0000000000122572
AUTHOR
Laurence Duvillard
Increased erythrocytes n-3 and n-6 polyunsaturated fatty acids is significantly associated with a lower prevalence of steatosis in patients with type 2 diabetes
Summary Background & aims Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, metabolic syndrome and type 2 diabetes. Although dietary fat contributes substantially to the accumulation of liver fat, the role of individual fatty acids in this accumulation is unclear. Objective In this study, we set out to determine whether liver fat content (LFC), was associated with red blood cell fatty acid (RBC-FA) composition in people with type 2 diabetes. Design, settings, and participants One hundred and sixty-two type 2 diabetic patients were included in this study. LFC was measured using 1H-MR Spectroscopy. RBC-FA composition was measured by gas chromatography. Results One…
Liraglutide reduces plasma PCSK9 in patients with type 2 diabetes not treated with statins
Dyslipidaemia in type 2 diabetes mellitus (T2DM), which increases cardiovascular risk, includes abnormal metabolism of low-density lipoproteins (LDL). Our group has recently shown that liraglutide increases LDL catabolism in patients with T2DM and that it reduces the expression of PCSK9 (a major inhibitor of LDL-receptor expression) in vitro and in mice. This prompted us to study the effect of liraglutide on plasma PCSK9 level in patients with T2DM.We studied prospectively 82 patients with T2DM (51 without statins, 31 with statins). Plasma PCSK9 and plasma lipids were measured before and six months after the initiation of a treatment with liraglutide at a dose of 1.2 mg/day.Plasma PCSK9 was…
Additional file 1: Table S1. of Apolipoprotein B is regulated by gonadotropins and constitutes a predictive biomarker of IVF outcomes
Patients' characteristics. All values are reported by the mean ± SD (Standard Deviation) or the number of subjects (percentage of the total). BMI, Body Mass Index; IVF, In Vitro Fertilization; ICSI, Intracytoplasmic Sperm Injection. (DOCX 12 kb)
No Improvement of High-Density Lipoprotein (HDL) Vasorelaxant Effect Despite Increase in HDL Cholesterol Concentration in Type 2 Diabetic Patients Treated With Glitazones
Abstract Context: High-density lipoproteins (HDLs) from type 2 diabetic patients are unable to counteract the inhibitory effect of oxidized low-density lipoproteins (ox-LDLs) on vasorelaxation. We hypothesized that glitazones, which improve glycemic control and dyslipidemia, could correct this abnormality. Objectives and Design: We compared the ability of HDL from controls (n = 12) and from type 2 diabetic patients before and after 6 months of treatment with either rosiglitazone (n = 11) or pioglitazone (n = 8) to counteract the inhibitory effect of ox-LDL on vasodilatation of rabbit aorta rings. Results: Rosiglitazone induced a decrease in hemoglobin A1c (7.7% ± 1.1% vs 9.8% ± 1.0%, P = .0…
PNPLA3 polymorphism influences liver fibrosis in unselected patients with type 2 diabetes
Context: Recently, it has been shown that an allele in the adiponutrin (PNPLA3) gene was strongly associated with increased liver fat content (LFC) and liver fibrosis independent of visceral adiposity and insulin resistance. Objective: In this study, we set out to determine whether the PNPLA3 rs738409 polymorphism was associated with liver fibrosis in unselected patients with type 2 diabetes. Design, setting and participants: Two hundred and thirty-four patients with type 2 diabetes were included in this study. Main outcome measures: LFC was evaluated using 1H-MR spectroscopy; fibrosis was measured using the non-invasive FibroTest®. Results: Advanced liver fibrosis (stage F2 or above) was o…
Vitamin D supplementation, bone turnover, and inflammation in HIV-infected patients
IF 1.307 (2017); International audience; ObjectiveTo assess whether vitamin D supplementation could be associated with a modification of inflammatory markers and bone turnover in HIV-1-infected patients.Patients and methodsPatients who participated in an initial survey in 2010 and who were followed in the same department were included in a new study in 2012. Between 2010 and 2012, vitamin D supplementation was offered to patients presenting with hypovitaminosis D as per appropriate guidelines. Clinical examinations were performed, and fasting blood samples were taken for inflammation and bone marker evaluations.ResultsOf the 263 patients who participated in the 2010 study, 198 were included…
Impact of asymmetric dimethylarginine on mortality after acute myocardial infarction.
