Laurence Duvillard

Unité Inserm U1077, Caen, Lower Normandy, France

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Publications (118)439.84 Total impact

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    ABSTRACT: Objectives: The objective of this study was to assess clinical and biological changes during intermittent ART (I-ART) started early, with significant time spent on versus off ART, which has never before been studied in ART-naive patients with high nadir and current CD4 cell count. Patients and methods: ART-naive HIV-1-infected patients with baseline CD4 ≥500/mm(3) and nadir CD4 ≥400/mm(3) received 2 years of I-ART (6 month periods on once-daily boosted-PI-based ART, alternating with 6 month periods without ART) in a 2 year, Phase II, non-comparative multicentre trial. The trial is registered with, number NCT 00820118. Results: The CD4 cell count remained ≥500/mm(3) at 2 years in all 44 patients included in the study. The mean 2 year count was higher than the mean count at baseline in 24 patients overall (55%; 95% CI 40%-69%) and in 20 (65%; 95% CI 48%-81%) of the 31 patients who fully adhered to the trial strategy. All but three of these latter patients had HIV-1 RNA concentrations below 50 copies/mL after each 6 month 'on' period. Only one strategy-related genotypic mutation (M184I) was detected. The HIV-1 DNA median load fluctuated, but it did not differ between month 0 and month 24 (2.8 versus 2.6 log10 copies/10(6) leucocytes, P = 0.29). Biomarkers of inflammation and endothelial activation remained stable between month 0 and month 24. Naive CD4, CD8+CCR5+ and CD8+CD38+ T cell numbers tended to decline. One patient developed Burkitt's lymphoma and 12 patients reported sexually transmitted infections. Conclusions: In patients with high nadir and current CD4 cell counts, 2 year I-ART maintained the CD4 cell count above 500/mm(3), with no increase in the viral reservoir. Immune activation seems related to HIV replication, while inflammation seems to evolve independently and require specific attention.
    Journal of Antimicrobial Chemotherapy 11/2015; DOI:10.1093/jac/dkv369 · 5.31 Impact Factor
  • Damien Denimal · Stéphanie Lemaire-Ewing · Laurence Duvillard ·

    Clinical biochemistry 09/2015; DOI:10.1016/j.clinbiochem.2015.08.027 · 2.28 Impact Factor
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    ABSTRACT: Phospholipids and sphingolipids are major components of HDL. They play a critical role in HDL functionality and protective effects against atherosclerosis. As HDL are dysfunctional in type 1 diabetic patients, we ascertained whether they presented abnormalities in their phospholipid and sphingolipid profile, despite normal HDL cholesterol concentration. Using liquid chromatography-tandem mass spectrometry, we quantified the main species of phosphatidylcholines, sphingomyelins, lysophophatidylcholines, phosphatidylethanolamines, phosphatidylinositols, ceramides, plasmalogens and sphingosines 1-phosphate in the HDL2 and HDL3 from 54 type 1 diabetic patients and 50 controls. Serum HDL cholesterol was similar in the 2 groups of subjects. When data were expressed relative to the total amount of phospholipids and sphingolipids, sphingosines-1-phosphate (S1P) were 11.7% (NS) and 14.4% (p = 0.0062) lower in HDL2 and HDL3, respectively, from type 1 diabetic patients than from controls. Ceramides were 23% (p = 0.005) and 24% (borderline significance) lower in HDL2 and HDL3, respectively. The concentration of apolipoprotein M, the carrier of S1P, was similar in patients and controls. In type 1 diabetic patients compared to controls, the concentration of d18:1-S1P, the main S1P species, was decreased in total plasma (-17.0%, p < 0.0001), HDL fraction (-21.9%, p < 0.0001) and non-HDL fraction (-13.7%, p = 0.012). The concentration of ceramides was decreased in total plasma (-24.4%, p < 0.0001), HDL fraction (-27.9%, p = 0.0006) and non-HDL fraction (-22.0%, p = 0.0087). Despite normal HDL cholesterol level, the phospholipid + sphingolipid profile is impaired in HDL from type 1 diabetic patients. These abnormalities, especially the decrease in S1P, could contribute to the impaired HDL functionality observed in these patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 08/2015; 241(2). DOI:10.1016/j.atherosclerosis.2015.06.040 · 3.99 Impact Factor
