Saint-Antoine-du-Rocher, France
Saint-Antoine-du-Rocher, France

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Doucet J.,University of Rouen | Le Floch J.-P.,Service de diabetologie endocrinologie | Bauduceau B.,Service dendocrinologie | Verny C.,Service de gerontologie
Diabetes and Metabolism | Year: 2012

Aims: The GERODIAB study is the first French multicentre, prospective, observational study that aims, through a 5-year cohort follow-up, to evaluate the link between glycaemic control and morbidity/mortality of type 2 diabetic (T2D) patients aged 70 years and older. This first report describes the study population at inclusion. Patients and methods: A total of 987 T2D autonomous patients, aged ≥ 70 years, were recruited between June 2009 and July 2010 at 56 investigator centres. Their general parameters, diabetes characteristics and standard geriatric parameters were recorded. Results: The patients' mean age was 77±5 years, with 65.2% aged 75 years or more. The mean BMI was close to 30kg/m2. Hypertension was found in 89.7% of patients, and 85.0% had at least one cholesterol abnormality. The mean duration of the diabetes was around 18 years, and the mean HbA1c level was about 7.5%. During the previous six months, 33.6% of patients had experienced one or several hypoglycaemias. Also, 26% of patients presented with diabetic retinopathy, 37.3% had a GFR<60mL/min, 31.2% had coronary insufficiency, 10.1% had heart failure, 15.8% had cerebrovascular involvement and 25.6% had peripheral vascular disease of the lower extremities. In addition, 30.5% of patients had orthostatic hypotension, 12.4% had malnutrition and 28.8% had cognitive impairment, all of which were often diagnosed at inclusion. Three-quarters of patients were taking an oral antidiabetic drug and nearly six in every 10 patients were using insulin. Conclusion: This population can be considered representative of elderly, autonomous T2D patients, and its follow-up should clarify the link between glycaemic control and mortality/morbidity. © 2012 Elsevier Masson SAS.


Mayaudon H.,Service dendocrinologie | Miloche P.-O.,Deuxieme regiment de dragons | Bauduceau B.,Service dendocrinologie
Diabetes and Metabolism | Year: 2010

Aim: The current sudomotor function tests are too time-consuming to be used for diabetic patients in daily practice. EZSCAN is a new, patented technology that measures electrochemical skin conductance (ESC) through reverse iontophoresis and chronoamperometry. The aim of the present study was to assess the sensitivity, specificity and reproducibility of the method in type 2 diabetic patients in comparison to control subjects with no risk of diabetes. Methods: A total of 133 type 2 diabetic patients and 41 control subjects were tested. Participants placed their hands and feet on nickel electrodes, and an incremental low direct current was applied to the anode for 2. min. ESC was calculated from the resulting voltage and generated current. ESC diagnostic accuracy was analyzed by ROC curve modeling, and reproducibility was assessed using Bland-Altman analysis. Results: The ESC of hands and feet was significantly reduced in diabetic patients (53±16 μSi and 67± 14 μSi, respectively) compared with control subjects (68±16. μSi and 80±7. μSi, respectively; P<0.0001). ESC values had a sensitivity of 75% and specificity of 100%, with an area under the ROC curve of 0.88 at a threshold of 50% on the EZSCAN scale. Coefficients of variation in hand and foot measurements were 15 and 7%, respectively. Conclusion: The good sensitivity, specificity and reproducibility of EZSCAN make it a feasible alternative for assessing sudomotor dysfunction, a clinical manifestation of autonomic neuropathy in diabetic patients. The test takes. <3. min to perform, and requires neither special patient preparation nor medical personnel training. Objectif: Les tests destinés à évaluer la fonction sudorale sont trop longs pour pouvoir être utilisés en pratique courante chez le diabétique. EZSCAN est une nouvelle méthode brevetée qui mesure la conductance éléctrochimique de la peau (CEP) en utilisant l'iontophorèse inverse et la chronoampéromètrie. Le but de l'étude était d'évaluer la sensibilité, la spécificité et la reproductivité de la méthode utilisée chez des diabétiques de type 2 comparativement à des non-diabétiques. Méthodes: Cent trente trois patients DT2 et 41 sujets témoins on été testés. Il était demandé aux participants de placer leurs mains et leurs pieds sur des électrodes de nickel et un faible courant continu était appliqué sur l'anode durant 2. min. La CEP est calculée à partir de la tension résultante et du courant généré. La performance diagnostic de EZSCAN a été analysée au moyen d'une courbe ROC. La reproductibilité a été évaluée par un test de Bland et Altman. Résultats: La conductance électrochimique des mains et des pieds étaient significativement diminuées chez les patients DT2 (53±16 et 67±14. μSi, respectivement) par comparaison aux sujets témoins (68±16 et 80±7. μSi, P<0,0001). La sensibilité et la spécificité de la mesure de la conductance électrochimique étaient respectivement de 75 et 100 % avec une aire sous la courbe de 0,88 en se fondant sur le seuil de 50 % sur l'échelle EZSCAN. Les coefficients de variations pour les mains et pour les pieds chez les patients DT2 étaient respectivement de 15 et 7 %. Conclusion: La bonne sensibilité, spécificité et reproductibilité de EZSCAN en font une alternative crédible pour évaluer les perturbations de la fonction sudorale, manifestation clinique de la neuropathie du système végétatif chez les patients diabétiques. Ce test ne requiert ni préparation spéciale, ni entraînement du personnel médical et nécessite pour la mesure moins de trois minutes. © 2010 Elsevier Masson SAS.


