Hugues Chevassus

Unité Inserm U1077, Caen, Lower Normandy, France

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Publications (25)80.07 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Clinical studies involve an increasing amount of data collection and management. However, there is no specific quality standard sufficiently practical, in free access, and open for data management and the underlying IT-infrastructure in academic units. ECRIN (European Clinical Research Infrastructures Network) published Standard requirements for certified data management units. We present a French version of these standards. A group of experts produced the standards, by consensus. The first version was revised after two pilot audits for data centre certification were performed. The revised version includes 21 lists of five to ten standards, in three groups: information technologies, data management (DM) and "general". These standards offer a clear description of DM and IT requirements for clinical studies. Initially created for ECRIN certification purposes, they offer a very useful reference for academic DM structures. © 2015 Société Française de Pharmacologie et de Thérapeutique.
    Thérapie 08/2015; DOI:10.2515/therapie/2015042 · 0.51 Impact Factor
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    ABSTRACT: OPA1 mutations are responsible for more than half of autosomal dominant optic atrophy (ADOA), a blinding disease affecting the retinal ganglion neurons. In most patients the clinical presentation is restricted to the optic nerve degeneration, albeit in 20% of them, additional neuro-sensorial symptoms might be associated to the loss of vision, as frequently encountered in mitochondrial diseases. This study describes clinical and neuroradiological features of OPA1 patients. Twenty two patients from 17 families with decreased visual acuity related to optic atrophy and carrying an OPA1 mutation were enrolled. Patients underwent neuro-ophthalmological examinations. Brain magnetic resonance imaging (T1, T2 and flair sequences) was performed on a 1.5-Tesla MR Unit. Twenty patients underwent 2-D proton spectroscopic imaging. Brain imaging disclosed abnormalities in 12 patients. Cerebellar atrophy mainly involving the vermis was observed in almost a quarter of the patients; other abnormalities included unspecific white matter hypersignal, hemispheric cortical atrophy, and lactate peak. Neurological examination disclosed one patient with a transient right hand motor deficit and ENT examination revealed hearing impairment in 6 patients. Patients with abnormal MRI were characterized by: (i) an older age (ii) more severe visual impairment with chronic visual acuity deterioration, and (iii) more frequent associated deafness. Our results demonstrate that brain imaging abnormalities are common in OPA1 patients, even in those with normal neurological examination. Lactate peak, cerebellar and cortical atrophies are consistent with the mitochondrial dysfunction related to OPA1 mutations and might result from widespread neuronal degeneration. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of the Neurological Sciences 01/2015; 349(1-2). DOI:10.1016/j.jns.2015.01.008 · 2.47 Impact Factor
  • E. Renard · J. Place · N. Ben Brahim · O. Diouri · H. Chevassus · A. Farret ·

    Diabetes & Metabolism 03/2014; 40:A116-A117. DOI:10.1016/S1262-3636(14)72662-X · 3.27 Impact Factor
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    ABSTRACT: Diffuse gliomas are incurable brain tumors divided in 3 WHO grades (II; III; IV) based on histological criteria. Grade II/III gliomas are clinically very heterogeneous and their prognosis somewhat unpredictable, preventing definition of appropriate treatment. On a cohort of 65 grade II/III glioma patients, a QPCR-based approach allowed selection of a biologically relevant gene list from which a gene signature significantly correlated to overall survival was extracted. This signature clustered the training cohort into two classes of low and high risk of progression and death, and similarly clustered two external independent test cohorts of 104 and 73 grade II/III patients. A 22-gene class predictor of the training clusters optimally distinguished poor from good prognosis patients (median survival of 13-20 months versus over 6 years) in the validation cohorts. This classification was stronger at predicting outcome than the WHO grade II/III classification (P≤2.8E-10 versus 0.018). When compared to other prognosis factors (histological subtype and genetic abnormalities) in a multivariate analysis, the 22-gene predictor remained significantly associated with overall survival. Early prediction of high risk patients (3% of WHO grade II), and low risk patients (29% of WHO grade III) in clinical routine will allow the development of more appropriate follow-up and treatments.