Objective— Asymmetrical dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthases. From a prospective cohort of patients with acute myocardial infarction (MI), we aimed to analyze the predictive value of circulating ADMA concentrations on prognosis. Methods and Results— Blood samples from 249 consecutive patients hospitalized for acute MI <24 hours were taken on admission. Serum levels of ADMA and its stereoisomer, symmetrical dimethylarginine (SDMA), were determined using high-performance liquid chromatography. The independent predictors of ADMA were glomerular filtration rate, female sex, and SDMA ( R 2 =0. 25). Baseline ADMA levels were higher in p…
No change in apolipoprotein AI metabolism when subcutaneous insulin infusion is replaced by intraperitoneal insulin infusion in type 1 diabetic patients.
In type 1 diabetic patients, the replacement of subcutaneous insulin infusion by intraperitoneal insulin infusion restores the normal physiological gradient between the portal vein and the peripheral circulation, which is likely to modify HDL metabolism. This stable isotope kinetic study was designed to compare HDL apolipoprotein (apo) AI metabolism in seven type 1 diabetic patients first treated by continuous subcutaneous insulin infusion by an external pump and then 3 months after the beginning of intraperitoneal insulin infusion by an implantable pump. Glycaemic control was comparable under subcutaneous and intraperitoneal insulin infusion (HbA1c=7.34+/-0.94% versus 7.24+/-1.00%, NS). HD…
Liraglutide reduces postprandial hyperlipidaemia by increasing apoB48 catabolism and by reducing apoB48 production
IF 6.080; International audience
Type 1 diabetes is not associated with an increased prevalence of hepatic steatosis
Aim Non-alcoholic fatty liver disease (NAFLD) is commonly associated with Type 2 diabetes. Recently, it has been suggested that NAFLD is also frequently associated with Type 1 diabetes and diabetic complications. In this study, we set out to determine whether Type 1 diabetes was associated with liver fat content measured using magnetic resonance imaging. Methods One hundred and twenty-eight patients with Type 1 diabetes, 264 patients with Type 2 diabetes and 67 participants without diabetes were included in this study. Hepatic steatosis was defined as a liver fat content > 5.5%. Results People with Type 1 diabetes and controls were similar for age and BMI. Liver fat content was significantl…
Additional file 2: Table S2. of Apolipoprotein B is regulated by gonadotropins and constitutes a predictive biomarker of IVF outcomes
Description of patients' characteristics according to APOB concentrations divided into quartiles. Q1, quartile 1; Q2, quartile 2; Q3, quartile 3; Q4, quartile 4; SD, Standard Deviation; CI, Confidence Intervals, BMI, Body Mass Index; IVF, In Vitro Fertilization; ICSI, Intracytoplasmic Sperm Injection. (DOCX 15Â kb)
Circulating Apelin is increased in patients with type 1 or type 2 diabetes and is associated with better glycaemic control
SummaryContext Apelin is an adipokine expressed in several tissues and it appears to be involved in energy metabolism. Objective The aim of this study was to determine serum apelin levels in a large cohort of patients with type 1 and type 2 diabetes and control subjects and to correlate the results with glycaemic control. Design and Participants One hundred and thirty patients with type 1 diabetes, 98 patients with type 2 diabetes and 162 controls were enrolled in the study. Apelin levels were measured by enzyme-linked immunosorbent assay. Results Serum apelin levels were significantly higher in type 1 and type 2 diabetic patients than in controls (P < 0·0001). Serum apelin levels were high…
Plasma Renin Concentration is Associated With Hemodynamic Deficiency and Adverse Renal Outcome in Septic Shock.