Obesity appears multifactorial but some cases may involve viral infections. Several species of viruses have been linked to obesity in chickens, mice and monkeys. In humans, only adenovirus-36 (Ad-36) is strongly associated. Further studies are still needed to confirm a causal relationship and to try to identify possible predisposing factors to the effects of Ad-36. Effects of Ad-36 pass by the expression of viral gene E4Orfl promoting the differentiation of fat stem cells. Future progress in understanding the cellular mechanisms underlying the relationship between the Ad-36 (and other viruses) and obesity can lead to identify new targets for the prevention and the treatment.


Carney J.A.,Mayo Medical School | Gaillard R.C.,University of Lausanne | Bertherat J.,Service dEndocrinologie | Stratakis C.A.,U.S. National Institutes of Health
American Journal of Surgical Pathology | Year: 2010

We present the pathologic findings in the adrenal glands of 4 patients, aged 10 to 38 years, with Cushing syndrome and germline inactivating mutations of the gene PDE11A4 that encodes phosphodiesterase11A4. The gene is expressed in the adrenal cortex and catalyses the hydrolysis of cyclic adenosine monophosphate and cyclic guanosine monophosphate. Two of the patients were mother and daughter; the third had no affected relative; the fourth patient inherited the mutation from her father. Three of the group, including the mother and daughter, had the same pathology, primary pigmented nodular adrenocortical disease, a disorder known to be caused by inactivating mutations of the PRKAR1A gene. In these cases, the adrenal glands were small and the pathologic change was deep in the cortex in which numerous pigmented micronodules developed. In the remaining patient, the glands were slightly enlarged primarily owing to a diffuse hyperplasia of the superficial cortex that extended into the epi-adrenal fat. © 2010 Lippincott Williams & Wilkins.


Epidemiological studies among diabetic populations have clearly shown a positive association between hyperglycemia and the risk for cardiovascular events independently of other riskfactors. Moreover, manypathophysiological data indicate the deleterious role of hyperglycemia on the arterial wall through promotion of inflammation and oxidation, and through the local accumulation of Advanced Glycosylation End products (AGE). However, the demonstration of the cardiovascular benefit secondary to the reduction of hyperglycemia is not clear. Indeed, in the UKPDS, VADT and ADVANCE trials no significant reduction of the risk for major cardiovascular events has been observed among the patients enrolled in the "intensive treatment of diabetes" group. However, the prolonged follow-up of the patients from UKPDS, VADT and ACCORD, in type 2 diabetes, and from DCCT/EDIC, in type 1 diabetes, has clearly shown a significant reduction of major cardiovascular events in the patients initially enrolled in the "intensive treatment" groups. Thus, the present data seems to indicate a real cardiovascular benefit secondary to the reduction of hyperglycemia that is "late". This rather "late" effect could partly be due to the prolonged modification of the arterial wall promoted by the local accumulation of AGE. © 2015 Elsevier Masson SAS - Tous droits réservés.


Giusti V.,Service dEndocrinologie
Revue Medicale Suisse | Year: 2010

Bariatric surgery techniques can usually increase either sensitivity or insulin resistance, acting on three different levels: decrease of food intake, malabsorption and modifications of entero-insulaire axis activity. This latter is taken into account in order to develop a new protocol to obtain diabetes remission without Important weight loss and nutritional deficiencies. Preliminary results are interesting but they come from very short time studies with few patients. Moreover, complications rate is at present very high. Knowing better gastrointestinal mechanisms of diabetes control and especially incretins role is absolutely necessary before identifying surgery as a true metabolic treatment.