    PLoS ONE 06/2013; 8(6):e66574. DOI:10.1371/journal.pone.0066574 · 3.23 Impact Factor
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    ABSTRACT: Glioblastoma multiform (GBM) are devastating brain tumors containing a fraction of multipotent stem-like cells which are highly tumorigenic. These cells are resistant to treatments and are likely to be responsible for tumor recurrence. One approach to eliminate GBM stem-like cells would be to force their terminal differentiation. During development, neurons formation is controlled by neurogenic transcription factors such as Ngn1/2 and NeuroD1. We found that in comparison with oligodendrogenic genes, the expression of these neurogenic genes is low or absent in GBM tumors and derived cultures. We thus explored the effect of overexpressing these neurogenic genes in three CD133(+) Sox2(+) GBM stem-like cell cultures and the U87 glioma line. Introduction of Ngn2 in CD133(+) cultures induced massive cell death, proliferation arrest and a drastic reduction of neurosphere formation. Similar effects were observed with NeuroD1. Importantly, Ngn2 effects were accompanied by the downregulation of Olig2, Myc, Shh and upregulation of Dcx and NeuroD1 expression. The few surviving cells adopted a typical neuronal morphology and some of them generated action potentials. These cells appeared to be produced at the expense of GFAP(+) cells which were radically reduced after differentiation with Ngn2. In vivo, Ngn2-expressing cells were unable to form orthotopic tumors. In the U87 glioma line, Ngn2 could not induce neuronal differentiation although proliferation in vitro and tumoral growth in vivo were strongly reduced. By inducing cell death, cell cycle arrest or differentiation, this work supports further exploration of neurogenic proteins to oppose GBM stem-like and non-stem-like cell growth. © 2012 Wiley Periodicals, Inc.
    Glia 02/2013; 61(2). DOI:10.1002/glia.22429 · 6.03 Impact Factor
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    ABSTRACT: Purpose: Bupropion is largely used as an antidepressant and smoking cessation therapy. The aim of this work was to compare pharmacodynamic properties of bupropion and the amphetamine-like methylphenidate after sustained administration in humans. Methods: Twelve male volunteers completed this randomized, double-blind, placebo controlled, cross-over study. Bupropion and methylphenidate were administered separately for initial half-dose 6-day periods (150 and 10 mg respectively) followed by full-dose 8-day periods (300 and 20 mg respectively). Outcomes were subjective feelings, cognitive performances, autonomic and physiological parameters. Results: Data are expressed as mean(SEM). After repeated administration, bupropion, like methylphenidate, decreased asthenia-fatigue [44(3.2) and 42(3.7), respectively vs. 53(4.1) for placebo; p = 0.034], despite an impairment of sleep onset [-4.3(3.32) and -1.9(3.76), respectively vs. +7.5(3.69); p = 0.016]. Both drugs increased resting diastolic blood pressure [67.9(1.23) and 65.7(0.98), respectively vs. 62.5(1.42) mm Hg; p = 0.001], body temperature [36.5(0.12) and 36.5(0.14) vs. 36.3(0.10) °C; p = 0.037] and decreased body weight [-0.7(0.23) and -0.6(0.22), respectively vs. +0.2(0.27) kg; p = 0.038]. No significant change could be observed on cognitive functions, appetite and energy consumption. Conclusion: Although it may not share all the properties of stimulant drugs, the effect profile of bupropion presents a number of similarities with that of methylphenidate over a 2-week treatment period.
    European Journal of Clinical Pharmacology 10/2012; 69(4). DOI:10.1007/s00228-012-1418-z · 2.97 Impact Factor
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    ABSTRACT: Statin use may be limited by muscle side effects. Although incompletely understood to date, their pathophysiology may involve oxidative stress and impairments of mitochondrial function and of muscle Ca(2+) homeostasis. In order to simultaneously assess these mechanisms, 24 male healthy volunteers were randomized to receive either simvastatin for 80 mg daily or placebo for 8 weeks. Blood and urine samples and a stress test were performed at baseline and at follow-up, and mitochondrial respiration and Ca(2+) spark properties were evaluated on a muscle biopsy 4 days before the second stress test. Simvastatin-treated subjects were separated according to their median creatine kinase (CK) increase. Simvastatin treatment induced a significant elevation of aspartate amino transferase (3.38±5.68 vs -1.15±4.32 UI/L, P<0.001) and CK (-24.3±99.1±189.3 vs 48.3 UI/L, P=0.01) and a trend to an elevation of isoprostanes (193±408 vs 12±53 pmol/mmol creatinine, P=0.09) with no global change in mitochondrial respiration, lactate/pyruvate ratio or Ca(2+) sparks. However, among statin-treated subjects, those with the highest CK increase displayed a significantly lower Vmax rotenone succinate and an increase in Ca(2+) spark amplitude vs both subjects with the lowest CK increase and placebo-treated subjects. Moreover, Ca(2+) spark amplitude was positively correlated with treatment-induced CK increase in the whole group (r=0.71, P=0.0045). In conclusion, this study further supports that statin induced muscular toxicity may be related to alterations in mitochondrial respiration and muscle calcium homeostasis independently of underlying disease or concomitant medication.
