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OBJECTIVES: Ever since the first research on barriers to physical activity (PA) highlighting fear of hypoglycemia as a major barrier, many studies have attempted to understand their demographic and behavioural determinants. However, no research has been conducted on whether these perceived barriers toward PA are based on real-life-experienced adverse glycemic effects of exercise. METHODS: Sixty-two adults and 53 children/adolescents living with type 1 diabetes along with their parents completed the Barriers to Physical Activity in Type 1 Diabetes-1 (BAPAD-1) questionnaire on barriers to PA. Continuous glucose-monitoring data were collected during 1 week of everyday life for 26 adults and 33 children/adolescents. Multiple linear regressions were used to explore links between BAPAD-1 scores and glycemic excursions experienced during and after everyday-life self-reported PA sessions, controlling for behavioural (accelerometry) and demographic confounders. RESULTS: In children/adolescents, the more time spent in hypoglycemia on nights after PA sessions, the more they reported hypoglycemic risk as a barrier (ß=+0.365, p=0.034). Conversely, in adults, the higher the proportion of PA sessions accompanied by a drop in blood glucose, the less hypoglycemia was a barrier (ß=-0.046, p=0.004). In parents, BAPAD-1 scores were unrelated to children/adolescents' everyday-life exercise-induced hypo/hyperglycemia. CONCLUSIONS: In children/adolescents, fear of hypoglycemia was predominant in those exposed to nocturnal hypoglycemia associated with PA sessions. In adults, fewer barriers may mean they accept a bigger drop in their glycemia during PA. This shows the importance of finding and promoting age-specific solutions to prevent exercise-induced hypoglycemia.

Patient: Female, 76 Final Diagnosis: Right upper lung tumor with severe pulmonary hypertension Symptoms: Shortness of breath Medication: — Clinical Procedure: Ecective bronxhoscopy • robotic right upper lobectomy • thoracic lymphadenectomy Specialty: Anesthesiology Objective: Rare co-existance of disease or pathology Background: It is very challenging for anesthesiologists to manage patients with pulmonary hypertension undergoing general anesthesia for elective or emergent surgeries. Case Report: We present a patient with severe pulmonary hypertension going through a major robotic thoracic surgery. Conclusions: A goal-directed anesthesia management algorithm based on serial stroke volume (SV) values obtained from FloTrac (Edwards Lifesciences, LLC.) minimally invasive arterial pressure sensor was utilized in an attempt to reduce the anesthetic and surgical risk associated with severe pulmonary hypertension.

Type 1 diabetes mellitus (T1DM) is associated with a high risk of cardiovascular (CV) complications, even after controlling for traditional CV risk factors. Therefore, determinants of the residual increased CV morbidity and mortality remain to be discovered. This prospective cohort of people living with T1DM in France (SFDT1) will include adults and children aged over six years living with T1DM, recruited throughout metropolitan France and overseas French departments and territories. The primary objective is to better understand the parameters associated with CV complications in T1DM. Clinical data and biobank samples will be collected during routine visits every three years. Data from connected tools, including continuous glucose monitoring, will be available during the 10-year active follow-up. Patient-reported outcomes, psychological and socioeconomic information will also be collected either at visits or through web questionnaires accessible via the internet. Additionally, access to the national health data system (Health Data Hub) will provide information on healthcare and a passive 20-year medico-administrative follow-up. Using Health Data Hub, SFDT1 participants will be compared to non-diabetic individuals matched on age, gender, and residency area. The cohort is sponsored by the French-speaking Foundation for Diabetes Research (FFRD) and aims to include 15,000 participants.

Objective Male sex is one of the determinants of severe coronavirus diseas-e-2019 (COVID-19). We aimed to characterize sex differences in severe outcomes in adults with diabetes hospitalized for COVID-19. Methods We performed a sex-stratified analysis of clinical and biological features and outcomes (i.e. invasive mechanical ventilation (IMV), death, intensive care unit (ICU) admission and home discharge at day 7 (D7) or day 28 (D28)) in 2380 patients with diabetes hospitalized for COVID-19 and included in the nationwide CORONADO observational study (NCT04324736). Results The study population was predominantly male (63.5%). After multiple adjustments, female sex was negatively associated with the primary outcome (IMV and/or death, OR: 0.66 (0.49–0.88)), death (OR: 0.49 (0.30–0.79)) and ICU admission (OR: 0.57 (0.43–0.77)) at D7 but only with ICU admission (OR: 0.58 (0.43–0.77)) at D28. Older age and a history of microvascular complications were predictors of death at D28 in both sexes, while chronic obstructive pulmonary disease (COPD) was predictive of death in women only. At admission, C-reactive protein (CRP), aspartate amino transferase (AST) and estimated glomerular filtration rate (eGFR), according to the CKD-EPI formula predicted death in both sexes. Lymphocytopenia was an independent predictor of death in women only, while thrombocytopenia and elevated plasma glucose concentration were predictors of death in men only. Conclusions In patients with diabetes admitted for COVID-19, female sex was associated with lower incidence of early severe outcomes, but did not influence the overall in-hospital mortality, suggesting that diabetes mitigates the female protection from COVID-19 severity. Sex-associated biological determinants may be useful to optimize COVID-19 prevention and management in women and men.

International audience; The SPALAX-NG is a new-generation system that is designed to detect radioactive xenon at trace levels in the atmosphere following a nuclear explosion or civilian source release. This new system formed part of a validation program led by the Provisional Technical Secretary of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) Organization. In this study, the first SPALAX-NG unit was tested for six months between October 2018 and April 2019 at the CEA/DIF premises near Paris, France. This test period provided an outstanding opportunity to illustrate the high level of detectability and reliability of the system. The data availability obtained over this period was approximately 99%, which was well above the CTBT Data Availability criteria of 95%. The data reliability was demonstrated by a comparison with a collocated SPALAX-1 unit (former version of SPALAX) and by re-measuring several samples at the CTBT-certified French laboratory FRL08. The high sensitivity to the detection of the four relevant radioxenon isotopes was fully demonstrated and enabled the recording of a major dataset for western Europe. A large set of isotopic ratios was measured, which enabled the discrimination criteria between civilian sources and nuclear test signatures to be refined.

