Laurence Duvillard

Centre Hospitalier Universitaire de Dijon, Dijon, Bourgogne, France

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Publications (95)311.05 Total impact

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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; · 6.50 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; · 7.74 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; · 4.63 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. © 2013 S. Karger AG, Basel.
    Ophthalmic Research 11/2013; 51(1):42-45. · 1.56 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; · 2.24 Impact Factor
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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; · 6.34 Impact Factor
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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 07/2013; · 2.97 Impact Factor
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    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 markers evaluations. RESULTS: Ninety-five (36%) patients had SHD. In univariate analysis, a significant and positive association was found between SHD and IL6 (p = 0.001), hsCRP (p = 0.04), increased serum C-Telopeptides X (CTX) (p = 0.005) and Parathyroid Hormon (PTH) (p < 0.0001) levels. In multivariate analysis, SHD deficiency correlated significantly with increased IL-6, high serum CTX levels, lower mean daily exposure to the sun, current or past smoking, hepatitis C, and functional status (falls), but not with the time spent on the current HAART (by specific drug or overall). CONCLUSIONS: SHD is frequent and correlates with inflammation in HIV infected patients. Since SHD is also associated with falls and increased bone catabolism, it may be of interest to take into account not only the type of antiretroviral therapy but also the residual inflammation on HAART in order to assess functional and bone risks. This finding also suggests that vitamin D supplementation may be beneficial in these HIV-infected patients.
    BMC Infectious Diseases 01/2013; 13(1):7. · 3.03 Impact Factor
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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 01/2013; 7(5):431–436.
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    ABSTRACT: OBJECTIVES: Our objective was to develop a reference method to measure total cholesterol in human serum, in order to assign values and assess the accuracy of field methods in French clinical laboratories. DESIGN AND METHODS: A reference method based on gas chromatography coupled with mass spectrometry and isotope dilution (GC-IDMS) was developed and validated. It was then used to assign reference values to five frozen serum samples from voluntary Proficiency Testing schemes gathering 170 French clinical laboratories. Three peer groups were defined and bias against the reference method target value was calculated. RESULTS: Accuracy of the reference method was assessed against NIST SRM 1951b. Bias of the reference method was less than 0.5% and imprecision was less than 1.0%. Our study indicated that field methods tended to overestimate total cholesterol concentration, mean bias being +5.02% ± 1.02%. The most popular methods (phenolic chromogen with spectrophotometric detection, 80% of participants) exhibited the highest bias (peer group mean bias : +5.51 ± 1.24%). Neither these methods nor those using a non-phenolic chromogen with reflectometric detection (10% of participants, peer group mean bias : +4.20 ± 1.44 %) met NCEP recommendations according to which bias should be less than 3%. Only methods using a non phenolic chromogen with a spectrophotometric detection met these recommendations (10% of participants, peer group mean bias : +1.39 ± 2.75 %) CONCLUSIONS: As all three peer groups provided positively biased results, the consensus mean usually used to assess the trueness of routine methods is biased as well, which results in a erroneous estimation of method bias. Therefore, this study highlights the value added by reference method target values to assess trueness of field methods and monitor performance of clinical laboratories.
    Clinical biochemistry 12/2012; · 2.02 Impact Factor