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    ABSTRACT: It has recently been shown that an allele in the glucokinase regulatory protein (GCKR) gene was associated with increased liver fat content in obese children. In this study, we set out to determine whether GCKR rs1260326 polymorphism was associated with liver fat content in patients with type 2 diabetes. Three hundred and eight patients with type 2 diabetes were included in this study. Liver fat content was evaluated using 1H-MR spectroscopy. In our population, carriers of the rs1260326 minor T allele had a higher liver fat content than did carriers of the C allele homozygote (12.4 ± 9.6 vs. 10.3 ± 9.1 %, p = 0.03). The number of patients with steatosis was significantly higher in minor T allele carriers than in C allele homozygote carriers (70.7 vs. 55.4 %; p = 0.008). In multivariate analysis, the predictive variables for steatosis were BMI [odds ratio (OR) 1.08; 95 % confidence interval (CI) 1.03-1.13; p = 0.002], statin therapy (yes) [OR 0.54; 95 % CI 0.31-0.94; p = 0.03], metformin therapy (yes) [OR 2.67; 95 % CI 1.50-4.75; p < 0.001], and rs1260326 GCKR polymorphism (TT+CT) [OR 1.99; 95 % CI 1.14-3.47; p = 0.01]. This study shows that in patients with type 2 diabetes who were not selected for liver abnormalities, liver fat content was related to GCKR rs1260326 polymorphism independent of BMI, triglyceride levels, and age.
    Acta Diabetologica 05/2015; DOI:10.1007/s00592-015-0766-4 · 2.40 Impact Factor
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    ABSTRACT: 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. 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%. People with Type 1 diabetes and controls were similar for age and BMI. Liver fat content was significantly higher in patients with Type 2 diabetes than in patients with Type 1 diabetes and controls. In the control group, nine people (13.4%) had steatosis compared with six (4.7%) patients with Type 1 diabetes (P = 0.04). Among patients with Type 2 diabetes group, 166 (62.8%) had steatosis. In multivariate analysis that included patients with Type 1 diabetes and participants without diabetes, steatosis was associated only with BMI, whereas age, sex, statin therapy and Type 1 diabetes were not. In patients with Type 1 diabetes, there was no correlation between liver fat content and estimated glomerular filtration rate or carotid intima media thickness. Our data showed that Type 1 diabetes was not associated with an increased prevalence of steatosis. Moreover, our study provided no specific arguments concerning a link between liver fat content and diabetic complications in patients with Type 1 diabetes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Diabetic Medicine 05/2015; DOI:10.1111/dme.12805 · 3.12 Impact Factor

  • Diabetes & Metabolism 03/2015; 41. DOI:10.1016/S1262-3636(15)30004-5 · 3.27 Impact Factor
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    ABSTRACT: Chronic inflammation is a key feature of colorectal cancer (CRC), meaning that inflammatory biomarkers may be useful for its diagnosis. In particular, high neutrophil gelatinase-associated lipocalin (NGAL) expression has been reported in CRC. Thus, we investigated whether serum NGAL and NGAL/MMP-9 could be potential biomarkers for the early detection of CRC. Concurrently, we studied other inflammatory biomarkers such as soluble tumor necrosis factor receptor 1 and 2 (sTNFR-1, sTNFR-2), and C reactive protein (CRP). The AGARIC multicenter case-control study was performed in eastern France and included patients admitted for elective surgery either for a priori non-metastatic incident CRC (n = 224) or for benign causes (n = 252). Pre-operative serum levels of NGAL, NGAL/MMP-9, sTNFR-1, sTNFR-2 and CRP were measured. Median values of serum NGAL, NGAL/MMP-9, sTNFR-1, sTNFR-2 and CRP were significantly higher in CRC patients than in controls. Receiver Operating Characteristic analysis provided relatively poor values of area under the curve, ranging from 0.65 to 0.58. Except for NGAL/MMP-9, all biological parameters were strongly correlated in CRC cases and, less strongly in controls. Multivariate odds ratio (OR) of CRC comparing the extreme tertiles of serum NGAL was 2.76 (95% confidence interval (CI): 1.59-4.78; p < 0.001),. Lower but significant multivariate associations were observed for sTNFR-1, and sTNFR-2: OR = 2.44 (95% CI : 1.34-4.45, p = 0.015) and 1.93 (95% : CI 1.12-3.31), respectively. No independent association was found between case-control status and NGAL/MMP-9. Among CRC cases, maximal tumor size was an independent determinant of serum NGAL (p = 0.028) but this association was reduced after adjustment for CRP (p = 0.11). Despite a significant increase in serum NGAL and other inflammatory markers among CRC patients, our findings suggest that they may not be suitable biomarkers for the diagnosis and especially early detection of CRC.