Introduction Il n’est pas demontre qu’un seuil d’HbA1c serait utile pour predire la survenue de complications materno-foetales en cas de DG, ni si ce seuil pourrait etre different en cas de DG precoce versus DG tardif. Materiels et methodes Etude observationnelle chez 4384 patientes DG avec facteurs de risque entre 2011 et 2018. L’HbA1c etait divisee en 5 classes. L’association entre l’HbA1c et les complications a ete evaluee apres ajustement sur les facteurs de risque de DG, en comparaison au groupe avec HbA1c la plus basse. Resultats L’HbA1c a ete dosee a 25 ± 7,5 SA pour une valeur de 5,2 % ± 0,4. 41,6 % ont presente au moins une complication parmi LGA, SGA, la pre-eclampsie, la prematurite, le transfert en neonatologie et la dystocie des epaules (critere composite). L’HbA1c ≥ 5,6 % est associee a une augmentation du risque de LGA (OR pour 5,6-5,9 = 2,12 (IC 95 % = 1,29-3,46) et OR > 5,9 =2,06 (IC 95 % = 1,14-3,7)) et de cesarienne (OR pour 5,6-5,9 = 1,64 (IC 95 % = 1,06-2,53) ; OR pour > 5,9 = 1,58 (IC 95 % = 0,93-2,7)). La prematurite augmente en cas d’HbA1c > 5,9 % (OR = 3,33 (IC 95 % = 1,27-8,71)). Apres ajustement, nous confirmons ces resultats pour LGA, prematurite, et cesarienne. L’association entre l’HbA1c et le critere composite reste significative. Les resultats sont similaires en cas de DG precoce ou tardif. Conclusion L’HbA1c est utile pour identifier des patientes les plus a risque de complications. Il n’apporte pas d’interet supplementaire que le DG soit precoce ou tardif.

Summary The standard of care trimodality therapy for resectable locally advanced esophageal adenocarcinoma is complex and necessitates multidisciplinary care and expertise. In this work, it is hypothesized that facility clinical volume and utilization of intensity-modulated radiotherapy (IMRT) may influence outcomes. The National Cancer Data Base was queried for patients with cT1-4-N0-3 M0 esophageal adenocarcinoma undergoing trimodality therapy from 2004 to 2013 (n = 2445). All patients received chemoradiation followed by esophagectomy at a Commission on Cancer facility. The facility volume was categorized into tertiles: high-volume centers (HVCs) in the highest 25th percentile of cases per year, intermediate-volume centers (IVCs) with the next highest 25th percentile of cases, and low- and very low-volume centers (LVCs) in the lowest 50th percentile. Overall survival (OS) was estimated using Kaplan–Meier methods and Cox proportional hazard regression. Propensity score matching to balance patient characteristics between volume centers was performed. Subgroup analysis was done comparing IMRT versus 3D conformal radiotherapy. The median follow-up was 26 months. Treatment at an HVC (hazard ratio 0.63, 95% CI 0.49–0.81, P

To assess the diagnostic performance of a new device for in situ label-free fluorescence spectral analysis of breast masses in freshly removed surgical specimens, in preparation for its clinical development. Sixty-four breast masses from consenting patients who had undergone either a lumpectomy or a mastectomy were included. Label-free fluorescence spectral acquisitions were obtained with a 25G fibre-containing needle inserted into the mass. Data from benign and malignant masses were compared to establish the most discriminating thresholds and measurement algorithms. Accuracy was verified using the bootstrap method. The final histological examination revealed 44 invasive carcinomas and 20 benign lesions. The maximum intensity of fluorescence signal was discriminant between benign and malignant masses (p < .0001) whatever their sizes. Statistical analysis indicated that choosing five random measurements per mass was the best compromise to obtain high sensitivity and high negative predictive value with the fewest measurements. Thus, malignant tumours were identified with a mean sensitivity, specificity, negative and positive predictive value of 98.8%, 85.4%, 97.2% and 93.5%, respectively. This new in situ tissue autofluorescence evaluation device allows accurate discrimination between benign and malignant breast masses and deserves clinical development. • A new device allows in situ label-free fluorescence analysis of ex vivo breast masses • Maximum fluorescence intensity discriminates benign from malignant masses (p < .0001) • Five random measurements allow a high negative predictive value (97.2%)

Aim DIALOG assessed the prevalence and predictors of hypoglycaemia in patients with type 1 (T1DM) or insulin-treated type 2 diabetes mellitus (T2DM) in a real-life setting. Methods In this observational study, insulin-treated patients ( n =3048) completed prospective daily questionnaires reporting the frequency and consequences of severe/confirmed non-severe hypoglycaemia over 30 days. Patients ( n =3743) also retrospectively reported severe hypoglycaemia over the preceding year. Results In this prospective survey, 85.3% and 43.6% of patients with T1DM and T2DM, respectively, reported experiencing at least one confirmed hypoglycaemic event over 30 days, while 13.4% and 6.4%, respectively, reported at least one severe event. Hypoglycaemia frequency increased with longer duration of diabetes and insulin therapy. Strongly predictive factors for hypoglycaemia were previous hypoglycaemia, >2 injections/day, BMI 2 and duration of insulin therapy>10 years. HbA 1c level was not predictive of hypoglycaemia in either T1DM or T2DM. The confirmed hypoglycaemia rate was increased in the lowest compared with the highest tertile of HbA 1c in T1DM, but not T2DM. At the time of enrolment, physicians reported severe hypoglycaemia in 23.6% and 11.9% of T1DM and T2DM patients, respectively, during the preceding year; the retrospective survey yielded frequencies of 31.5% and 21.7%, respectively. Also, severe hypoglycaemia led to medical complications in 10.7% and 7.8% of events in T1DM and T2DM patients, respectively, over 30 days. Conclusion Using a unique combined prospective and retrospective approach, the DIALOG study found a relatively high frequency of hypoglycaemia among insulin-treated patients. These findings emphasize the importance of a patient-centred approach for managing diabetes in which hypoglycaemia risk evaluation is critical. Trial registration ClinicalTrials.gov: NCT01628341.

Background: Self-management of diabetes minimizes the risk of macrovascular and microvascular complications, but understanding and/or adherence to self-management recommendations is often suboptimal. DIABEO is a smartphone app (downloaded via the internet) used to calculate bolus insulin doses. A previous study (TELEDIAB 1) showed that the use of DIABEO was associated with a significant improvement in glycemic control in patients with poorly controlled type 1 diabetes mellitus, particularly when combined with teleconsultations with physicians. Objective: Here, we present the protocol for a new study (Suivi A Grande Echelle d’une cohorte de diabetiques de type 1 et de type 2 sous schema insulinique basal bolus par la TELEmedecine; abbreviated TELESAGE), conducted in a larger population of diabetic patients with poorly controlled basal-bolus insulin levels. Methods: TELESAGE is a multicenter, double-randomized, open-label, three parallel–arms study, conducted in approximately 100 centers in France. The study will compare a control group (arm 1: usual follow-up) with two DIABEO telemedicine systems: (1) physician-assisted telemedicine (arm 2), and (2) nurse-assisted telemonitoring and teleconsultations by a diabetologist’s task delegation (arm 3). Initial randomization will allocate the study arms in 12 French regions. A second randomization will assign patients in the groups allocated to each studied region. The primary objective of TELESAGE will be to investigate the effect of the DIABEO telemedicine system versus usual follow-up, with respect to improvements in the glycated hemoglobin levels of approximately 696 diabetic patients with poorly controlled basal-bolus insulin levels. Results: The TELESAGE study is sponsored by Sanofi (Gentilly, France). A primary completion date is expected in June 2018, and publication of results is expected within 6 months of work completion. Conclusions: The TELESAGE study is expected to confirm the previous results of the TELEDIAB 1 study using a larger sample of diabetic patients. It is also expected to evaluate a nurse-assisted telemonitoring system. We will assess the potential of the DIABEO telemedicine service in terms of its utility and explore whether it can become an integral part of diabetes care for patients. Trial Registration: ClinicalTrials.gov NCT02287532; https://clinicaltrials.gov/ct2/show/NCT02287532 (Archived by WebCite at http://www.webcitation.org/6ykajhJKd)