    Toxicology and Applied Pharmacology 07/2012; 263(3):281-6. DOI:10.1016/j.taap.2012.06.020 · 3.71 Impact Factor
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    ABSTRACT: We aimed to examine whether long-term use of benzodiazepines is associated with an accelerated decline of cognitive performances by using a statistical model specifically adapted to multivariate longitudinal bounded quantitative outcomes. The data came from the "Three-city" study, a French population based study. All the subjects were 65 years old or older at inclusion and had been followed-up for 7 years. The use of benzodiazepines and cognitive functioning were assessed at each examination phase (baseline, 2, 4 and 7 years). Cognitive decline was analyzed using a nonlinear multivariate mixed model with a latent process. This model makes it possible to assess change over time of the latent cognitive process underlying several neuropsychological tests: Mini Mental Status Examination, Isaacs Set test, Benton Visual Retention Test, and Trail Making Test (A and B), and to describe and account for their metrological properties. Analyses were adjusted for age, center, gender, education, socio-professional status, depression, insomnia, high blood pressure, hypercholesterolemia, alcohol, tobacco consumption and physical activity. Nine hundred and sixty nine subjects who reported taking benzodiazepines for 2, 4 or 7 consecutive years were compared to 4226 subjects who were non-benzodiazepine users. Chronic use of benzodiazepine was significantly associated with a lower latent cognitive level (β=-1.79 SE=0.25 p=<0.001), but no association was found between chronic use and an acceleration of cognitive decline, neither on the latent cognitive process (β×time=0.010 SE=0.04 p=0.81), nor on specific neuropsychological tests. Our results suggest that chronic benzodiazepine use is associated with poorer cognitive performance but not with accelerated cognitive decline with age.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 06/2012; 23(3). DOI:10.1016/j.euroneuro.2012.05.004 · 4.37 Impact Factor
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    ABSTRACT: Introduction La glycémie postprandiale demeure difficile à contrôler dans le diabète de type 1 (DT1). Les bolus biphasiques (« combinés ») n’ont pas été évalués par rapport aux bolus immédiats standards, d’où la présente étude prospective, randomisée, contrôlée, en cross-over. Patients et méthodes Quarante patients DT1 sous pompe à insuline depuis au moins 6 mois (23 H/17 F, âge : 46,8+/− 10,9 ans, durée de diabète : 21,9+/− 10,3 ans, HbA1c : 7,4+/− 0,6 %; moyenne +/− SD) ont réalisé l’étude après un run-in d’un mois évaluant l’observance de l’autosurveillance glycémique (33 mesures par semaine, dont 12 postprandiales), avec des bolus immédiats. L’étude comprenait deux phases de 3 mois durant lesquelles les bolus-repas étaient soit immédiats, soit biphasiques : pour 70 % immédiats et pour 30 % étalés sur deux heures. La comparaison en modèle mixte pour données répétées, en cross-over, a été réalisée entre les deux derniers mois de chaque phase. Le critère de jugement principal était la dispersion glycémique, mesurée par l’écart-type (SD) des glycémies. Résultats L’analyse en intention de traiter montre, lors de l’utilisation des bolus immédiats, une moindre dispersion glycémique (mg/dl) : 69+/−2 vs. 72+/− 2 (moyenne +/− SEM; p = 0,001), ainsi qu’une glycémie (mg/dl) plus faible : 146+/−3 vs. 152+/−3 (p < 0,0001), sans effet période. Alors que les glycémies et les SD préprandiaux sont similaires (137+/−3 vs. 139+/−3 et 64+/−2 vs. 65+/−2), les glycémies postprandiales sont significativement plus faibles avec les bolus immédiats : 159+/−3 vs. 169+/−3 (p < 0,0001). L’HbA1c était similaire à l’inclusion et en fin de chaque période. Discussion Les bolus immédiats permettent une moindre dispersion glycémique et un meilleur contrôle glycémique postprandial que les bolus combinés systématiques dans le DT1 sous pompe à insuline. Le choix du bolus n’a cependant pas d’effet sur l’HbA1c. L’orientation vers un bolus spécifique pourrait être justifiée ponctuellement selon la prise alimentaire et la vidange gastrique.