    BMC Cancer 12/2014; 14(1):912. DOI:10.1186/1471-2407-14-912 · 3.36 Impact Factor

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    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 = .003) and an increase in HDL cholesterol (1.14 ± 0.32 vs 0.98 ± 0.24 mmol/L, P = .033). Pioglitazone induced a decrease in hemoglobin A1c (8.3% ± 2.5% vs 9.5% ± 3.2%, P = .068) and serum triglycerides (1.58 ± 0.89 vs 2.03 ± 0.70 mmol/L, P = .069) and an increase in HDL cholesterol (1.39 ± 0.22 vs 1.14 ± 0.22 mmol/L, P = .018). The triglyceride content of HDL was unchanged by rosiglitazone and was decreased by 25% (P = .068) by pioglitazone. HDL from controls counteracted the inhibitory effect of ox-LDL on vasodilatation (maximal relaxation [Emax] = 74.4% ± 3.5% vs 51.9% ± 3.3%, P = .0029), whereas HDL from type 2 diabetic patients did not (Emax = 51.7% ± 5.8% vs 52.3% ± 4.6% [P = .66] and 52.7% ± 5.5% vs 51.9% ± 4.5% [P = .78] for the rosiglitazone and pioglitazone group, respectively). Rosiglitazone or pioglitazone did not improve Emax (58.6% ± 5.9% vs 52.3% ± 4.6% [P = .15] and 49.3% ± 6.5% vs 51.9% ± 4.5% [P = .48], respectively). Conclusion: Glitazones increased the concentration of HDL cholesterol without restoring the ability of HDL particles to protect the endothelium from oxidative stress-induced dysfunction, meaning that HDL remained dysfunctional with impaired antiatherogenic properties.
    Journal of Clinical Endocrinology &amp Metabolism 08/2014; 99(10):jc20142078. DOI:10.1210/jc.2014-2078 · 6.21 Impact Factor
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    ABSTRACT: Context: Low plasma HDL cholesterol is a major abnormality in abdominal obesity. This relates due to accelerated HDL catabolism but the underlying mechanism requires further elucidation. The relationships between HDL catabolism and other variables that may be modified in abdominal obesity, such as VLDL subspecies (VLDL1, VLDL2) kinetics, liver fat or visceral adiposity, remain to be investigated. Objectives: Our aim was to study the associations between HDL apoA-I fractional catabolic rate (FCR) and the kinetics of VLDL subspecies and estimates of liver, visceral and subcutaneous fat. Design: We carried out a multicentre in vivo kinetic study using stable isotopes (deuterated leucine and glycerol) in 62 individuals with abdominal obesity. Results: In multivariate analysis, among the morphological and biological parameters that may predict ApoA-I FCR, liver fat (β=0.400, p=0.003) and VLDL1-apoB (β=0.307, p=0.020) were independently associated with apoA-I FCR. In multivariate analysis, among the kinetic parameters, VLDL1-TG indirect FCR (β=-0.357, p=0.001), VLDL1-TG PR (β= 0.213p=0.048) and apoA-II FCR (β=0.667, p<0.0001) were independently associated with apoA-I FCR. After adjustment for VLDL1-TG PR, liver fat was no more correlated with apoA-I FCR. No association between apoA-I FCR and visceral fat was observed. Conclusions: We show that VLDL1 is an important independent determinant of apoA-I FCR and more precisely that apoA-I FCR is independently associated with both catabolism and production of VLDL1-TG. In addition, we show an association between liver fat and apoA-I FCR that is mostly mediated by VLDL1-TG production. These data indicate that, in abdominal obesity, dysfunctional VLDL1 metabolism is an important modulator of HDL apoA-I catabolism.