Morbid obesity increases the risk of cardiovascular disease (CVD). The receptor for advanced glycation end-products (RAGE) is implicated in proinflammatory processes that underlie CVD. Its soluble form (sRAGE) has been proposed as a vascular biomarker. Recently, anti-sRAGE autoantibodies were described and found to be increased in diseases where RAGE is overexpressed. This study aimed to investigate serum levels of anti-sRAGE autoantibodies in morbidly obese patients.After exclusion based on specific criteria, 150 subjects (50 normoglycemics, 50 glucose-intolerants and 50 diabetics) were randomly recruited from a cohort of 750 obese patients (ABOS). Serum sRAGE and anti-sRAGE autoantibodies were measured before bariatric surgery. Sixty-nine patients were followed for up to 1year after gastric bypass, and their levels of sRAGE and anti-sRAGE autoantibodies measured. The control group consisted of healthy blood donors.Compared with controls, baseline levels of sRAGE and anti-sRAGE autoantibodies were significantly higher in all obese patients independently of glucose regulation (P0.001). At 1year after gastric bypass, sRAGE and anti-sRAGE were decreased (P0.001). The decrease in anti-sRAGE autoantibodies was correlated with an increase in high-density lipoprotein (HDL; P=0.02).Independently of previous diabetic status, morbid obesity increases sRAGE and anti-sRAGE levels. Weight loss after gastric bypass is followed by a decrease in both titres. The decrease in anti-sRAGE correlates with an increase in HDL.

We compared pathologic complete response (pCR) rate, toxicity, and postoperative complications between patients treated preoperatively with 50.4 Gy versus dose escalation with dose-painting intensity-modulated radiation therapy (dp-IMRT) to 56 Gy in locally advanced esophageal cancer. We evaluated esophageal cancer patients treated between 2006 and 2014 with preoperative IMRT chemoradiation to a dose of 50.4 Gy versus 56 Gy. The endpoints were pCR and toxicity. We identified 113 patients (50.4 Gy: n = 40; 56 Gy: n = 73). There were no significant differences in tumor or patient characteristics. Patients treated with 56 Gy demonstrated a higher pCR rate (56.2% vs. 30.0%) and lower pathologic nonresponse rate (4.1% vs. 20.0%) compared to patients treated to 50.4 Gy (P = 0.008). This remained significant on multivariate analysis (OR 3.375 95%CI 1.3-8.8, P = 0.013). Patients treated to 56 Gy also had an improved 3-year locoregional control rate compared to those treated to 50.4 Gy (93.8% vs. 78.5%; P = 0.022). The estimated 3-year freedom from failure was also superior in the 56 Gy arm (73.7% vs. 52.2%; P = 0.051), approaching significance. There were no differences in treatment related grade ≥3 toxicities, hospital admissions, feeding tube, esophageal stent placement, or dilation. There was, however, a statistically significant increase in postoperative atrial fibrillation in patients treated with 56 Gy (30.1% vs. 12.5%; P = 0.036). There was no difference in postoperative 30 or 60 day mortality. Dose escalation to 56 Gy with dp-IMRT is safe and results in significantly higher complete pathologic response rates in esophageal cancer without an increase in treatment-related toxicity. Prospective trials using dp-IMRT are needed to address the role of dose escalation on pCR rate and survival in esophageal cancer.

Background and aimsMultidrug resistance (MDR) limits effectiveness in treating malignancy by modifying internalisation and/or externalisation of drugs through cancer cell membranes. In this study we describe an assay to monitor patients’ responses to chemotherapy.MethodsThe assay is based on the fluorescent properties of doxorubicin alone as well as in combination with methotrexate, vinblastine, doxorubicin and cisplatin (MVAC). The slide-based cell imaging technique was first optimised using a panel of breast and urothelial cancer cell lines and then extended to fine needle breast aspiration biopsy and urine cytology.ResultsThe drug fluorescence behaviour observed on smears of clinical specimens is identical to that obtained using fixed cultured cells. The fluorescence of sensitive cells to chemotherapy is mainly localised in the nucleus, whereas resistant cells show a weak fluorescence signal localised in the cytoplasm. The difference in terms of fluorescence intensity is also highlighted through fluorescence spectra. ConclusionsThe results suggest that the assay provides clinically valuable information in predicting responses to doxorubicin and/or MVAC therapy. Originally set up on a confocal microscope, the assay was also effective using a standard epifluorescence microscope; as such it is technically simple, reliable and inexpensive.

International audience; The phenomenon of heat and mass transfer by condensation of water vapour from humid air involves several key concepts in aerobic bioreactors. The high performance of bioreactors results from optimised interactions between biological processes and multiphase heat and mass transfer. Indeed in various processes such as submerged fermenters and solid-state fermenters, gas/liquid transfer need to be well controlled, as it is involved at the microorganism interface and for the control of the global process. For the theoretical prediction of such phenomena, mathematical models require heat and mass transfer coefficients. To date, very few data have been validated concerning mass transfer coefficients from humid air inflows relevant to those bioprocesses. Our study focussed on the condensation process of water vapour and developed an experimental set-up and protocol to study the velocity profiles and the mass flux on a small size horizontal flat plate in controlled environmental conditions. A closed circuit wind tunnel facility was used to control the temperature, hygrometry and hydrodynamics of the flow. The temperature of the active surface was controlled and kept isothermal below the dew point to induce condensation, by the use of thermoelectricity. The experiments were performed at ambient temperature for a relative humidity between 35-65% and for a velocity of 1.0 ms(-1). The obtained data are analysed and compared to available theoretical calculations on condensation mass flux.