    Diabetes & Metabolism 03/2012; 38:A6. DOI:10.1016/S1262-3636(12)71001-7 · 3.27 Impact Factor
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    ABSTRACT: Introduction Les statines sont largement prescrites en prévention cardiovasculaire, notamment chez les diabétiques, mais 1 à 7% des sujets peuvent présenter une myopathie sous statines, de physiopathologie incomplètement élucidée. L’objectif de notre étude était d’évaluer simultanément plusieurs mécanismes potentiellement impliqués dans cette myopathie. Matériels et méthodes 24 hommes sains (27.5 ± 6,1 ans, poids stable, IMC 22.8 ± 1.5), ont été inclus dans cette étude randomisée, en groupes parallèles (simvastatine 80 mg vs placebo, 8 semaines). Un prélèvement sanguin et urinaire et un test d’effort ont été pratiqués avant et en fin de traitement, avec une biopsie musculaire 4 jours avant le second test d’effort. Les 12 sujets traités par simvastatine ont été séparés en deux sous-groupes selon la médiane de l’élévation des CK sous traitement (36UI/l). Les paramètres évalués ont comporté : bilan hépatique, isoprostanurie, VitC, lactates/pyruvates à l’exercice, respiration mitochondriale (pyruvate et roténone/succinate) et caractéristiques des sparks calciques sur la biopsie. Résultats Le traitement par simvastatine a induit une élévation significative des ASAT (3.38 ± 5.68 vs – 1.15 ± 4.32UI/l, p < 0,001), des CK (99.1 ± 189.3 vs – 24.3 ± 48.3UI/l, p = 0,01) et une tendance à l’élévation de l’isoprostanurie (193 ± 408 vs 12 ± 53 pmol/mmolcréat, p = 0,09), sans modification de la respiration mitochondriale, du rapport lactate/pyruvate ou des sparks calciques. Dans le sous-groupe statine-forte variation des CK vs respectivement le sous-groupe statine-faible variation de CK et le groupe placebo, on observait : une altération de la respiration mitochondriale avec diminution de la Vmax roténone/succinate (4.10 ± 1.01 vs 5.78 ± 2.49 μmolO2/min/g, p < 0,05 et vs 6.38 ± 1.90, p < 0,05), une augmentation du taux plasmatique de vitC (38.8 ± 30,5 vs – 2.7 ± 20,5mmol/l, p < 0,05 et vs – 0,4 ± 26.1, p < 0,05), une augmentation de l’amplitude des sparks (0,67 ± 0,04 vs 0,51 ± 0,05, p < 0,05 et vs 0,58 ± 0,03, p = 0,08) et une tendance à l’augmentation de leur fréquence (42.3. ± 6.3vs25.3 ± 9.4/104s/μm, NS et vs 28.6 ± 4.9, p = 0,10). Conclusion La myopathie induite par les statines pourrait être liée à des altérations de la respiration mitochondriale et de l’homéostasie calcique musculaire.
    Diabetes & Metabolism 03/2012; 38:A18–A19. DOI:10.1016/S1262-3636(12)71052-2 · 3.27 Impact Factor
  • Eric Renard · Jerome Place · Martin Cantwell · Hugues Chevassus · Cesar C Palerm ·

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    ABSTRACT: Fenugreek seeds (Trigonella foenum-graecum L.) have long been used as a herbal medicine for treating metabolic and nutritive dysfunctions. They have been shown to modulate feeding behaviour in animals. We have recently observed a selective decrease in fat consumption in healthy normal weight volunteers treated with a hydro-alcoholic seed extract. However, strong clinical data on the effects of fenugreek seeds on energy intake are lacking, especially in overweight individuals. The aim of our study was to investigate the effects of a repeated administration of a fenugreek seed extract on the eating behaviour of overweight subjects. Thirty-nine healthy overweight male volunteers completed a 6-week double-blind randomized placebo-controlled parallel trial of a fixed dose of a fenugreek seed extract. Main endpoints were energy intake (dietary records and meal test), weight, fasting and post-absorptive glucose and insulin, appetite/satiety scores and oxidative parameters. Daily fat consumption, expressed as the ratio fat reported energy intake/total energy expenditure (fat-REI/TEE), was significantly decreased in our overweight subjects administered the fenugreek seed extract relative to those receiving the placebo (fat-REI/TEE 0.26 +/- 0.02 vs. 0.30 +/- 0.01, respectively; P = 0.032). We also observed a significant decrease in the insulin/glucose ratio in subjects treated with fenugreek seed extract relative to the placebo group (0.89 +/- 0.09 vs. 1.06 +/- 0.10 mUI mmol(-1), respectively; P = 0.044). No significant effect was observed on weight, appetite/satiety scores or oxidative parameters. The repeated administration of a fenugreek seed extract slightly but significantly decreased dietary fat consumption in healthy overweight subjects in this short-term study.