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    ABSTRACT: OBJECTIVE: Retinol-binding protein 4 (rbp4) is an adipokine secreted by adipocytes and liver, whose levels are elevated in type 2 diabetes mellitus (T2DM). Plasma levels of rbp4 and triglycerides are strongly correlated in T2DM. However, we do not know whether this association is direct or indirect via liver fat content, and the link between rbp4 and triglyceride metabolism remains unknown. METHODS AND RESULTS: Liver fat measurement by proton spectroscopy was performed in 221 patients with T2DM, and an in vivo kinetic study with stable isotopes was carried out in 14 patients with T2DM. In multivariate analysis, triglycerides were associated positively with rbp4 (β=0.273, P<0.0001), apolipoprotein (apo) B (β=0.258, P<0.0001), and liver fat (β=0.191, P=0.002) and negatively with high-density lipoprotein cholesterol (β=-0.442, P<0.0001). rbp4 was correlated positively with apoB100 very-low-density lipoprotein (VLDL) pool (r=0.62, P=0.017) and negatively with VLDL-apoB100 total fractional catabolic rate (r=-0.66, P=0.001). In multivariate analysis, rbp4 (P=0.015), plasma triglycerides (P=0.024), and sex (P=0.026) were independently associated with VLDL-apoB100 total fractional catabolic rate. CONCLUSIONS: In T2DM, plasma rbp4 level is associated with plasma triglycerides, independently of liver fat content. There is a strong independent negative correlation between plasma rbp4 and VLDL-apoB100 total fractional catabolic rate. These data suggest that rbp4 may be involved in the pathophysiology of hypertriglyceridemia in T2DM by reducing VLDL catabolism.
    Arteriosclerosis Thrombosis and Vascular Biology 10/2012; · 6.34 Impact Factor
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    ABSTRACT: We investigated how liver fat content (LFC) influences cholesterol metabolism by quantifying liver fat using proton magnetic resonance spectroscopy and by measuring the serum concentrations of lathosterol, a marker of cholesterol synthesis, and sitosterol and campesterol, two markers of cholesterol absorption. We also evaluated whether this relationship could be modified by statin therapy. The study was conducted in 263 patients with type 2 diabetes, 137 of whom (52.0%) received statin therapy. RESULTS: One hundred and sixty-five patients (62.7%) had steatosis (LFC>5.5%). We performed specific analyses in patients without statin therapy and in patients treated with statin therapy. In both groups, the lathosterol to cholesterol ratio correlated positively with LFC, and in multivariate analysis, the lathosterol to cholesterol ratio was associated with LFC independently of age, gender and BMI. Sitosterol and campesterol concentrations were not associated with LFC. CONCLUSIONS: Our study suggests that in patients with type 2 diabetes, LFC is associated with an increase in cholesterol synthesis that is independent of obesity or diabetes mellitus. Statin therapy does not modify this relationship.
    Atherosclerosis 08/2012; 224(2):465-8. · 3.71 Impact Factor
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    ABSTRACT: 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. 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. One hundred and sixty-two type 2 diabetic patients were included in this study. LFC was measured using (1)H-MR Spectroscopy. RBC-FA composition was measured by gas chromatography. One hundred and nine (67.2%) patients had steatosis. Patients with steatosis had a higher BMI (p = 0.0005), and higher plasma triglyceride levels (p = 0.009) than did patients without steatosis. We report a significant association between palmitic acid (16:0), palmitoleic acid (16:1n-7) concentrations and ratio of monounsaturated to saturated fatty acid (palmitoleic acid to palmitic acid) and higher liver fat content. Total polyunsaturated fatty acid (PUFA), homo-gamma-linolenic acid (20:3n-6), docosahexaenoic acid (22:6n-3), and arachidonic acid (20:4 n-6) were associated with lower LFC. Our data showed that an increased erythrocytes long-chain n-3 and n-6 fatty acids was associated with a lower prevalence of steatosis in patients with type 2 diabetes. These results suggest that n-3 and n-6 fatty acids supplementation could be a promising treatment for NAFLD in patients with type 2 diabetes.
    Clinical nutrition (Edinburgh, Scotland) 12/2011; 31(4):520-5. · 3.27 Impact Factor