International audience; Background: In septic shock, both systemic vasodilatation and glomerular arteriole dilatation are responsible for the drop in glomerular filtration observed in early acute kidney injury. Angiotensin II has been showed to act on both mechanisms. Our objective was to evaluate the impact of renin angiotensin system activation, on hemodynamic deficiency and renal outcome in patient with septic shock and to assess whether urinary sodium could be a reliable test for high plasma renin concentration screening.Methods: This was a prospective and observational study. Inclusion criteria were 1) early septic shock (first episode) 2) dose of norepinephrine ≥ 0.25 μg/kg/min 3) bef…
O29 Diminution du contenu en sphingosine-1-phosphate dans les lipoprotéines de haute densité (HDL) au cours du diabète de type 1
Introduction La fonctionnalite des HDL des patients diabetiques de type 1 (DT1) est alteree. Ces anomalies sont en partie attribuables a des modifications glycoxydatives mais pourraient egalement s'expliquer par des variations de la composition en phospholipides et sphingolipides a la surface des HDL, molecules qui jouent un role important dans les differentes fonctions des HDL. Patients et methodes Nous avons recrute 43 patients DT1 (âge : 44,3±16,1 ; 17 hommes, 19 femmes) et 36 sujets controles normolipidemiques (âge : 40,3±14,6 ; 18 hommes, 25 femmes). Nous avons etabli la composition en phospholipides et sphingolipides des HDL par chromatographie liquide couplee a la spectrometrie de ma…
Liver Fat Content in People with Pituitary Diseases: Influence of Serum IGF1 Levels
AbstractNon-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, metabolic syndrome, and type 2 diabetes. NAFLD is also seen in patients with endocrinopathies. However, the relationship between endocrine diseases and the development of NAFLD is not well known. In this study, we set out to determine whether liver fat content (LFC) was associated with IGF1 levels in people with pituitary diseases (PD). Eighty-nine patients with pituitary diseases and 74 healthy controls were included in this study. LFC was measured using MRI. Hepatic steatosis was defined as LFC>5.5%. Patients with PD were older, and had a higher BMI than healthy controls. LFC was significantly higher…
Inability of HDL from abdominally obese subjects to counteract the inhibitory effect of oxidized LDL on vasorelaxation.
Abdominal obesity is associated with a decreased plasma concentration of HDL cholesterol and with qualitative modifications of HDL, such as triglyceride enrichment. Our aim was to determine, in isolated aorta rings, whether HDL from obese subjects can counteract the inhibitory effect of oxidized low density lipoprotein (OxLDL) on endothelium-dependent vasodilation as efficiently as HDL from normolipidemic, lean subjects. Plasma triglycerides were 74% higher (P < 0.005) in obese subjects compared with controls, and apolipoprotein A-I (apoA-I) and HDL cholesterol concentrations were 12% and 17% lower (P < 0.05), respectively. HDL from control subjects significantly reduced the inhibitory effe…
Liraglutide Increases the Catabolism of Apolipoprotein B100–Containing Lipoproteins in Patients With Type 2 Diabetes and Reduces Proprotein Convertase Subtilisin/Kexin Type 9 Expression
OBJECTIVE Dyslipidemia observed in type 2 diabetes (T2D) is atherogenic. Important features of diabetic dyslipidemia are increased levels of triglyceride-rich lipoproteins and small dense LDL particles, which all have apolipoprotein B100 (apoB100) as a major apolipoprotein. This prompted us to study the effect of the GLP-1 agonist liraglutide on the metabolism of apoB100-containing lipoproteins. RESEARCH DESIGN AND METHODS We performed an in vivo kinetic study with stable isotopes (L-[1-13C]leucine) in 10 patients with T2D before and after 6 months of treatment with liraglutide (1.2 mg/day). We also evaluated in mice the effect of liraglutide on the expression of genes involved in apoB100-…
Anti-hypertensive effects of Rosuvastatin are associated with decreased inflammation and oxidative stress markers in hypertensive rats
International audience; Among their pleiotropic effects, statins exert antioxidant and anti-inflammatory properties. The aim of this study was to evaluate in normotensive (WKY) and in spontaneously hypertensive rats (SHR) the effect of rosuvastatin (ROSU) treatment on (1) plasma inflammation markers and endogenous NO synthase inhibitor (ADMA) levels, (2) reactive oxygen species (ROS) generated by circulating leukocytes and (3) vascular oxidative stress and tissue inflammation markers. Plasma cytokines were higher in SHR than in WKY, except for IL-4, which was lower in SHR than in WKY. SHR monocytes exhibited higher production of ROS than did WKY monocytes. In the experimental conditions, RO…