    European Journal of Clinical Pharmacology 12/2009; 66(5):449-55. DOI:10.1007/s00228-009-0770-0 · 2.97 Impact Factor
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    Eric Renard · Jerome Place · Martin Cantwell · Hugues Chevassus · Cesar C Palerm ·
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    ABSTRACT: Attempts to build an artificial pancreas by using subcutaneous insulin delivery from a portable pump guided by an subcutaneous glucose sensor have encountered delays and variability of insulin absorption. We tested closed-loop intraperitoneal insulin infusion from an implanted pump driven by an subcutaneous glucose sensor via a proportional-integral-derivative (PID) algorithm. Two-day closed-loop therapy (except for a 15-min pre-meal manual bolus) was compared with a 1-day control phase with intraperitoneal open-loop insulin delivery, according to randomized order, in a hospital setting in eight type 1 diabetic patients treated by implanted pumps. The percentage of time spent with blood glucose in the 4.4-6.6 mmol/l range was the primary end point. RESULTS During the closed-loop phases, the mean +/- SEM percentage of time spent with blood glucose in the 4.4-6.6 mmol/l range was significantly higher (39.1 +/- 4.5 vs. 27.7 +/- 6.2%, P = 0.05), and overall dispersion of blood glucose values was reduced among patients. Better closed-loop glucose control came from the time periods excluding the two early postprandial hours with a higher percentage of time in the 4.4-6.6 mmol/l range (46.3 +/- 5.3 vs. 28.6 +/- 7.4, P = 0.025) and lower mean blood glucose levels (6.9 +/- 0.3 vs. 7.9 +/- 0.6 mmol/l, P = 0.036). Time spent with blood glucose <3.3 mmol/l was low and similar for both investigational phases. Our results demonstrate the feasibility of intraperitoneal insulin delivery for an artificial beta-cell and support the need for further study. Moreover, according to a semiautomated mode, the features of the pre-meal bolus in terms of timing and amount warrant further research.
    Diabetes care 10/2009; 33(1):121-7. DOI:10.2337/dc09-1080 · 8.42 Impact Factor
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    ABSTRACT: Fenugreek seeds (Trigonella foenum-graecum L.) are an old herbal remedy used to treat metabolic and nutritive dysfunctions. They have been shown to modulate feeding behaviour in animals, but strong clinical data are lacking. The aim of this study was to investigate the effects of a repeated administration of a fenugreek seed extract on energy intake and eating behaviour in healthy human volunteers. Twelve healthy male volunteers completed a double-blind randomized placebo-controlled three-period cross-over trial of two different doses of a fenugreek seed extract (588 and 1176 mg). The three 14-day treatment periods were separated by a 14-day washout period. The main endpoints were energy intake, assessed in volunteers under normal ambulatory and free-living conditions by a 3-day detailed dietary record and during a meal test, weight, fasting glucose level, insulin and lipid profile, visual analogue scale scores of appetite/satiety and blood glucose and insulin levels measured repeatedly after a standardized breakfast. Daily fat consumption was significantly decreased by the higher dose of fenugreek seed extract [3.73 vs. 4.51 MJ day(-1), -17.3% vs. placebo, 95% confidence interval (CI) -1.51 to -0.05, n = 12, P = 0.038]. This specific reduction tended to lower the total energy intake (9.97 vs. 11.29 MJ day(-1), -11.7% vs. placebo, 95% CI -2.91 to 0.26, n = 12, P = 0.094). No significant effect was observed on the other nutrients or other endpoints. The repeated administration of a fenugreek seed extract specifically decreases dietary fat consumption in humans which, given the traditional use of the plant, constitutes a novel result.