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    ABSTRACT: The SteatoTest, fatty liver index (FLI) and hepatic steatosis index (HSI) are clinico-biological scores of steatosis validated in general or selected populations. Serum adiponectin (s-adiponectin) and retinol binding protein 4 (s-RBP4) are adipokines that could predict liver steatosis. We investigated whether the Steatotest, FLI, HSI, s-adiponectin and s-RBP4 could be valid predictors of liver steatosis in type-2 diabetic (T2D) patients. We enrolled 220 consecutive T2D patients. Reference standard was 3.0 T (1)H-MR spectroscopy (corrected for T1 and T2 decays). Intraclass correlation coefficients (ICCs), Kappa statistic measures of agreement, receiver operating characteristic (ROC) curves were assessed. Median liver fat content was 91 mg triglyceride/g liver tissue (range: 0-392). ICCs among the Steatotest, FLI, HSI, s-adiponectin, s-RBP4 and spectroscopy were low: 0.384, 0.281, 0.087, -0.297 and 0.048. Agreement between scores and spectroscopy was poor (Kappa range: 0.042-0.281). The areas under the ROC curves were low: 0.674, 0.647, 0.637, 0.616 and 0.540. S-adiponectin and s-RBP4 levels were strongly related to the presence of diabetic nephropathy (P = 0.0037 and P = 0.004; Mann-Whitney). The SteatoTest, FLI, HSI, s-adiponectin, s-RBP4 are not valid predictors of steatosis in T2D patients. Clino-biological markers cannot replace (1)H-MR spectroscopy for the assessment of liver fat in this population. (1) H-MR spectrosopy can reliably estimate the weight fraction of liver steatosis. Type-2 diabetes provides an interesting model for assessing liver steatosis. Clinico-biological markers seem to be invalid predictors for steatosis in type-2 diabetes.
    European Radiology 11/2011; 22(4):855-63. · 3.55 Impact Factor
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    ABSTRACT: Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a post-transcriptional inhibitor of LDL-receptor. In non-diabetic men, plasma PCSK9 levels were found to be inversely correlated with low-density lipoprotein (LDL) apolipoprotein B100 (apoB) fractional catabolic rate (FCR). Here, we aimed to determine the effect of type 2 diabetes on the association between plasma PCSK9 and FCR of LDL. A kinetic study of LDL-apoB100, using stable isotopes, was performed in 38 individuals (20 men, 18 women) including 23 non-diabetic normolipidemic subjects and 15 patients with type 2 diabetes. In the non-diabetic group, plasma PCSK9 was positively correlated with LDL-C (r=0.64, p=0.001), apoB (r=0.67, p<0.001), and inversely correlated with LDL-apoB FCR (r=-0.61, p=0.002). In contrast, in type 2 diabetic patients, plasma PCSK9 was not associated with LDL-C, apoB and LDL-apoB FCR. However, the lack of association between PCSK9 and LDL-apoB FCR seemed to be limited to the patients with "uncontrolled" diabetes (HbA1c>7%) since a borderline significant negative correlation between PCSK9 and LDL FCR (r=-0.70, p=0.08) was retrieved in patients with HbA1c≤7%. In multivariate analysis, LDL-apoB FCR was independently associated with PCSK9 (p=0.001) and fasting glycaemia (log) (p=0.030) in the non-diabetic population and with PCSK9 (p=0.040) and HbA1c (p=0.029) in diabetic patients. Our data indicate that both PCSK9 and glycaemia are independent factors influencing LDL catabolism. Plasma PCSK9 influences significantly the catabolism of LDL-apoB100 in individuals without diabetes, but not in patients with uncontrolled type 2 diabetes. Thus, the influence of diabetes on LDL-apoB FCR catabolism may overwhelm the influence of PCSK9.
    Atherosclerosis 07/2011; 219(1):342-8. · 3.71 Impact Factor
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    ABSTRACT: 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. 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. Two hundred and thirty-four patients with type 2 diabetes were included in this study. LFC was evaluated using (1) H-MR spectroscopy; fibrosis was measured using the non-invasive FibroTest(®). Advanced liver fibrosis (stage F2 or above) was observed in 10.2% of the patients while 149 (63.6%) patients had steatosis. The prevalence of steatosis and fibrosis was higher in minor G allele carriers than that in C allele homozygote carriers (70.3 vs 57.1%; P=0.04 and 14.7 vs 7.5%; P=0.07 respectively). In multivariate analysis, the predictive variables for advanced liver fibrosis were age (≥60) (P=0.005), sex (female) (P=0.004) and rs 738409 PNPLA3 polymorphism (P=0.01); body mass index (BMI) and LFC were not associated with liver fibrosis. This study confirms that in patients with type 2 diabetes who were not selected for liver abnormalities, liver fibrosis was related to the rs738409 polymorphism independent of BMI or LFC.