    Journal of Clinical Endocrinology &amp Metabolism 07/2014; 99(11):jc20142365. DOI:10.1210/jc.2014-2365 · 6.21 Impact Factor
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    ABSTRACT: Several current diseases are associated with an increase in the oxidation of HDL, which is likely to impair their functionality. Our aim was to identify whether oxidation could change the protective effect of HDL against the deleterious effect on vasoreactivity induced by oxidative stress. HDL from healthy subjects were oxidized in vitro by Cu(2+), and the ability of oxidized HDL to counteract the inhibitory effect of oxidized LDL on acetylcholine-induced vasodilation was tested on isolated rabbit aorta rings. Oxidation of HDL was evidenced by the increase in the 7-oxysterols/cholesterol ratio (3.20 ± 1.12 vs 0.02 ± 0.01 % in native HDL, p < 0.05). Oxidized LDL inhibited endothelium-dependent vasodilation (E max = 50.2 ± 5.0 vs 92.5 ± 1.7 % for incubation in Kreb's buffer, p < 0.05) and native HDL counteracted this inhibition (E max = 72.4 ± 4.8 vs 50.2 ± 5.0 % p < 0.05). At the opposite, oxidized HDL had no effect on oxidized LDL-induced inhibition on endothelium-dependent vasorelaxation (E max = 53.7 ± 4.8 vs 50.2 ± 5.0 %, NS). HDL oxidation is associated with a decreased ability of HDL to remove 7-oxysterols from oxidized LDL. In conclusion, these results show that oxidation of HDL induces the loss of their protective effect against endothelial dysfunction, which could promote atherosclerosis in diseases associated with increased oxidative stress.
    Heart and Vessels 07/2014; 30(6). DOI:10.1007/s00380-014-0543-2 · 2.07 Impact Factor
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    ABSTRACT: Context: Lipopolysaccharides (LPS) are inflammatory components of the outer membrane of gram-negative bacteria, and in plasma, are mostly associated with lipoproteins. This association is thought to promote their catabolism while reducing their pro-inflammatory effects. Objectives: Our aim was to determine the impact of lipoprotein kinetics on plasma LPS distribution and how it may affect patients with type 2 diabetes [T2DM]. Design: We performed a kinetic study in 30 individuals (16 T2DM patients, 14 controls) and analyzed the impact of changes in lipoprotein kinetics on LPS distribution among lipoproteins. Results: Plasma LPS levels in T2DM patients were not different from those in controls, but LPS distribution in the two groups was different. Patients with T2DM had higher LPS-VLDL (31±7 vs. 22±11%, p=0.002), LPS-HDL (29±9 vs. 19±10%, p=0.015), free (non-lipoprotein bound) LPS (10±4 vs. 7±4%, p=0.043) and lower LPS-LDL (30±13 vs. 52±16%, p=0.001). In multivariable analysis, VLDL-LPS was associated with HDL-LPS (p<0.0001); LDL-LPS was associated with VLDL-LPS (p=0.004) and VLDL apoB100 catabolism (p=0.002); HDL-LPS was associated with free LPS (p<0.0001) and VLDL-LPS (p=0.033); free LPS was associated with HDL-LPS (p<0.0001). In a patient featuring dramatic decrease in VLDL catabolism due to apoA-V mutation, LDL-LPS was severely decreased (0.044 EU/ml vs. 0.788 EU/ml in controls). The difference between T2DM patients and controls for LDL-LPS fraction was no longer significant after controlling for VLDL apoB100 total FCR. Conclusions: Our data suggest that in humans, free LPS transfers first to HDL and then to VLDL whereas the LPS-bound LDL fraction is mainly derived from VLDL catabolism; the latter may hence represent a LPS catabolic pathway. T2DM patients show lower LDL-LPS secondary to reduced VLDL catabolism, which may represent an impaired catabolic pathway.