Chronic Hyperinsulinemia Does Not Increase the Production Rate of High-Density Lipoprotein Apolipoprotein AI
Objective— In vitro studies showed that insulin stimulates the production of apolipoprotein AI (apoAI). Thus, we hypothesized that chronic hyperinsulinemia could contribute to the increase in the production of high-density lipoprotein apoAI that is observed in metabolic syndrome. Approach and Results— We performed an in vivo kinetic study with stable isotope in 7 patients with insulinoma who showed hyperinsulinemia but no insulin resistance, 8 patients with insulin resistance, and 16 controls. Insulinemia was 3.1× ( P <0.01) higher in patients with insulinoma or insulin resistance than in controls in the fasting state and, respectively, 3.5× and 2.6× ( P <0.05) higher in the fed stat…
Impact pronostique de la concentration de 3-hydroxymyristate sur la survie des patients atteints de cirrhose alcoolique ou virale
Etat de la question Le role de l’endotoxemie liee a la translocation bacterienne sur l’aggravation de la cirrhose fait l’objet de nombreuses etudes, mais son impact sur la mortalite au cours de la cirrhose est mal connu. Le but de ce travail etait d’etudier l’impact de la concentration sanguine de 3-hydroxymyristate (3-HM) total (composant specifique des lipopolysaccharides, endotoxine), sur le risque de deces et de complications des malades cirrhotiques. Materiel et methodes Au total, 593 patients atteints de cirrhose alcoolique ou virale, sans carcinome hepatocellulaire ont ete inclus entre 2008 et 2012 dans six centres hospitalo-universitaires francais. Le dosage de 3-HM total, libre et …
Interférences des traitements par biotine avec les immunodosages : il est temps de trouver une solution à long terme !
La Presse Medicale - In Press.Proof corrected by the author Available online since vendredi 22 decembre 2017
Glycation des HDL et conséquences chez le patient diabétique
Resume Les HDL ont un role majeur dans l’homeostasie vasculaire. Leur action protectrice passe notamment par leur recepteur specifique SR-BI (pour scavenger receptor de classe B type 1 ). La glycation des HDL, phenomene majeur observe au cours d’un diabete, a de nombreuses consequences nefastes vasculaires. La glycation des HDL entraine une augmentation de leur catabolisme, un defaut du transport inverse du cholesterol, une perte de leurs proprietes anti-inflammatoires et anti-oxydantes, notamment sur les LDL oxydees, lipoproteines atherogenes presentes en abondance dans les maladies chroniques. Cliniquement, cela se traduit par une dysfonction endotheliale, phenomene cardiovasculaire delet…
Asymmetric dimethylarginine (ADMA) and hyperhomocysteinemia in patients with acute myocardial infarction
We sought to investigate the association between increased levels of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, and total plasma homocysteinemia (tHcy) in patients with acute myocardial infarction (AMI).In 138 patients hospitalized for AMI24 h on admission, serum levels of ADMA, its symmetric stereoisomer (SDMA) and tHcy were measured.ADMA was positively associated with SDMA (p0.001) and tHcy (p=0.03) but not with estimated glomerular filtration rates (eGFR, p=0.96), while tHcy strongly correlated with eGFR (p=0.002) and SDMA (p0.001). By multiple linear regression, SDMA but not ADMA was independently associated with tHcy (p=0.005).Our findings sugges…
Apolipoprotein B is regulated by gonadotropins and constitutes a predictive biomarker of IVF outcomes
Background Follicular fluid (FF) is an important micro-environment influencing oocyte growth, its development competence, and embryo viability. The FF content analysis allows to identify new relevant biomarkers, which could be predictive of in vitro fertilization (IVF) outcomes. Inside ovarian follicle, the amount of FF components from granulosa cells (GC) secretion, could be regulated by gonadotropins, which play a major role in follicle development. Methods This prospective study included 61 female undergoing IVF or Intra-cytoplasmic sperm injection (ICSI) procedure. Apolipoprotein B (APOB) concentrations in follicular fluid and APOB gene and protein expression in granulosa cells from rep…
Short-term atorvastatin treatment does not modify neointimal morphology but reduces MMP-2 expression in normocholesterolemic rabbit stented arteries.