Introduction Le diabete est associe a des modifications cognitives aggravees par les complications vasculaires, un desequilibre glycemique, des hypoglycemies. L’objectif principal de cette etude etait de determiner la frequence des troubles cognitifs dans une cohorte de patients diabetiques âges de 50 ans et plus. L’objectif secondaire etait d’evaluer les facteurs associes a ces troubles. Patients et methodes Etude prospective sur 5 mois dans le service d’endocrinologie au CHRU de Lille. Evaluation cognitive par la MOCA realisee par un neuropsychologue. Score ≤ 25 en faveur d’un deficit cognitif. Comparaison des deux groupes MOCA normal versus pathologique en tenant compte des variables : âge, sexe, duree d’evolution du diabete, traitements, HbA1 C, complications vasculaires, HTA, tabagisme, alcoolisme, dyslipidemie, IMC, depression, sedentarite, plainte cognitive. Resultats Cent quatre-vingt-onze patients evalues (25 DT1 et 166 DT2), 67 avaient un score au MOCA ≤ 25. La frequence des troubles cognitifs etait de 35 %. Les patients avec un deficit cognitif etaient plus âges (p = 0,0377 ; âge moyen : 65,2 ± 8,5 ans vs 62,7 ± 7,8 ans), presentaient plus de complications microangiopathiques (p = 0,04 ; moyenne : 1,02 vs 0,68) de retinopathie (p = 0,02 ; 39,39 % vs 23,77 %), de neuropathie (p = 0,03 ; 31,34 % vs 17,89 %), prenaient plus de traitement anti-hypertenseur (p = 0,04 ; 1,61 vs 1,32), etaient plus sous anti-coagulant (p = 0,02 ; 14,93 % vs 4,84 %), etaient plus sedentaires (p = 0,001 ; 62,12 % vs 36,67 %). Pas de difference significative concernant les autres variables. Discussion Plus d’un patient sur trois presentait des troubles cognitifs. Les facteurs associes etaient ceux classiquement rapportes dans la litterature. La frequence elevee suggere l’interet d’un depistage systematique afin de realiser un plan de soin personnalise.

La grossesse presente un risque d’apparition et d’aggravation d’une retinopathie diabetique (RD) dont la frequence et les facteurs predictifs varient selon les etudes. L’objectif de l’etude est d’evaluer la prevalence et les facteurs de risque d’apparition ou d’aggravation d’une RD pendant la grossesse chez des patientes diabetiques de type 1. L’etude inclut 499 grossesses chez 375 patientes diabetiques de type 1 suivies dans une structure multidisciplinaire au CHRU de Lille, ayant accouche entre 1997 et 2015. Les donnees diabetologiques, obstetricales et ophtalmologiques ont ete recueillies a partir des dossiers medicaux. Le suivi ophtalmologique consistait en la realisation trimestrielle d’un fond d’œil et/ou angiographie, mensuelle en cas de retinopathie initiale severe ou d’aggravation pendant la grossesse. Une progression de la RD a ete observee dans 21,8 % des grossesses (24,4 % d’apparition parmi les 348 grossesses sans retinopathie initiale et 15,9 % d’aggravation parmi les 151 grossesses avec retinopathie preexistante). On note une regression dans le post-partum pour 9,3 % des grossesses. L’anciennete du diabete ( p p p p p

Observation Nous rapportons deux observations de macro-adenomes somatotropes agressifs (grade 2b) evolutifs sous analogue de la somatostatine de premiere generation, pour lesquels le pasireotide LP a permis le controle de l’hypersomatotropisme et du volume tumoral. Cas 1 Macro-adenome invasif avec IGF-I a 734 ng/mL (N Cas 2 Macro-adenome geant somatotrope (IGF-I 422 ng/mL [n Discussion Ces deux observations illustrent l’interet d’un traitement par pasireotide LP dans les adenomes somatotropes agressifs partiellement resistants aux analogues de la somatostatine pour son efficacite anti-secretoire mais surtout anti-tumorale dans ce contexte particulier.

PREDICTIVE (an ongoing multinational observational study) provides an opportunity to explore the impact of insulin detemir use in routine clinical practice. Here, we report on long-term (52-week) data from a French cohort of patients (n=1772), comprising 643 with type 1 diabetes and 1129 with type 2 diabetes.Patients were prescribed insulin detemir at their physician's discretion and assessed at various visits (baseline, 12 weeks, 26 weeks and 52 weeks). The primary endpoint was the frequency of serious adverse drug reactions, including major hypoglycaemia. Secondary endpoints included minor and nocturnal hypoglycaemia, glycaemic control (HbA(1c), fasting blood glucose and variability of fasting blood glucose) and weight change.The incidence of serious adverse drug reactions was low throughout the study, seen in 10 patients with type 1 diabetes (14 events, 1.6%) and seven with type 2 diabetes (seven events, 0.6%). In both type 1 and type 2 diabetes cohorts, the overall minor and nocturnal hypoglycaemic events were reduced from baseline (P0.001), with no clinically significant changes in weight from baseline to endpoint. After 52 weeks of treatment with insulin detemir, glycaemic control improved, with reductions in: HbA(1c), by -0.6% and -0.8% in type 1 and type 2 diabetes patients, respectively; fasting blood glucose, by -1.4mmol/L and -1.9mmol/L respectively; and FBG variability, by -0.8mmol/L and -0.3mmol/L, respectively (P0.0001 for all).Patients treated with insulin detemir in a clinical healthcare setting improved their glycaemic control with no increases in hypoglycaemia, adverse events or weight compared with baseline.

The aim was to compare clinical outcomes by different dosing frequencies of insulin detemir (detemir) used over 52 weeks in various regimens. Methods: This analysis involved French patients enrolled in PREDICTIVE (a large-scale, multinational, observational study of empirical use of detemir in everyday clinical practice) for whom data have been collected over 52 weeks. Three cohorts were considered: patients with type 1 diabetes; patients with type 2 diabetes using detemir in a basal insulin plus oral antidiabetic drug (OAD) regimen; patients with type 2 diabetes using detemir as part of basal-bolus insulin therapy. In each cohort, data were stratified according to detemir dosing frequency at the beginning and end of 52 weeks: once daily (o.d.) at the beginning and end; twice daily (b.i.d.) at the beginning and end; o.d. at the beginning, but b.i.d. at the end. Endpoints assessed included glycated hemoglobin, fasting plasma glucose, hypoglycemia, weight, and insulin dose. There were improvements in glycemic control and tolerability in all subgroups. Patients completing on o.d. dosing tended to have better outcomes than those completing on b.i.d. dosing in all cohorts, and o.d. administration was associated with lower insulin dosing. There was little evidence that switching from o.d. to b.i.d. dosing influenced outcomes other than insulin dose. However, there were some baseline differences between subgroups selected for o.d. and b.i.d. dosing that might have influenced outcomes: many patients appeared to have been continued on previous basal dosing frequencies; for others, b.i.d. detemir dosing seemed to be used to intensify previous therapy. With the caveat that empirical choices of dose frequency were made, this analy-sis shows that empirical use of o.d. detemir produces results at least as good as empirical use of b.i.d. detemir in basal-bolus-treated type 1 and type 2 diabetes, and in basal plus OAD-treated type 2 diabetes.