    The Journal of Clinical Endocrinology and Metabolism 04/2014; 99(7):jc20133463. DOI:10.1210/jc.2013-3463 · 6.21 Impact Factor

  • Diabetes & Metabolism 03/2014; 40:A74. DOI:10.1016/S1262-3636(14)72485-1 · 3.27 Impact Factor
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    ABSTRACT: OBJECTIVE Apolipoprotein (apo)C1 is a potent physiological inhibitor of cholesteryl ester transfer protein (CETP). ApoC1 operates through its ability to modify the electrostatic charge at the lipoprotein surface. We aimed to determine whether the inhibitory ability of apoC1 is still effective in vivo in patients with diabetes and whether in vitro glycation of apoC1 influences its electrostatic charge and its CETP inhibitory effectRESEARCH DESIGN AND METHODS ApoC1 concentrations and CETP activity were measured in 70 type 1 diabetic (T1D) patients, 113 patients with type 2 diabetes, and 83 control subjects. The consequences of in vitro glycation by methylglyoxal on the electrostatic properties of apoC1 and on its inhibitory effect on CETP activity were studied. An isoelectric analysis of apoC1 was performed in patients with T1D and in normolipidemic-normoglycemic subjects.RESULTSAn independent negative correlation was found between CETP activity and apoC1 in control subjects but not in patients with diabetes. HbA1c was independently associated with CETP activity in T1D patients. In vitro glycation of apoC1 modified its electrostatic charge and abrogated its ability to inhibit CETP activity in a concentration-dependent manner. The isoelectric point of apoC1 in T1D patients was significantly lower than that in control subjects.CONCLUSIONS The ability of apoC1 to inhibit CETP activity is impaired in patients with diabetes. Glycation of apoC1 leads to a change in its electrostatic properties that might account, at least in part, for a loss of constitutive CETP inhibition and an increase in plasma CETP activity in patients with diabetes.
    Diabetes care 02/2014; 37(4). DOI:10.2337/dc13-1467 · 8.42 Impact Factor
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    ABSTRACT: The association between liver cirrhosis (LC) and diabetes mellitus (DM) is well known. However, the impact of the severity or etiology of LC on the occurrence of DM is relatively unknown. We aimed to determine the prevalence and clinical correlates of DM in a large cohort of patients with cirrhosis. A total of 1,068 patients with LC were included in this cross sectional study (CIRCE study). The diagnosis of cirrhosis irrespective of its etiology was based on histological confirmation by liver biopsy or, in the absence of biopsy, on typical clinical, morphological and biological data. Data related to the cirrhosis etiology: alcohol, viral markers of hepatitis B, C, iron load parameters and autoimmune markers were collected for each patient. Venous blood samples were taken in the morning after 12-h overnight fasting. There were 383 patients with cirrhosis associated with hepatocellular carcinoma (HCC). DM was found in 412 (39.7 %) patients. Patients with DM were older and more likely to be overweight and male, with a family history of DM and a diagnosis of HCC. DM was not associated with a history of stroke or myocardial infarction. Cirrhosis secondary to hepatitis infection was less strongly associated with DM than with NASH or alcoholic cirrhosis. The severity of LC was not associated with DM. In multivariate analysis, the factors associated with DM were age, BMI, a family history of DM, and statin use. There was a significant interaction between HCC and cirrhosis etiology for the risk of DM. Cirrhosis secondary to hepatitis was associated with a lesser presence of DM only in patients with HCC (interaction p = 0.0015). LC was strongly associated with DM, with around 40 % of diabetic patients. In the group of patients with LC without HCC, diabetes was not associated with the etiology of cirrhosis.