    Liver international: official journal of the International Association for the Study of the Liver 06/2011; 31(9):1332-6. · 3.87 Impact Factor
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    ABSTRACT: We performed a study in 102 people with type 2 diabetes aiming to determine "easy-to-use" predictive factors for glycemic response to glitazones. We found that low baseline HDL-cholesterol (<40 mg/L [1.04 mmol/L] in males, <50 mg/L [1.30 mmol/L] in females) was a strong independent predictor of glycemic response to glitazones (OR=2.67 [2.02-3.52], p=0.0004).
    Diabetes research and clinical practice 04/2011; 93(1):e44-8. · 2.74 Impact Factor
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    ABSTRACT: It is currently suggested that chronic hyperinsulinemia is a causal factor for the increased production rate of very-low-density lipoproteins (VLDL) associated with metabolic syndrome. However, the involvement of hyperinsulinemia independently of the other abnormalities also observed in metabolic syndrome has never been proven in humans. We used patients with insulinoma showing hyperinsulinemia but no insulin resistance as a model and conducted an apolipoprotein B (apoB) kinetic study in seven patients with insulinoma, seven insulin-resistant (IR) obese patients, and 12 controls. Insulinemia was higher in patients with insulinoma or IR than in controls both in the fasting state [2.4-fold (P = 0.039) and 3.1-fold (P = 0.003), respectively] and in the fed state [3.5-fold (P = 0.006) and 2.6-fold (P = 0.05), respectively]. Patients with insulinoma were not IR (steady state plasma glucose = 80 ± 46 mg/dl, a value lower than in IR subjects (231 ± 75, P = 0.0013). In the fed state, triglyceridemia and VLDL apoB pool size were higher in IR subjects compared with controls and patients with insulinoma [208 ± 56 vs. 89 ± 30 mg/dl (P < 0.0001) and 96 ± 42 mg/dl (P < 0.0001), respectively, for triglyceridemia and 3.56 ± 0.60 vs. 1.85 ± 0.88 mg/kg (P = 0.004) and 2.32 ± 1.79 (P = 0.052) mg/kg for VLDL apoB pool size]. The production rate of VLDL apoB in subjects with insulinoma was not significantly different from that in controls (14.56 ± 7.43 vs. 16.40 ± 7.70 mg/kg · d) but was higher in IR subjects compared with these two groups [25.66 ± 12.84 mg/kg · d (P = 0.046 and 0.035, respectively)]. Chronic endogenous hyperinsulinemia is not directly responsible for any increase in the production rate of VLDL apoB in humans.
    The Journal of clinical endocrinology and metabolism 03/2011; 96(7):2163-70. · 6.50 Impact Factor
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    ABSTRACT: 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 work showed that the plasma levels of ADMA in the fructose-fed rats increased after 2 weeks of the diet (1.6 ± 0.3 μM vs. 1.2 ± 0.3 μM, p < 0.05) with no changes in plasma levels of either SDMA or L-arginine and after an increase in glycemia. Levels of vascular oxidative stress, estimated in aortic segments using an oxidative fluorescence technique, were higher in the F group (W2: 1.14 ± 0.2% vs. 0.33 ± 0.02%, p < 0.01). An increase in expression levels of nitrotyrosine (3-fold) and iNOS (2-fold) were noted in the fructose-fed rats. After 1 month, this was associated with a significant increase in NAD(P)H oxidase activity. Concerning vascular function, a 15% decrease in maximal endothelium-dependent relaxation was found in the aorta of the F group. Our work showed that the presence of exogenous L-MMA, an inhibitor of NO synthase, was associated with a significant reduction in endothelium-dependent relaxation in isolated aorta rings of the C group; this effect was not observed in the vessels of fructose-fed rats. Our findings suggest that the elevated levels of ADMA observed could in part be secondary to the early development of oxidative stress associated with the development of hypertension.
    Atherosclerosis 02/2011; 214(2):310-5. · 3.71 Impact Factor
  • Diabetes & Metabolism - DIABETES METAB. 01/2011; 37(1).

Publication Stats

762 Citations
311.05 Total Impact Points

Institutions

  • 2003–2012
    • Centre Hospitalier Universitaire de Dijon
      • Endocrinology, Diabetes and Metabolic Diseases Service
      Dijon, Bourgogne, France
    • 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
  • 2000–2011
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2000–2008
    • University of Burgundy
      Dijon, Bourgogne, France
  • 2002–2004
    • Hôpital Universitaire Necker
      Lutetia Parisorum, Île-de-France, France