Aims To estimate the prevalence of diagnosed type 2 diabetes mellitus in the French general population. Secondary objectives were to evaluate treatments and diabetic complications. Methods In this cross-sectional epidemiological survey, a representative sample of the French adult population was selected using a stratified quota method: 10,038 individuals were evaluated by a standardized face-to-face interview. The diagnosis of type 2 diabetes was determined on the basis of replies to six questions using a specific algorithm. Data were collected on risk factors, diabetes history, familial antecedents and diabetic complications. These patients also identified their treatments from an exhaustive list. Results The prevalence of type 2 diabetes was 5.08% in men and 4.11% in women, and rose progressively after the age of 50. Of these, 79patients (13.4%) received no pharmacological treatment, 477 (80.9%) were taking an oral antidiabetic drug and 134 (22.7%) were taking insulin. Renal and ocular complications were reported by 6.8% and 21.0%, respectively, of the patients. Also, 10.4% had been hospitalized at some time of that year for a diabetes-related problem. The most frequently reported treatments were metformin and sulphonylureas, used by more than 50% of the patients. In addition, 380 patients (65.9%) claimed to be following a diet and 228 (39.2%) were consulting a dietitian. Conclusion The prevalence of treated and untreated type 2 diabetes mellitus in France was 4.57%.

Resume A partir des donnees de la litterature, ce point de vue d'expert discute l'interet du depistage ainsi que la prise en charge du diabete gestationnel. Selon les populations etudiees, sa frequence varie de 1 a 14 %. Son traitement repose principalement sur le regime dietetique et l'insulinotherapie, dont l'etude ACHOIS a montre qu'elle diminuait significativement le risque de complications perinatales severes (de 4 a 1 %). La place des antidiabetiques oraux (glyburide) reste a definir. Dans la plupart des pays developpes, le depistage du diabete gestationnel repose sur la realisation de tests de charge en glucose : test de Sullivan (une heure) eventuellement suivi d'une hyperglycemie a 100 g (trois heures) ; hyperglycemie a 75 g (deux heures). Le depistage du diabete gestationnel est necessaire, car sa prise en charge diminue le risque de complications perinatales severes. Cependant, il n'existe pas de preuve qu'un depistage systematique soit plus efficace qu'un depistage cible sur des populations a risque, avec des criteres qui sont tres variables d'une etude a l'autre.

The aim of this work was to study an externally-submerged membrane bioreactor for the cyclic extraction of volatile fatty acids (VFAs) during anaerobic fermentation, combining the advantages of submerged and external technologies for enhancing biohydrogen (BioH2) production from agrowaste. Mixing and transmembrane pressure (TMP) across a hollow fiber membrane placed in a recirculation loop coupled to a stirred tank were investigated, so that the loop did not significantly modify the hydrodynamic properties in the tank. The fouling mechanism, due to cake layer formation, was reversible. A cleaning procedure based on gas scouring and backwashing with the substrate was defined. Low TMP, 10(4)Pa, was required to achieve a 3Lh(-1)m(-2) critical flux. During fermentation, BioH2 production was shown to restart after removing VFAs with the permeate, so as to enhance simultaneously BioH2 production and the recovery of VFAs as platform molecules.

The IDAHO 2 epidemiological survey was conducted in departments of diabetology in insulin-naïve type 2 diabetics for whom insulin was initiated. The objective was to assess the patients' profile, the treatments proposed during hospital stay and after one year.797 patients were analysed. Their characteristics were: age 64+/-12 years, 49% males, weight: 78+/-17 kg, BMI: 29+/-6 kg/m2, diabetes duration 11 years, prevalence of complications: 68%, fasting blood glucose 13+/-6 mmol/l, HbA1c: 10+/-2.2%; treatment prior to insulin comprised: at least 2 OHA: 71% of cases, one: 21%, no OAD: 8%. At hospital discharge, 54% of the patients used basal insulin. After 1 year, 670 continued on insulin. The insulin initiation was accompanied by a decrease in the FBG level (baseline: 13+/-6 mmol/l; final: 8.5+/-2.75 mmol/l; P0.0001) and a HbA1c improvement (baseline: 10+/-2.2%; final: 7.9+/-1.4%; P0.0001). This was observed du-ring the first 6 months (HbA1c: 7.8%, P0.0001 versus baseline). 80% of the patients remained on the same insulin regimen after 1 year: 35% had 1 injection/day, 44% had 2, 12% had 3 and 9% had a complex regimen. The weight gain, the final daily dose and hypoglycaemias increased with the number of injections. The mean daily insulin dose was 33 U/day (24 U with 1 injection/day).The IDAHO study shows that insulin is effective in type 2 diabetics however, management is inadequate with insulin therapy being initiated too late and at doses which are low after one year.

International audience; Fluorescence correlation spectroscopy (FCS) under two-photon excitation was used successfully to characterize the diffusion properties of model virus particles (bacteriophages) in bacterial biofilm of Stenotrophonas maltophilia. The results are compared to those obtained with fluorescent latex beads used as a reference. The FCS data clearly demonstrated the possibility for viral particles to penetrate inside the exopolymeric matrix of mucoid biofilms, and hence to benefit from its protective effect toward antimicrobials (antibiotics and biocides). Microbial biofilms should hence be considered as potential reservoirs of pathogenic viruses, and are probably responsible for numerous persistent viral infections.; La spectroscopie de corrélation de fluorescence (FCS) sous excitation à deux photons a été utilisée avec succès pour caractériser les propriétés de diffusion de particules virales modèles (bacteriophages) dans un biofilm bactérien de Stenotrophonas maltophilia. Les résultats ont été comparés avec ceux obtenus pour des billes de latex fluorescentes utilisées comme référence. Les données obtenues en FCS démontrent la possibilité pour une particule virale de pénétrer dans la matrice exopolymérique de biofilms mucoïdes, et de bénéficier ainsi d'un environnement protecteur vis-à-vis d'agressions extérieures telles que l'action d'agents antimicrobiens (antibiotiques ou désinfectant). Les biofilms peuvent ainsi être considérés comme des réservoirs potentiels de virus pathogènes, et sont probablement impliqués dans de nombreuses infections virales persistantes.

Summary Objective Self monitoring of blood glucose (SMBG) in type 2 diabetes is a topic of current interest (imbalance between increased health-care costs and improvement in compliance with treatment and diet). An open label randomized prospective study was designed to compare changes in metabolic control over 6 months in patients managed with usual recommendations alone (conventional assessment group) or combined with SMBG. Research design and methods Patients not treated with insulin or previously self monitored, 40 to 75 years of age, with a diagnosis of type 2 diabetes > 1 year and standardized HbA 1c level ≥ 7.5 and ≤ 11% were randomized to either a control group or SMBG group. They were followed up every 6 weeks over 24 weeks. Patients in the SMBG group were given the same device (Ascensia Esprit® Discmeter, Bayer) and were required to perform at least 6 capillary assays a week (3 different days of the week, including weekend). Management of patients was standardized, including drugs, diet and physical activity. The primary efficacy criterion was change in HbA 1c level in Intent To Treat (ITT) patients. Assays were performed at baseline, at 3 and 6 months using the calibrated DCA 2000® device (Bayer). Results Two hundred sixty five general practitioners randomized 988 patients (ITT Population), but 689 patients were evaluable for the primary criterion. At the endpoint, HbA 1c was lower in the SMBG group (8.1 ± 1.6%) than in the conventional treatment group (8.4 ± 1.4%, P = 0.012). The change in HbA 1c levels between baseline and endpoint was classified into two classes: improvement if a change > 0.5% occurred, stability or worsening in case of a change ≤ 0.5%; 57.1% of patients in the SMBG group vs 46.8% in the control group had an improvement in HbA 1c level ( P = 0.007) after 3 months. A steady state was reached during the last 3 months. A multivariate logistic regression analysis was performed and identified factors predictive of improvement in HbA 1c levels: HbA 1c at baseline: odd ratio (OR) = 1.749 ( P P = 0.015), duration of diabetes: OR=0.953 ( P = 0.001) and BMI: OR=0.962 ( P = 0.039). Conclusions This study is the first multicenter, controlled, prospective trial conducted on a large number of patients demonstrating that SMBG was statistically associated with a better quality of metabolic control than usual traditional recommendations alone in type 2 diabetes.

