetic gastroparesis is not well defined because of discrepancy between objective measurements, i.e. gastric emptying time, and symptoms experienced by patients. Furthermore most studies have been performed on small selected cohorts.ObjectiveTo determine the prevalence of clinical symptoms of diabetic gastroparesis in a large unselected cohort of out-patients with Type 1 diabetes.Methods1028 patients with Type 1 diabetes attending a specialized diabetes clinic were mailed a validated questionnaire; “patient assessment of upper gastrointestinal disorders-symptom severity index”, in which a subset of questions measures symptoms of gastroparesis (GCSI; Gastroparesis Cardinal Symptom Index). Response rate was 74.4% (n = 765). All patients were classified according to presence or absence of late diabetic complications and clinical and paraclinical data were obtained.ResultsA GCSI Total Score ≥ 1.90 signified definite symptoms of gastroparesis (n = 102) and patient charts were investigated for concomitant illness and/or medication influencing gastric emptying. In 30 patients an alternative etiology was revealed, leaving 72 (9.8%) patients with symptoms related to diabetic gastroparesis. Only 8 patients were previously diagnosed. HbA_1c levels were significantly higher in patients with diabetic gastroparesis (8.4 ± 1.3 vs. 8.2 ± 1.2 respectively, p = 0.02). Furthermore, patients with diabetic gastroparesis had more retinopathy (p = 0.006) and peripheral polyneuropathy (16.7% vs. 6.7%, p < 0.001) and there was a trend for diabetic nephropathy being more common (p = 0.08).ConclusionsSymptoms of diabetic gastroparesis affect approximately 10% of patients with Type 1 diabetes in a specialized diabetes clinic and are associated with poor glycemic control and other late diabetic complications.     

The G-250A polymorphism in the hepatic lipase gene promoter is associated with changes in hepatic lipase activity and LDL cholesterol: The KANWU Study

Background and aimsHepatic lipase (HL) catalyzes the hydrolysis of triglycerides and phospholipids from lipoproteins, and promotes the hepatic uptake of lipoproteins. A common G-250A polymorphism in the promoter of the hepatic lipase gene (LIPC) has been described. The aim was to study the effects of the G-250A polymorphism on HL activity, serum lipid profile and insulin sensitivity.Methods and resultsAltogether 151 healthy subjects (age 49 ± 8 years, BMI 26.5 ± 3.0 kg/m²) were randomly assigned for 3 months to an isoenergetic diet containing either a high proportion of saturated fatty acids (SFA diet) or monounsaturated fatty acids (MUFA diet). Within groups there was a second random assignment to supplements with fish oil (3.6 g n-3 FA/day) or placebo. At baseline, the A-250A genotype was associated with high serum LDL cholesterol concentration (P = 0.030 among three genotypes). On the MUFA diet carriers of the A-250A genotype presented a greater decrease in LDL cholesterol concentration than subjects with other genotypes (P = 0.007 among three genotypes). The rare -250A allele was related to low HL activity (P < 0.001 among three genotypes). The diet did not affect the levels of HL activity among the genotypes.ConclusionThe A-250A genotype of the LIPC gene was associated with high LDL cholesterol concentration, but the MUFA-enriched diet reduced serum LDL cholesterol concentration especially in subjects with the A-250A genotype.     

The prevalence of renal artery stenosis among patients with diabetes mellitus

BackgroundPatients with diabetes mellitus (DM) have a high prevalence of atherosclerotic vascular lesions. It is therefore reasonable to assume that also the rate of renal artery stenosis (RAS) is higher. The presence of a RAS can have implications for the treatment of patients with diabetes mellitus and hypertension and renal impairment. Therefore it is important to be informed about the chance that a RAS is present among such patients.MethodsWe prospectively studied the prevalence of atherosclerotic renal artery stenosis (RAS) among patients with diabetes mellitus. Patients were included if they were diagnosed with DM and hypertension with or without impairment of renal function. If causes of renal disease other than DM or hypertension were more probable on the basis of biochemical data, then such patients were excluded. A magnetic resonance angiography (MRA) of the renal arteries was made in 54 included successive patients.ResultsPatient characteristics: mean age 59 ± 8.5 years (range 35 to 80). Eight patients had DM 1 and 46 DM 2. Mean BMI was 31.4 ± 5.6 kg/m². A RAS was present in 18 of the 54 (33%) patients, 3 patients had bilateral stenoses. Factors related to the presence of RAS were diastolic blood pressure, glomerular filtration rate and dyslipidaemia.ConclusionIn this group of diabetic patients with hypertension and or renal impairment the prevalence of RAS was 33%.     

Effects on post-prandial glucose and AGE precursors from two initial insulin strategies in patients with Type 2 diabetes uncontrolled by oral agents

ObjectiveProgressive β-cell dysfunction in Type 2 diabetes results in the need for insulin therapy in many patients. Yet the best regimen to prescribe to patients transitioning from oral anti-hyperglycemic drugs (OADs) is not clear. We sought to compare the effects of two standard initial insulin strategies (basal insulin alone versus premixed insulin) on post-prandial glucose metabolism and precursors of advanced glycation end-products in patients with type 2 diabetes suboptimally controlled on OADs.Research Design and MethodsThis was a 6-month, open-label, single-center study using a cross-over design. 14 subjects were randomized to one of two protocols: once daily insulin glargine or twice-daily 75%/25% neutral protamine lispro/lispro mix. At 12 weeks, the subjects were crossed-over to the opposite protocol. During each period, insulin doses were titrated to target fasting blood glucose of 90–110mg/dL. At baseline and after the two 12-week treatment periods, subjects were studied in the Clinical Research Center; they consumed three liquid mixed isocaloric meals at 4-h intervals, and glucose, free fatty acids (FFA), lipids, and α-dicarbonyls (3-deoxyglucosone [3-DG] and methylglyoxal [MG]) were measured before and after each meal. Patient data were analyzed in the context of their assigned insulin strategy groups.ResultBoth insulin regimens led to a significant improvement in glycemic profiles, including fasting glucose and HbA1c, compared to baseline. However, mean post-prandial glucose was lower with lispro mix than with glargine (153 ± 36 vs. 199 ± 49 mg/dL, respectively; P = 0.001). Likewise, there was a reduction in both fasting (48 ± 13 vs. 57 ± 19, P = 0.047) and post-prandial (53 ± 19 vs. 63 ± 23; P = 0.007) 3DG levels with lispro mix as compared to glargine. No differences were noted in MG concentrations.ConclusionIn type 2 diabetes patients failing OAD therapy, an initial insulin regimen of twice daily premixed insulin results in significantly improved post-prandial glucose levels as well as a reduction in a precursor of AGEs. The effect of these two initial insulin regimens on long-term diabetic complications requires further study.