    Acta Diabetologica 12/2013; 51(3). DOI:10.1007/s00592-013-0538-y · 2.40 Impact Factor
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    ABSTRACT: Aims: The link between diabetic retinopathy (DR) and adipokines is controversial. Some studies suggest that visceral fat and adipokines could be additional risk factors for DR. The aim of this study was to determine the relationship between abdominal fat or adipokine secretion and DR in patients with type 2 diabetes mellitus (DM). Methods: A total of 179 patients with type 2 DM were included. Each patient underwent measurement of plasma adiponectin and leptin and an evaluation of body fat distribution (visceral and subcutaneous) with MRI. The severity of DR was evaluated according to the classification of the American Academy of Ophthalmology. Patients were classified in 3 groups: absence of DR, mild and moderate DR, and advanced DR (severe, proliferative and laser-treated DR). Results: There were no significant differences between the 3 groups for adiponectin, leptin and visceral or subcutaneous fat accumulation. Patients with DR had a mean duration of diabetes, serum creatinine concentration and percentage of macroalbuminuria significantly higher than patients without DR (p < 0.001, p = 0.003 and p < 0.001, respectively). Serum adiponectin increased with the diabetic nephropathy stage (p = 0.007). Conclusions: Our study suggests that body fat distribution and adipokine secretion are not associated with DR in patients with type 2 DM.
    Ophthalmic Research 11/2013; 51(1):42-45. DOI:10.1159/000355323 · 1.42 Impact Factor
  • M C Brindisi · L Duvillard · S Monier · B Vergès · L Perségol ·
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    ABSTRACT: Contrary to HDL from normolipidaemic and normoglycaemic subjects, HDL from diabetic patients have lost their ability to reverse the inhibition of vasorelaxation induced by oxidized LDL. The aim of this study was to analyse the role of glycation, a major abnormality observed in diabetes, on the impairment of the vasorelaxant effect of HDL. HDL from healthy subjects, were glycated in vitro by incubation in glucose 200 mmolar for 3 days. Vasoreactivity was evaluated by the relaxation response to acetylcholine of rabbit aorta rings pre-contracted with noradrenaline, before and after two hours incubation with or without different lipoprotein fractions (Krebs'buffer; oxidized LDL; normal or glycated HDL alone and with oxidized LDL). The fructosamine/apolipoprotein AI ratio was significantly increased in glycated HDL compared to native HDL (53.63 ± 7.91 vs 18.51 ± 4.10 µmol/g; p < 0.05). Oxidized LDL inhibited endothelium-dependent vasodilation compared to Krebs'buffer (maximal relaxation (Emax) = 53.15 ± 6.50 vs 98.67 ± 2.07%, p < 0.001). Native HDL were able to counteract the oxidized LDL-induced inhibition of vasorelaxation (Emax = 76.93 ± 5.41 vs 53.15 ± 6.50%, p < 0.001). At the opposite, glycated HDL had no effect on oxidized LDL-induced inhibition on endothelium vasorelaxation compared to incubation with oxidized LDL alone (Emax = 52.98 ± 2.07 vs 53.15 ± 6.50%, NS). Glycation of HDL induces the loss of the ability of HDL to counteract the inhibitory effect of oxidized LDL on endothelium-dependent vasorelaxation, which is likely to contribute to the impairment of anti-atherogenic properties of HDL in diabetic patients. This article is protected by copyright. All rights reserved.