La grossesse presente un risque d’apparition et d’aggravation d’une retinopathie diabetique (RD) dont la frequence et les facteurs predictifs varient selon les etudes. L’objectif de l’etude est d’evaluer la prevalence et les facteurs de risque d’apparition ou d’aggravation d’une RD pendant la grossesse chez des patientes diabetiques de type 1. L’etude inclut 499 grossesses chez 375 patientes diabetiques de type 1 suivies dans une structure multidisciplinaire au CHRU de Lille, ayant accouche entre 1997 et 2015. Les donnees diabetologiques, obstetricales et ophtalmologiques ont ete recueillies a partir des dossiers medicaux. Le suivi ophtalmologique consistait en la realisation trimestrielle d’un fond d’œil et/ou angiographie, mensuelle en cas de retinopathie initiale severe ou d’aggravation pendant la grossesse. Une progression de la RD a ete observee dans 21,8 % des grossesses (24,4 % d’apparition parmi les 348 grossesses sans retinopathie initiale et 15,9 % d’aggravation parmi les 151 grossesses avec retinopathie preexistante). On note une regression dans le post-partum pour 9,3 % des grossesses. L’anciennete du diabete ( p p p p p

Adoptive transfer of T cells reactive to minor histocompatibility antigens has the unmatched ability to eradicate malignant hematopoietic cells. Unfortunately, its use is hampered by the associated graft-versus-host disease. The critical issue of a possible dissociation of the antileukemic effect and graft-versus-host disease by targeting specific minor histocompatibility antigens remains unresolved because of the unknown nature and number of minor histocompatibility antigens necessary or sufficient to elicit anti-leukemic activity and graft-versus-host disease. We found that injection of T lymphocytes primed against a single major histocompatibility complex class I-restricted immunodominant minor histocompatibility antigen (B6dom1) caused no graft-versus-host disease but produced a curative anti-leukemic response. Avoidance of graft-versus-host disease required that no other host-reactive T cells be co-injected with T cells primed with B6dom1. Here we show that effective and non-toxic immunotherapy of hematologic malignancies can be achieved by targeting a single immunodominant minor histocompatibility antigen.

The intercalating antitumoral drug pazelliptine (PZE) is able to photosensitize the formation of single- and double-strand breaks in supercoiled plasmid DNA and selective photocleavage at guanine residues is observed. In order to understand the mechanisms of DNA cleavage mediated by the photoexcited drug, singlet and triplet excited-state processes in PZE complexed with poly(dA-dT)-poly(dA-dT), poly(dG-dC)-poly(dG-dC) and calf thymus DNA have been investigated by means of single photon counting fluorescence decay and transient absorption techniques. For each complex, three different binding sites have been identified, due to the existence of different geometric structures of the drug in the ground state. For one type of binding site, a proton transfer reaction occurs in the singlet excited state whatever the nucleic acid environment. In contrast, the relaxation dynamics for the other two sites are found to depend widely upon the type of polynucleotide in which the drug has been intercalated. From the results of this study, we suggest that the photodynamic action of PZE does not originate from excitation of the drug in the environment of G-C base pairs but is initiated from its triplet state that reacts by electron transfer with the adenine bases. The specificity of cleavage could be the result of subsequent reactions leading to guanine oxidation.

Introduction Malgre l’amelioration des pratiques, la grossesse reste associee a une morbidite materno-fœtale elevee chez la DT1. Notre objectif a ete d’evaluer l’equilibre metabolique et le devenir materno-fœtal chez des DT1 traitees par pompe a insuline Patients et methodes Nous avons etudie retrospectivement 241 grossesses DT1 issues des CHRU de Lille et Toulouse entre 2006 et 2012, toutes prises en charge dans le cadre d’une structure multidisciplinaire selon le referentiel de la SFD. Nous avons compare deux groupes : G1 (n = 180) traite par pompe avant la conception et G0 (n = 61) initiant ce traitement en cours de grossesse. Resultats Les patientes de G1 etaient plus âgees (30,4 ± 5,0 vs 28,4 ± 5,3 ans, p Conclusion L’utilisation de l’insulinotherapie par pompe avant la grossesse permet une amelioration de l’equilibre metabolique sans augmenter le risque d’acidocetose. Cependant, compte-tenu du faible nombre d’evenements, notre etude n’a pas mis en evidence de reduction significative de la morbidite materno-fœtale. Declaration d’interet Les auteurs declarent ne pas avoir d’interet direct ou indirect (financier ou en nature) avec un organisme prive, industriel ou commercial en relation avec le sujet presente.

Introduction Grâce a des methodes pharmacologiques induisant une hypercapnie, une alteration de la vasoreactivite cerebrale alteree a ete mise en evidence chez des patients diabetiques de type 1 (DT1) mal equilibres et indemnes de complications microvasculaires. Notre hypothese est que la vasoreactivite cerebrale pourrait etre egalement compromise en reponse a des situations physiologiques stimulatrices de la perfusion regionale cerebrale, tel que l'exercice exhaustif. Materiels et methodes Des adultes DT1, indemnes de complications, divises en deux groupes (HbA1c n =8 et HbA1c > 8 %, n =10), apparies a des temoins sains, ont realise un exercice progressif exhaustif avec mesure des variations d'oxyhemoglobine, de desoxyhemoglobine et d'hemoglobine totale, au niveau du cortex prefrontal gauche, par spectroscopie du proche infrarouge. Des prelevements veineux et capillaires arterialises au repos et a l'exercice maximal ont ete realises afin de mesurer les variables qui sont connues par leurs actions sur l'hemodynamique cerebrale et qui peuvent etre modifiees par le diabete et/ou l'exercice physique (PaCO2, pH et insuline libre). Resultats L'augmentation de l'hemoglobine totale (effets groupe p p p Conclusion L'exercice physique maximal permet de mettre en exergue des alterations fonctionnelles de la microcirculation, au niveau du cortex prefrontal, avant meme l'apparition de complications microvasculaires detectables par les tests cliniques habituels. Ces alterations fonctionnelles sont probablement la consequence de l'effet deletere de l'hyperglycemie chronique sur la fonction endotheliale. Declaration d’interet Les auteurs declarent ne pas avoir d'interet direct ou indirect (financier ou en nature) avec un organisme prive, industriel ou commercial en relation avec le sujet presente.