    European Journal of Clinical Pharmacology 10/2009; 65(12):1175-8. DOI:10.1007/s00228-009-0733-5 · 2.97 Impact Factor
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    ABSTRACT: Healthy volunteers must undergo a medical examination before enrollment in a clinical trial. An increasing number of trials include specific populations designed to match the target populations of the drugs tested. Our study aimed at evaluating which investigations are the most appropriate in different sub-populations of healthy volunteers. Data from 350 healthy volunteers who attended our Research Center from 1997 to 2004 were retrospectively analysed. Volunteers were distributed into five sub-populations: young men, senior men, overweight men, young women, postmenopausal women. The screening procedure comprised a review of medical history, physical examination, electrocardiogram and laboratory tests. Ineligibility criteria were classified as non-medical causes, protocol specific medical causes and non-specific medical causes. A total of 148 subjects (42%) were not-eligible, mainly because of non-specific medical causes (111 subjects), including abnormal medical history (34.5% of all ineligibilities). Blood pressure abnormalities were frequent in all sub-populations except young women. Electrocardiographic abnormalities led to ineligibility of only five overweight men and one menopausal woman. Abnormal laboratory tests accounted for 19.6% of ineligibilities. In senior subjects and overweight men, serologies, liver function tests and lipid profile contributed importantly to the selection process. Low red cells count was the most frequent laboratory abnormality in young women. Erythrocyte sedimentation rate, phosphocalcic metabolism and standard clotting tests led to frequent insignificant and non-contributive abnormalities. Our study confirms that a complete review of medical history is essential and determines the major part of ineligibilities. Complementary laboratory tests are always needed and may be adjusted to the population considered.
    Fundamental and Clinical Pharmacology 09/2009; 24(1):121-7. DOI:10.1111/j.1472-8206.2009.00727.x · 2.12 Impact Factor
  • E. Renard · M. Cantwell · H. Chevassus · C. Palerm ·
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    ABSTRACT: Introduction L’administration intra-péritonéale (IP) d’insuline offre une pharmacocinétique plus physiologique que la voie sous-cutanée (SC). L’évaluation du bénéfice de son asservissement via un algorithme à un capteur de glucose SC chez des malades diabétiques de type 1 (DT1) justifie la présente étude. Patients et méthodes Huit patients DT1 (7H/1F, âge : 60 ± 9 ans, durée DT1 : 32 ± 15 ans, HbA1c : 6,8 ± 1,0 %) traités par pompe à insuline implantée (modèle 2007D, Medtronic) depuis 8,5 ± 7,4 ans ont réalisé au CIC, selon un ordre randomisé, une épreuve d’insulinothérapie en boucle fermée de 48 h (IBF) puis une épreuve-contrôle en boucle ouverte de 24 h (IBO). Durant l’IBF, le débit d’insuline était réglé par un algorithme de type PID selon les données continues d’un capteur SC (MMT-7002, Medtronic) sauf qu’un bolus était programmé 15 min avant les repas. Durant l’IBO, le patient adaptait la pompe selon 7 glycémies capillaires. La glycémie et l’insulinémie ont été dosées par heure de 8 à 22 h, par 2 heures de 22 à 8 h, et par 20 min au cours des 2 heures qui suivaient les repas. Le critère de jugement principal était le taux de temps passé avec une glycémie entre 4,4 et 6,6 mmol/L (%TPG 4,4-6,6) au cours de chaque épreuve. Résultats Durant l’IBF, le %TPG 4,4-6,6 était significativement plus élevé : 39,1 ± 4,5 versus 27,7 ± 6,2 (p = 0,05) alors que la glycémie moyenne était similaire à celle de l’IBO : 7,4 ± 0,4 versus 7,6 ± 0,7 mmol/L. L’amélioration concernait les phases extra-prandiales avec un %TPG 4,4-6,6 de 46,3 ± 5,3 versus 28,6 ± 7,4 (p = 0,025), un %TPG > 6,6 mmol/L de 42,0 ± 6,0 versus 53,8 ± 8,4 (p = 0,036) et une glycémie moyenne de 6,9 ± 0,3 versus 7,9 ± 0,6 mmol/L (p = 0,036), mais pas les phases prandiales (repas + 2 h). La dispersion inter-individuelle post-prandiale était cependant moindre lors de l’IBF. De même, la dispersion inter-individuelle nocturne (22-8 h) était plus faible pour un %TPG 4,4-6,6 et une glycémie moyenne similaires. L’incidence des hypoglycémies était faible et similaire. Conclusion Le meilleur contrôle glycémique obtenu lors d’une perfusion IP d’insuline liée à un capteur SC via un algorithme PID valide la faisabilité, l’efficacité et la sécurité de cette approche comme un nouveau modèle possible de pancréas artificiel. La difficulté du contrôle post-prandial promeut une boucle partiellement ouverte, avec nécessité d’améliorer l’apport d’insuline lors de cette phase.