The aim of our study was to explore some potential pleiotropic effects of atorvastatin, after stenting in the iliac arteries of normocholesterolemic rabbits. On day 0, 27 rabbits underwent stent implantation and were randomized into either the control group (standard chow, CTRL, n = 15) or the atorvastatin group (10 mg/kg/d per os, Ator, n = 12). On day 30, the stented arteries were harvested for histomorphometry and neointimal analysis [macrophages, matrix metalloproteinases (MMP-2), tissue inhibitor of metalloproteinase-2, vascular smooth muscle cells, and collagen]. Atorvastatin did not induce significant histomorphometric and inflammatory modifications but reduced neointimal expression …
Distinct patterns of heparin affinity chromatography VLDL1 and VLDL2 subfractions in the different dyslipidaemias
Very low density lipoprotein (VLDL) 1 and 2 were fractionated by heparin affinity chromatography into a bound and an unbound fraction and the different subfractions were quantified in 17 normolipidaemic (NL), 13 hypercholesterolaemic (HC), 10 hypertriglyceridaemic (HTG) and 11 combined hyperlipidaemic subjects (CHL). Unbound VLDL1 and VLDL2 were, respectively, 1.9- and 2.2-fold richer in triglycerides than bound VLDL1 and VLDL2. In HTG and CHL the concentration of all the VLDL subfractions was increased and plasma triglyceride level was correlated to unbound VLDL1 and to bound VLDL1 (respectively, r=0.86 (p<0.001) and r=0.77 (p<0.01) in HTG and r=0.73 (p<0.001) and r=0.62 (p<0.05) in CHL). …
Deleterious effect of glycation on the ability of HDL to counteract the inhibitory effect of oxidized LDL on endothelium-dependent vasorelaxation
Background Contrary to high-density lipoprotein (HDL) from normolipidaemic and normoglycaemic subjects, HDL from diabetic patients loses its ability to reverse the inhibition of vasorelaxation induced by oxidized low-density lipoprotein (LDL). The aim of this study was to analyze the role of glycation, a major abnormality observed in diabetes, on the impairment of the vasorelaxant effect of HDL. Methods HDL from healthy subjects was glycated in vitro by incubation in glucose 200 mmol/L for 3 days. Vasoreactivity was evaluated by the relaxation response to acetylcholine of rabbit aorta rings pre-contracted with noradrenaline, before and after 2 h incubation with or without different lipoprot…
Liraglutide Reduces Postprandial Hyperlipidemia by Increasing ApoB48 (Apolipoprotein B48) Catabolism and by Reducing ApoB48 Production in Patients With Type 2 Diabetes Mellitus
Objective— Treatment with liraglutide, a GLP-1 (glucagon-like peptide-1) agonist, has been shown to reduce postprandial lipidemia, an important feature of diabetic dyslipidemia. However, the underlying mechanisms for this effect remain unknown. This prompted us to study the effect of liraglutide on the metabolism of ApoB48 (apolipoprotein B48). Approach and Results— We performed an in vivo kinetic study with stable isotopes (D 8 -valine) in the fed state in 10 patients with type 2 diabetes mellitus before treatment and 6 months after the initiation of treatment with liraglutide (1.2 mg/d). We also evaluated, in mice, the effect of a 1-week liraglutide treatment on postload triglycerides an…
CO-74: Altérations majeures du sphingophospholipidome des lipoprotéines de haute densité (HDL) de patients avec syndrome métabolique et glycémie normale
Rationnel Les phospholipides et sphingolipides jouent un role primordial dans la fonctionnalite et le role anti-atherogene des HDL. Ces proprietes sont alterees chez les patients porteurs d'un syndrome metabolique avant meme l'apparition d'une hyperglycemie. Nous avons donc recherche si les HDL de ces patients presentaient des anomalies de leur sphingophospholipidome. Patients et Methodes Par chromatographie liquide couplee a la spectrometrie de masse en tandem, nous avons quantifie 80 especes moleculaires des principales classes de phospholipides et sphingolipides des HDL2 et HDL3, chez 26 patients avec un syndrome metabolique et une glycemie a jeun nor-male (14 hommes, 12 femmes, âge moye…