Numerous minor histocompatibility antigens (MiHAs) show tissue-specific expression and can induce vigorous T cell responses. They therefore represent attractive targets for leukemia immunotherapy mediated by adoptive transfer of T cells. The main objective of this work was to determine whether MiHAs expressed by normal hematopoietic cells were present on leukemic cells and whether they could trigger lysis by cytotoxic T lymphocytes (CTLs). CTL assays showed that mouse leukemic cells of both lymphoid and myeloid lineages were sensitive to CTLs targeted toward some but not all MiHAs. In four out of four strain combinations in which we primed CTLs against immunodominant MiHAs, effectors killed leukemic blasts, whereas no cytotoxicity was observed when CTLs were targeted toward four immunorecessive MiHAs. Testing of HPLC fractions obtained from normal and leukemic cells provided molecular evidence that leukemic blasts expressed only some of the MiHAs found on normal mouse hematopoietic cells. Decreased density of H-2 class I molecules at the surface of leukemic cells suggests that down-regulation of genes encoding either class I molecules or proteins involved in antigen processing played a role in the aberrant expression of MiHAs. In vivo resistance to the leukemic cells by various strains of mice correlated with in vitro CTL activity. These results show that leukemic cells express only some (immunodominant) MiHAs and suggest that this subset of MiHAs represent prime targets for adoptive immunotherapy.

Introduction L'objectif de cette analyse etait de determiner les caracteristiques des traitements injectables des diabetiques de type 2 en lien avec la repartition regionale des specialistes (diabetologues/endocrinologues). Au niveau national, le ratio medecin/patients DT2 est de un specialiste pour 1760 patients (entre 1 557 et 3 404 selon les regions) et de un medecin generaliste (MG) pour 52 patients (entre 34 et 80). Materiels et Methodes Suivi longitudinal et observationnel mene au sein de 21 regions administratives metropolitaines. Les donnees relatives aux traitements injectables (proportions, medecin initiateur…) ont ete analysees sur 12 mois (12/2013 – 11/2014), via les donnees des delivrances, avec chainage par patient, de 7 053 pharmacies extraites de la base LTD (Lifelink Treatments Dynamics) d'IMS Health. Resultats Parmi les 787 689 patients DT2 traites, 26 % etaient traites par injectables (± antidiabetiques oraux : ADOs) ; dont 4 % par agonistes du recepteur du GLP-1 et 16 % par insuline basale. Les traitements injectables ont ete majoritairement inities par un specialiste : 52 % (entre 34 et 64 %) et 59 % (entre 36 et 69 %) des patients traites respectivement par insuline basale ou agonistes du recepteur du GLP-1. Cependant, dans les regions ou la densite de specialistes est faible, les MGs ont effectue jusqu'a 2/3 des initiations d'injectables. Neanmoins, les specialistes restent les principaux initiateurs des traitements injectables. Sur 12 mois, ils ont initie en moyenne par medecin 28 (entre 14 et 87) et 7,5 (entre 4 et 26) traitements, respectivement par insuline basale ou agonistes du recepteur du GLP-1. Enfin, 44 % et 50 % des patients traites respectivement par insuline basale seule (± ADO), ou agonistes du recepteur du GLP-1 (± ADO), etaient suivis par un specialiste (seul ou avec un MG). L'intervention des specialistes croit avec la com-plexite du schema therapeutique : 61 % des patients sous insuline basale + rapides et 66 % pour le schema GLP-1 + insuline vus dans l'annee. Conclusions Ces donnees montrent que le specialiste est le principal initiateur des traitements injectables des DT2, meme dans la plupart des regions ou la densite de specialistes par patients DT2 traites est faible.

Introduction La grossesse chez la patiente DT1 reste une grossesse a risque. Obtenir une normoglycemie de la periode periconceptionnelle a la fin de grossesse est actuellement le seul facteur pronostique identifie afin de reduire la morbidite materno-fœtale meme s'il existe vraisemblablement d'autres facteurs impliques. L'objectif est de comparer le pronostic materno-fœtal et le controle metabolique chez des patientes DT1, traitees par pompe ambulatoire comparativement aux patientes traitees par multi-injections. Patients et Methodes Il s'agit d'une etude monocentrique a partir d'une base de donnees de patientes ayant accouche a Lille entre 2005 et 2013. Les patientes ont ete prises en charge par la meme equipe diabeto-obstetricale selon les recommandations actuelles Nous avons compare les complications maternofœtales, les issues de grossesse et l'evolution du controle metabolique chez 152 patientes traitees par pompe ambulatoire versus 103 patientes traitees par multi-injections. Parmi les patientes sous pompe, 121 patientes etaient sous pompe avant la grossesse et 31 patientes ont ete mises sous pompe pendant la grossesse. Resultats Les groupes etaient comparables en ce qui concerne l'âge, l'IMC, les antecedents d'HTA. Les patientes sous pompe avaient un diabete plus ancien ( p p p = 0,05) ainsi qu'une HbA 1c preconceptionnelle significativement plus basse ( p = 0,02) que les patientes sous multi-injections. L'equilibre metabolique s'est ameliore de facon identique dans les 2 groupes. Il n'y a pas de difference entre les 2 groupes en ce qui concerne l'aggravation de la retinopathie ou de la nephropathie. Il n'existe pas de difference en ce qui concerne le taux de preeclampsie, de prematurite, l'âge gestationnel a l'accouchement ni le taux de cesarienne. Le taux de macrosomie est plus eleve dans le groupe pompe ( p p Conclusions Cette etude confirme que meme s'il n'a pas ete demontre a ce jour une superiorite du traitement par pompe ambulatoire comparativement aux multi-injections, il est propose a une population avec plus de complications et a permis une reduction significative du taux de malformations congenitales.

Objectif Evaluer les moteurs et obstacles potentiels d’une gestion active et efficace du diabete parmi les professionnels de sante (PS). Materiels et methodes DAWN 2 est une enquete internationale (17 pays) soutenue par Novo Nordisk. En France, 288 PS ont participe a cette etude : 120 medecins generalistes (MG), 80 specialistes (Sp), 48 infirmiers (eres) et 40þdieteticien (ne) s (ID). Resultats 61 % ID vs 50 % Sp et 30 % MG estimaient que la reussite de la prise en charge des patients diabetiques dependait de leur capacite a apprehender et prendre en charge les problemes emotionnels de leurs patients. 68 % ID vs 48 % Sp et 32 % MG demandent la plupart du temps ou toujours a leurs patients comment le diabete affecte leur vie. 57 % ID vs 35 % Sp et 21 % MG pensent que les PS devraient collaborer davantage avec les associations de patients et de benevoles pour ameliorer les resultats a long terme de leurs patients. 80 % ID vs 46 % Sp et 29 % MG considerent que les PS dedies au diabete devraient recevoir une formation pour communiquer et soutenir les changements de comportement. 68 % ID vs 50 % Sp et 26 % MG desireraient ameliorer l’acces aux psychologues ou psychiatres. Discussion Le degre d’implication personnelle envers les patients, la posture et l’attention portee concernant l’aspect emotionnel du diabete et de son traitement, different en fonction du type de PS : les plus impliques sont les ID suivi des Sp puis des MG. L’intervention de specialistes de la sante mentale, formes a la problematique des maladies chroniques, comme celle deja mise en place pour les patients diabetiques souffrant de depression, pourrait etre benefique au sein des programmes de coordination des soins du diabete.