    Diabetes & Metabolism 03/2009; 35. DOI:10.1016/S1262-3636(09)71755-0 · 3.27 Impact Factor
  • J.L. Faillie · H. Chevassus · I. Gabillaud · C. Kahn · P. Petit · F. Galtier ·
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    ABSTRACT: En raison du coût élevé des analyseurs de glucose, les appareils d’autocontrôle glycémique sont parfois utilisés lors d’explorations métaboliques. Cependant, lorsqu’ils sont utilisés pour adapter les débits de perfusion lors d’un clamp, l’erreur de mesure peut induire des écarts sur les débits perfusés. Notre objectif était donc de comparer les glycémies obtenues avec 3 méthodes (biochimie, analyseur de glucose, appareil d’autocontrôle) et les débits correspondants.Matériels et MéthodesLors de 13 clamps hyperglycémiques (10 mmol/L), 11 glycémies ont été mesurées par analyseur de glucose (2 300 Stat Plus, System Industry), appareil d’autocontrôle (medisense optium Xceed), et dosées en laboratoire de biochimie. Au cours du clamp, les débits de perfusion de glucosé 30 % ont été calculés d’après l’analyseur. Les valeurs des autres méthodes ont ensuite été utilisées pour calculer le débit théorique idéal (valeur de biochimie) et le débit donné par l’appareil d’autocontrôle. L’analyse statistique (logiciel SAS pour Windows version 9) a utilisé des tests non paramétriques de comparaison de mesures appariées (Friedman et Wilcoxon). Les médianes des différences entre les méthodes sont présentées avec leurs percentiles 5 % et 95 %.RésultatsAu total, 128 glycémies ont été comparés. Il existe une différence significative globale entre les trois méthodes (p = 0,004). Pour l’analyseur, la médiane des différences avec la biochimie est de –0,06 mmol/L (P5 = −1,37, P95 = 1 ; p = 0,36) pour les glycémies > 7 mmol/L (n = 116), et de –0,59 (P5 = − 1,02, P95 = −0,13 ; p < 0,001) pour les glycémies ≤ 7 mmol/L (n = 12). Avec l’appareil d’autocontrôle, la médiane des différences avec la biochimie est de 0,16 mmol/L (P5 = -1,46, P95 = 1,57 ; p = 0,18), non significative pour les glycémies ≤ 7 ou > 7 mmol/L. La comparaison des débits ne montre pas de différence entre les 3 méthodes (p = 0,61). Les médianes des différences (biochimieanalyseur) et (biochimie-autocontrôle) sont respectivement 1,5 mmol/L (P5 = –51,5 ; P95 = 71 ; p = 0,27) et –7 mmol/L (P5 = −73 ; P95 = 84 ; p = 0,60).Conclusion Pour le calcul de débit, les résultats de l’appareil d’autocontrôle semblent être équivalents à l’analyseur. Considérant ses autres avantages (rapidité, coût faible), il semble acceptable de l’utiliser pour un clamp hyperglycémique.
    Diabetes & Metabolism 03/2008; 34:H91. DOI:10.1016/S1262-3636(08)73095-7 · 3.27 Impact Factor
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    A Farret · H Chevassus · B Roux · P Petit · F Galtier ·
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    ABSTRACT: In addition to the improvement in insulin sensitivity, it has been shown that thiazolidinediones modulate beta cell function and insulin clearance in type 2 diabetic subjects. However, interactions between all these actions, and confounding factors due to co-morbidities and co-treatments in diabetic individuals, complicate the identification of specific effects. The aim of this pilot study was to investigate the potential acute effects of rosiglitazone on beta cell function and insulin sensitivity by the hyperglycaemic clamp technique in healthy volunteers. Twelve healthy men were included in a randomised, double-blind crossover study. Rosiglitazone (8 mg) or placebo was given orally 45 min before the hyperglycaemic clamp (10 mmol/l for 2 h). The second phase of the insulin response was significantly decreased by rosiglitazone: 13,066 +/- 1,531 vs 16,316 +/- 2,813 pmol l(-1) 110 min in controls (p < 0.05), without change in the first phase. Serum C-peptide was not modified. Rosiglitazone treatment significantly increased insulin clearance (molar ratio of the C-peptide to insulin AUCs: 12.80 +/- 1.34 vs 11.38 +/- .33, p < 0.05) and the insulin sensitivity index (12.0 +/- 1.5 vs 8.5 +/- 1.1 micromol m(-2) min(-1) pmol(-1)l, p < 0.01). The present results show that a single dose of rosiglitazone rapidly increases insulin clearance and insulin sensitivity index in healthy volunteers, with no direct effect on insulin secretion. The precise mechanisms mediating these actions remain to be determined.
