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Publications (19)56.82 Total impact

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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; · 2.70 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. · 3.98 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; · 3.68 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. · 2.85 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. · 2.85 Impact Factor
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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. · 2.70 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. · 2.70 Impact Factor
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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. · 7.74 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. · 2.08 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. · 2.85 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. · 6.88 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. · 2.85 Impact Factor
  • E. Renard, G. Costalat, H. Chevassus, J. Bringer
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    ABSTRACT: But La restauration d’un contrôle glycémique normal à long terme chez les sujets diabétiques est à l’origine de l’élaboration d’une cellule bêta artificielle. La possibilité d’implantation des trois composants essentiels d’un tel système (dispositif d’administration d’insuline, capteur de glucose et module de contrôle) est analysée. Méthodes Le projet Long-Term Sensor System®, visant une cellule bêta artificielle complètement implantée, a évalué la faisabilité du contrôle glycémique par l’implantation combinée d’une pompe pour la perfusion intrapéritonéale d’insuline et d’un capteur de glucose intraveineux central à proximité de l’oreillette droite, reliés par un câble sous-cutané. Il a été commencé chez 10 diabétiques de type 1 dans notre clinique à partir de 2000. Les données issues de cette expérience font l’objet d’une revue et d’une confrontation avec les essais rapportés de fonctionnement en boucle fermée utilisant d’autres approches. Résultats Aucune complication significative liée à l’implantation prolongée des capteurs intraveineux n’est survenue et les implants combinés ont été bien tolérés. Les mesures de glucose par les capteurs intraveineux étaient bien corrélées avec les valeurs des glucomètres (r = 0,83-0,93, avec une déviation moyenne absolue de 16,5%) et l’exactitude a été maintenue sur une durée moyenne de 9 mois. La mise en place dans l’électronique des pompes d’algorithmes destinés à l’administration d’insuline en boucle fermée a permis des essais de 48 heures chez des sujets hospitalisés visant un contrôle glycémique automatisé. Le contrôle glycémique était similaire à celui rapporté par des recherches combinant des capteurs de glucose sous-cutanés à des pompes portables pour la perfusion sous-cutanée d’insuline. Les bénéfices d’une cinétique de l’insuline plus physiologique due à l’administration intrapéritonéale ont été amoindris par le temps de réponse lent des capteurs intraveineux. Conclusion Bien que le concept d’une cellule bêta artificielle complètement implantée ait été validé comme faisable, la réussite limitée dans l’obtention du contrôle glycémique requiert des améliorations dans la structure du capteur pour augmenter sa longévité et diminuer le délai de réponse du capteur.
    Diabetes & Metabolism 12/2006; 32(5):497-502. · 2.85 Impact Factor
  • Annales d Endocrinologie 10/2006; 67(5):458-459. · 0.66 Impact Factor
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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 - DIABETES RES CLIN PRACT. 01/2006; 74.
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    ABSTRACT: Nigella sativa L. 'Black cumin' (Ranunculaceae) is one of the plants commonly used in Moroccan folk medicine for treatment of various ailments including diabetes mellitus. The present study was undertaken to investigate the effect of different N. sativa seed extracts on insulin secretion. Different fractions of the seed were prepared: the defatted fraction (HR II), which was divided into two subfractions: the first (HR III) containing acidic and neutral compounds and the second (HR IV) containing basic compounds. The insulin secretory effects of these extracts were evaluated individually at different concentrations (0.01, 0.1, 1 and 5 mg/mL), in vitro in isolated rat pancreatic islets in the presence of 8.3 mmol/L glucose. The results show that addition of the defatted whole extract or of the basic subfraction of the seed in the incubation medium significantly increased glucose-induced insulin release from the islets. In the case of the acidic and neutral subfraction, the stimulatory effect was observed only for the higher concentration (5 mg/mL). However, a clear concentration-dependent increase in insulin release from isolated pancreatic islets was observed for the basic subfraction. Our data show that the antidiabetic properties of N. sativa seeds may be, at least partly, mediated by stimulated insulin release, and that the basic subfraction largely contributes to this stimulatory effect. Further phytochemical studies are underway in order to isolate the pharmacological compound(s) responsible for the insulinotropic effect of N. sativa seeds.