    Diabetes/Metabolism Research and Reviews 11/2013; 29(8). DOI:10.1002/dmrr.2434 · 3.55 Impact Factor
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    ABSTRACT: Infections are the leading cause of morbidity and mortality after colorectal surgery. Obesity is a well-known risk factor for wound infection, but it does not seem to increase the risk of other infectious complications. The aim of this study was to look for a relationship between the fatty tissue metabolism measured by adipocytokine levels and the risk of postoperative infection. Preoperative plasma levels of eight adipocytokines, cholesterol, triglycerides, insulin and C-reactive protein (CRP) were measured in consecutive patients undergoing elective colorectal surgery between June 2008 and June 2011. Information about epidemiological and clinical characteristics was obtained for each patient. All infections in the 30 days following surgery were recorded. Among the 174 patients included, 49 (28 %) presented with a postoperative infection: 41 surgical site infections and 8 other infections. Preoperative leptin, insulin and CRP were significantly higher in patients with postoperative infection (p = 0.025, p = 0.020 and p = 0.044, respectively), but only leptin was predictive of infection in multivariate analysis (odds ratio (OR) = 1.89, 95 % confidence interval (CI) 1.18-3.03, p = 0.008). The predictive value of leptin was slightly lower for surgical site infection (OR = 1.65, 95 % CI 1.06-2.55, p = 0.025). Leptin levels were independent of the other adipocytokine levels but not of the body mass index. Although markers of inflammation and insulin resistance are also related to the onset of surgical infection, leptin correlates more closely with the risk of infection than does any other factor. However, its effect could be partially mediated by the body mass index.
    International Journal of Colorectal Disease 10/2013; 29(1). DOI:10.1007/s00384-013-1782-x · 2.45 Impact Factor
  • M.-C. Brindisi · L. Duvillard · L. Perségol · B. Vergès ·
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    ABSTRACT: HDLs play a major role in vascular homeostasis. Their protective actions are mediated in part by their SR-BI specific receptor. HDLs glycation, huge phenomenon observed during diabetes mellitus lead to their increased catabolism, a decrease in the reverse transport of cholesterol, a loss of their antiinflammatory and antioxidant properties, particularly on oxidized LDL, abundant lipoparticules proatherogenic observed in chronic diseases. Endothelial dysfunction, a deleterious vascular phenomenon, observed in diabetes, is the clinical representation of these adverse effects of HDL glycation.
    Médecine des Maladies Métaboliques 10/2013; 7(5):431–436. DOI:10.1016/S1957-2557(13)70532-7
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    ABSTRACT: 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. 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 state. The high-density lipoprotein apoAI pool size was smaller in patients with insulin resistance than in controls (49.3±5.4 versus 59.6±7.7 mg·kg(-1); P<0.01), whereas both the high-density lipoprotein apoAI fractional catabolic rate and the high-density lipoprotein apoAI production rate were higher (0.30±0.07 versus 0.20±0.04 pool·d(-1); P<0.0001 and 14.6±1.5 versus 11.5±1.9 mg·kg(-1)·d(-1); P<0.01, respectively). In contrast, no significant difference was observed for these parameters between patients with insulinoma and controls. In patients with insulinoma, the apoAI pool size tended to be greater than in patients with insulin resistance (56.3±8.6 versus 49.3±5.4 mg·kg(-1); P=0.078), whereas both the apoAI fractional catabolic rate and the production rate were lower (0.20±0.06 versus 0.30±0.07 pool·d(-1); P<0.01 and 11.1±1.6 versus 14.6±1.5 mg·kg(-1)·d(-1); P<0.01, respectively). The apoAI fractional catabolic rate was the only variable associated with the apoAI production rate in multivariate analysis and explained 80% of its variance. Chronic endogenous hyperinsulinemia does not induce any increase in the apoAI production rate, which seems to be more dependent on the apoAI fractional catabolic rate.
    Arteriosclerosis Thrombosis and Vascular Biology 08/2013; 33(10). DOI:10.1161/ATVBAHA.113.301597 · 6.00 Impact Factor

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  • 2003-2015
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2007-2014
    • University of Burgundy
      Dijon, Bourgogne, France
  • 2004-2014
    • Centre Hospitalier Universitaire de Dijon
      • Department of Infectious Diseases
      Dijon, Bourgogne, France
  • 2003-2012
    • French Institute of Health and Medical Research
      • Center of Medicine, Sciences, Health, Mental Health and Health Policy CERMES 3
      Lutetia Parisorum, Île-de-France, France
  • 2000-2003
    • Hôpital Universitaire Necker
      Lutetia Parisorum, Île-de-France, France