Severe hypovitaminosis D correlates with increased inflammatory markers in HIV infected patients
Abstract Background Even though it has been suggested that antiretroviral therapy has an impact on severe hypovitaminosis D (SHD) in HIV infected patients, it could be speculated that the different levels of residual inflammation on HAART (Highly Active Anti Retroviral Therapy) could contribute to SHD and aggravate bone catabolism in these patients. Methods A cross-sectional study was carried out in an unselected cohort of 263 HIV infected outpatients consulting during Spring 2010. Clinical examinations were performed and medical history, food habits, sun exposure and addictions were collected. Fasting blood samples were taken for immunological, virological, inflammation, endocrine and bone…
Increased body fat mass reduces the association between fructosamine and glycated hemoglobin in obese type 2 diabetes patients
Abstract Obesity is increasing in patients with type 2 diabetes. A possible reduced association between fructosamine and glycated hemoglobin (HbA1c) in obese individuals has been previously discussed, but this has never been specifically evaluated in type 2 diabetes, and the potential influence of body fat mass and fat distribution has never been studied. We studied 112 type 2 diabetes patients with assessment of fat mass, liver fat and fat distribution. Patients with body mass index (BMI) above the median (34.9 kg/m2), versus BMI below the median, had a correlation coefficient between fructosamine and HbA1c significantly reduced (r = 0.358 vs r = 0.765). In the whole population, fructosami…
Time course of asymmetric dimethylarginine (ADMA) and oxidative stress in fructose-hypertensive rats: A model related to metabolic syndrome
Asymmetric dimethylarginine (ADMA) is an endogenous modulator of endothelial function and oxidative stress, and increased levels of this molecule have been reported in some metabolic disorders and cardiovascular diseases. The aim of this work was to analyze the time course of dimethylarginine compounds and oxidative stress levels and the relationship between these and cardiovascular function in fructose-hypertensive rats.90 male Sprague-Dawley rats were randomized into 2 groups, fed for 3 months with standard (C) chow supplemented or not with fructose (F, 60%). After sacrifice at different weeks (W), the aorta and plasma were harvested to assess the vascular and biochemical parameters. Our …
Additional file 3: Figure S1. of Apolipoprotein B is regulated by gonadotropins and constitutes a predictive biomarker of IVF outcomes
17 β-estradiol quantification (ng/l) into culture medium by immuno-chemiluminescence. Androstenedione (And) was added to the culture medium to provide specific substrate to granulosa cells, for oestrogen synthesis. (TIF 69 kb)
Additional file 3: Figure S1. of Apolipoprotein B is regulated by gonadotropins and constitutes a predictive biomarker of IVF outcomes
17 β-estradiol quantification (ng/l) into culture medium by immuno-chemiluminescence. Androstenedione (And) was added to the culture medium to provide specific substrate to granulosa cells, for oestrogen synthesis. (TIF 69 kb)
Additional file 4: Figure S2. of Apolipoprotein B is regulated by gonadotropins and constitutes a predictive biomarker of IVF outcomes
The constant GAPDH gene expression in GC pools (n = 10) under our experiment conditions. All Ct-values were reported for the different GC pools from FF samples. (JPG 137 kb)
Additional file 4: Figure S2. of Apolipoprotein B is regulated by gonadotropins and constitutes a predictive biomarker of IVF outcomes
The constant GAPDH gene expression in GC pools (n = 10) under our experiment conditions. All Ct-values were reported for the different GC pools from FF samples. (JPG 137 kb)