    Diabetologia 08/2007; 50(7):1384-7. DOI:10.1007/s00125-007-0682-4 · 6.67 Impact Factor
  • E Renard · G Costalat · H Chevassus · J Bringer ·
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    ABSTRACT: Restoration of long-term normal blood glucose control in diabetic patients supports the elaboration of an artificial beta cell. The possibility of implantation of the three crucial components of such a system (insulin delivery device, glucose sensor and controller) is analyzed. The Long-Term Sensor System project, aiming at a fully implantable artificial beta cell, assessed the feasibility of glucose control by the combined implantation of a pump for peritoneal insulin delivery and a central intravenous glucose sensor close to the right atrium, connected via a subcutaneous lead. It was initiated in 10 Type 1 diabetic patients in our clinic from 2000. Data obtained during this experience are reviewed and confronted to reported closed-loop trials using other approaches. No significant complication related to prolonged implantation of intravenous sensors occurred and the combined implants were well tolerated. Glucose measurement by the intravenous sensors correlated well with meter values (r=0.83-0.93, with a mean absolute deviation of 16.5%) and accuracy has been sustained for an average duration of 9 months. Uploading of pump electronics by algorithms designed for closed-loop insulin delivery allowed in-patient 48 hour-trials aiming at automated glucose control. Glucose control was similar to that reported by investigations combining subcutaneous sensors to wearable pumps for subcutaneous insulin infusion. The benefits of more physiological insulin kinetics due to intra-peritoneal delivery have been hampered by the slow response time of intravenous sensors. Although the concept of a fully implantable artificial beta cell has been validated as feasible, the limited performance in achieving glucose control requests improvements in the sensor structure to increase its longevity and decrease sensor delay.
    Diabetes & Metabolism 01/2007; 32(5 Pt 2):497-502. · 3.27 Impact Factor
  • Eric Renard · Guy Costalat · Hugues Chevassus · Jacques Bringer ·
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    ABSTRACT: We investigated the feasibility of closed loop insulin delivery by using a model based upon the coupling of an implanted insulin pump that infuses insulin by intra-peritoneal route and an intravenous enzymatic glucose sensor. Closed Loop Control (CLC) by a proportional, integral and derivative algorithm was initiated in 4 type 1 diabetic subjects, already implanted with both devices (MiniMed-Medtronic, Northridge, CA, USA), and continued for 48 hours. Three meals of 40 g and twice 80 g carbohydrates were served daily. Blood glucose was assessed every 10 minutes for the first two hours of meals and every 30 minutes otherwise. Algorithm parameters were empirically adjusted during the experiment based on antecedent blood glucose levels. CLC in one subject was stopped after 24 hours due to inadequate sensor performance. During CLC, the algorithm kept glucose within 80–240 mg/dl for 84.1% of the time. Algorithm retuning did not change the percentage of glucose >240 mg/dl but increased the percentage within the 80–120 mg/dl range during the final 24 hours. Excluding meals, glucose was
    Diabetes Research and Clinical Practice 12/2006; 74. DOI:10.1016/S0168-8227(06)70026-2 · 2.54 Impact Factor

Publication Stats

329 Citations
80.07 Total Impact Points


  • 2012-2015
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2009
    • Université de Montpellier 1
      Montpelhièr, Languedoc-Roussillon, France
    • Centre Hospitalier Universitaire de Montpellier
      • Centre d'Investigation Clinique
      Montpelhièr, Languedoc-Roussillon, France
  • 2004
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2002
    • Montpellier SupAgro
      Montpelhièr, Languedoc-Roussillon, France