    Fundamental and Clinical Pharmacology 11/2004; 18(5):525-9. · 2.08 Impact Factor
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    ABSTRACT: The present study aimed at investigating in healthy volunteers the effects of diazepam and clonazepam on beta-cell function, insulin sensitivity and glucose effectiveness based on the frequently sampled intravenous (0.5 gkg-1) glucose tolerance test with minimal-model analysis. The study was designed as a double-blind, placebo-controlled, cross-over clinical trial. Diazepam (10 mg) and clonazepam (1 mg) were infused during 30 min to 15 male subjects with a mean age of 22 years (range: 20-29), after informed consent was given. Benzodiazepines were assayed by capillary gas chromatography with electron capture, insulin by radioimmunoassay and glucose by the enzymatic glucose oxidase method. Both benzodiazepines induced significant psychotropic effects. The acute insulin responses (AIR) were significantly and negatively correlated with the clonazepam plasma concentrations (r = -0.609, P < 0.05, n = 14). However, the mean AIR was not significantly different between the benzodiazepine-treated subjects and the controls. In addition, the parameters of glucose assimilation were significantly decreased as compared with placebo in the subgroup of 7 subjects with plasma clonazepam concentrations higher than 6.0 ng ml-1 (median and lower limit of effective therapeutic concentrations): 1.37 +/- 0.3 versus 2.84 +/- 0.60 x 10(-2)min-1 (P = 0.028) for the coefficient of glucose tolerance (Kg), 2.18 +/- 0.29 versus 3.71 +/- 0.89 x 10(-4)microUml-1min-1 (P = 0.018) for insulin sensitivity (Si) and 1.80 +/- 0.39 versus 3.59 +/- 0.71 x 10(-2)min-1 (P = 0.028) for glucose effectiveness at basal insulin (Sg). These parameters were not significantly modified when diazepam was administered; plasma levels of this drug however, were below the effective therapeutic concentrations (300 ng ml-1) from min 15 after the end of the perfusion. The present results suggest that a benzodiazepine, in particular clonazepam, may alter insulin secretion and insulin sensitivity after a single administration in healthy volunteers.
    BMC Clinical Pharmacology 04/2004; 4:3. · 1.36 Impact Factor
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    ABSTRACT: Adenine nucleotides stimulate insulin secretion by binding to P2 receptors of the pancreatic beta-cells; the stimulus-secretion coupling is not yet clearly established and may depend on the receptor subtype. The aim of the present study was to further investigate the mechanism whereby P2Y receptor agonists enhance glucose-induced insulin secretion. Experiments were performed in rat pancreatic islets and in the INS-1 secreting cell line in the presence of a slightly stimulating glucose concentration (8.3 mmol/l). In isolated islets, the P2Y receptor agonist ADPbetaS (50 micromol/l) induced a significant fivefold increase in the cyclic AMP (cAMP) content, from 43.4+/-3.7 fmol/10 islets in controls to 210.6+/-12.0; it still induced a 4.5-fold increase in cAMP content in the absence of calcium. In another series of experiments, ADPbetaS (50 micromol/l) significantly increased glucose-induced insulin secretion from 7.7+/-0.6 ng/3 islets in controls to 11.2+/-1.0. The adenylyl cyclase inhibitor SQ 22,536 (9-[tetrahydro-2-furanyl]-9 H-purin-6-amine; 100 micromol/l), which was ineffective alone, completely prevented the stimulating effect of ADPbetaS. In a set of experiments in which ADPbetaS increased glucose-induced insulin secretion from 10.0+/-0.7 ng/3 islets to 12.6+/-0.8, the inhibitor of cAMP-dependent protein kinase, TPCK (tos-phe-chloromethylketone; 3 micromol/l), which was ineffective alone, also prevented the stimulating effect of ADPbetaS. In incubated INS-1 cells, the P2Y receptor ligand ATPalphaS increased significantly both the content of cAMP and the release of insulin, in a concentration-dependent manner in the range of 50-150 micromol/l; the insulin release was significantly correlated with the cAMP content. In conclusion, the present results show that P2Y receptor agonists, ADPbetaS and ATPalphaS, amplify glucose-induced insulin secretion by activating beta-cell adenylyl cyclase and the subsequent cAMP/protein kinase A signaling pathway.
    Archiv für Experimentelle Pathologie und Pharmakologie 12/2002; 366(5):464-9. · 2.36 Impact Factor
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    ABSTRACT: To investigate the effects of glutamate on insulin secretion and glucose tolerance in humans. Monosodium (L)-glutamate (10 g) was given orally in a double-blind placebo-controlled cross-over study to 18 healthy volunteers, aged 19-28 years, with an oral (75 g) glucose load. The 75 min insulin response (AUC(0,75 min)), up to tmax of glutamate kinetics, was significantly correlated with the AUC(0,75 min) of glutamate concentrations (r=0.485, P=0.049). Glucose tolerance was not affected. Oral (L)-glutamate enhances glucose-induced insulin secretion in healthy volunteers in a concentration-dependent manner.
    British Journal of Clinical Pharmacology 07/2002; 53(6):641-3. · 3.69 Impact Factor