Carney J.A.,Mayo Medical School | Libe R.,Service dEndocrinologie | Bertherat J.,Service dEndocrinologie | Young W.F.,Mayo Medical School
American Journal of Surgical Pathology | Year: 2014

The original 4 patients with Cushing syndrome who underwent bilateral adrenalectomy for primary pigmented nodular adrenocortical disease were followed up for an average of 31 years to determine whether they or any of their primary relatives had developed Carney complex or its components. None had. Three of the patients were alive and well; the fourth had died of an unrelated condition. All the adrenal glands contained multiple small, black or brown cortical nodules, up to 4 mm in diameter. The extracapsular extension of the micronodules was limited to the immediate pericapsular adipose tissue and was not considered evidence of low-grade malignancy. Immunocytochemically, the nodules were positive for synaptophysin, inhibin-A, and melan A and negative for vimentin and CD56. Ki-67 antibody stained the cytoplasm of cells in the micronodules but not that of the atrophic cortical cells. The 4 patients had the PRKAR1A deletion that has been associated with the isolated form of primary pigmented nodular adrenocortical disease. © 2014 by Lippincott Williams and Wilkins.


Ruiz J.,Service dEndocrinologie
Revue Medicale Suisse | Year: 2013

The new recommendations on the pharmacological treatment of type 2 diabetes have introduced two important changes. The first is to have common strategies between European and American diabetes societies. The second, which is certainly the most significant, is to develop a patient centred approach suggesting therapies that take into account the patient's preferences and use of decision support tools. The individual approach integrates six factors: the capacity and motivation of the patient to manage his illness and its treatment, the risks of hypoglycemia, the life expectancy, the presence of co-morbidities and vascular complications, as well as the financial resources of the patient and the health care system. Treatment guidelines for cardiovascular risk reduction in diabetic remains the last point to develop.


Ratziu V.,Hopital Pitie Salpetriere | Ratziu V.,French Institute of Health and Medical Research | Charlotte F.,Laboratoire dAnatomie Pathologique | Bernhardt C.,Hopital Pitie Salpetriere | And 6 more authors.
Hepatology | Year: 2010

Short-term trials of glitazones in nonalcoholic steatohepatitis (NASH) yielded controversial histological results. Longer treatment might result in additional improvement. After a 1-year randomized trial, 53 patients underwent a control liver biopsy and were enrolled in an open-label extension trial of rosiglitazone (RSG), 8 mg/day for 2 additional years. In all, 44 completed the extension phase including 40 with a third liver biopsy. Of these, 22 received placebo (PLB) in the randomized phase (PLB-RSG), and 18 RSG (RSG-RSG). During the 2-year extension phase serum insulin decreased by 26%, homeostasis model assessment (HOMA) by 30%, and alanine aminotransferase (ALT) by 24%. However, there was no significant change in the mean NASH activity score (NAS) (3.8 ± 2.11 versus 3.68 ± 1.8), ballooning score, fibrosis stage (1.76 ± 1.18 versus 1.85 ± 1.19), or area of fibrosis by micromorphometry (4.43% ± 0.68 to 5.54% ± 0.68). In the PLB-RSG group steatosis significantly decreased after 2 years of RSG (median decrease of 15%); in the RSG-RSG group, after an initial decline in the first year of 20%, 2 additional years of RSG did not result in further improvement. Likewise, there was no improvement in the NAS score, ballooning, intralobular inflammation, fibrosis stage, or area of fibrosis with 2 additional years of RSG in the RSG-RSG group. Conclusion: Rosiglitazone has a substantial antisteatogenic effect in the first year of treatment without additional benefit with longer therapy despite a maintained effect on insulin sensitivity and transaminase levels. This suggests that improving insulin sensitivity might not be sufficient in NASH and that additional targets of therapy for liver injury should be explored. Copyright © 2009 by the American Association for the Study of Liver Diseases.


Insulin treatment is associated with two important and frequent side effects: hypoglycemia and weight gain. Weight gain is in contradiction with the physiological central effect of insulin which leads to decreased food intake like leptin. However, decreased urinary caloric loss due to better glycemic control, prevention and correction of hypoglycemia, the anabolic effect of insulin and the possible central resistance to insulin explain the observed weight gain. Insulin is often necessary when oral antidiabetic treatment fails; the physician and the patient need to remain alert to minimize the side effects through adequate insulin regimen and life style.

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