Objectif Evaluer l’etat emotionnel des personnes atteintes de diabete (PAD) et des membres de leurs familles (MF). Materiels et methodes DAWN2 est une enquete internationale soutenue par Novo Nordisk conduite dans 17 pays. En France, les entretiens ont concerne 120 MF [MF de diabetiques insulino-traites (MIT) et MF de diabetiques non insulino-traites (MNIT) et 500 PAD [80 avec un diabete de type 1 (DT1) ; 150 avec un diabete de type 2 (DT2) insulino-traite (DT2 Insuline) ; 170 DT2 non insulino-traites (DT2 Non-Insuline), 100 DT2 sans traitement antidiabetique (DT2 Non TT)] Ces deux populations ont complete deux questionnaires : le PAID « Problemes lies au diabete » – dont la version MF, nouvellement developpee pour DAWN2 – et le WHO-5 Well-Being Index. Resultats Parmi les domaines problematiques evalues par les MF (PAID), l’inquietude de l’avenir et du risque de complications, ainsi que l’anxiete de ne pas aider suffisamment la personne avec laquelle elles vivent, etaient considerees comme des problemes graves ou tres graves respectivement par 53 % et 26 % des MIT. Par ailleurs, 17 % des MIT semblaient etre depressifs (WHO-5). Concernant les PAD, environ la moitie des DT1, DT2 Insuline et DT2 Non TT, et 1/3 DT2 Non-Insuline ressentaient une grande detresse liee au diabete (PAID). 19 % DT1 et 15 % DT2 Insuline se sentaient accables par leur diabete. 14 % DT1 et 13 % DT2 Insuline semblaient etre depressifs (WHO-5). Conclusion L’anxiete et la detresse des personnes atteintes de diabete sont egalement eprouvees par les MF. Aussi, il apparait necessaire de soutenir aussi bien les personnes atteintes de diabete que leur entourage familial.

Introduction Le role du placenta dans les anomalies de croissance au cours du diabete maternel est tres important. Nous avons deja montre dans le placenta de rates gestantes diabetiques la surexpression du gene decidual-prolactin-related- protein (DPRP) et une elevation des produits antiangiogeniques issus du clivage de la prolactine, associees a une surexpression du gene de l’enzyme de clivage Bone-Morphogenetic-protein-1 (BMP-1). Les objectifs sont l’analyse cinetique de l’expression genique de la DPRP, de la BMP-1 et de la quantification des produits de clivage de la prolactine a differentes periodes de la gestation de rates diabetiques. Materiels et methodes Analyses placentaires effectuees a J14, J17 et J21 chez des rates gestantes Wistar rendues diabetiques au 7e jour recevant 65 mg/kg de streptozotocine (STZ) seule (n = 21) soit en association avec 75 mg/kg de Nicotinamide (NCT-STZ) (n = 23) comparativement a un groupe controle (n = 23). Nous avons recueilli les poids des ratons ainsi que les poids placentaires et avons analyse les expressions geniques placentaires de DPRP et BMP-1 par qRT-PCR et l’etude du clivage de la prolactine en western blot. Resultats Il existe un RCIU dans les ratons issus de rates diabetiques (p Conclusion Les derives de la famille de la prolactine sont deregules au 17e jour de gestation dans le placenta de femelles diabetiques. Ils pourraient jouer un role d’adaptation a une situation de stress qu’est l’hyperglycemie.

Urinary cytology is a noninvasive and unconstraining technique for urothelial cancer diagnosis but lacks sensitivity for detecting low-grade lesions. In this study, the fluorescence properties of classical Papanicolaou-stained urothelial cytological slides from patients or from cell lines were monitored to investigate metabolic changes in normal and tumoral cells. Time- and spectrally-resolved fluorescence imaging was performed at the single cell level to assess the spectral and temporal properties as well as the spatial distribution of the fluorescence emitted by urothelial cells. The results reveal quite different fluorescence distributions between tumoral urothelial cells, characterized by a perimembrane fluorescence localization, and the normal cells which exhibit an intracellular fluorescence. This is not caused by differences in the fluorescence emission of the endogenous fluorophores NAD(P)H, flavoproteins or porphyrins but by various localization of the EA 50 Papanicolaou stain as revealed by both the spectral and time-resolved parameters. The present results demonstrate that the use of single-cell endofluorescence emission of Papanicolaou-stained urothelial cytological slides can allow an early ex vivo diagnosis of low-grade bladder cancers.

Introduction La prevalence du DG a considerablement augmente avec une prise en charge soit en debut de grossesse soit au 2e trimestre. L’objectif a ete de determiner les caracteristiques maternelles et les issues de grossesse associees a un diagnostic precoce. Materiels et methodes Etude chez les DG avec facteurs de risque au CHRU de Lille entre fevrier 2011 et juillet 2013. Le diagnostic et la prise en charge ont ete effectues selon les recommandations. Quatre groupes ont ete determines en fonction du terme de diagnostic soit 1077 DG : 28 SA. Resultats 28,3 % diagnostiquees avant 15 SA, 10,7 % entre 15 et 23, 45,5 % entre 24 et 28 et 15,5 % apres 28 SA. Le depistage est realise avant 15 SA par une glycemie dans 99 % des cas, entre 15 et 23 SA par une glycemie dans 64,6 % des cas et une HGPO dans 35,4 %. Les patientes diagnostiquees precocement ont un IMC plus eleve (p Conclusion Les DG diagnostiquees precocement sont les plus a risque. Leur taux de macrosomie pourrait etre reduit par une prise en charge specifique ainsi que par la necessite d’une reduction ponderale en preconceptionnel. La prise en charge permet de reduire la macrosomie chez les DG diagnostiquees entre 24 et 28 SA. Declaration d’interet Les auteurs declarent ne pas avoir d’interet direct ou indirect (financier ou en nature) avec un organisme prive, industriel ou commercial en relation avec le sujet presente.

Introduction Depuis la loi HPST, les pharmaciens d'officine sont impliques dans l'accompagnement de patients atteints de maladie chronique. Le projet Diabetopharma visait a accompagner des pharmaciens d'officine dans la realisation d'entretiens individuels avec des patients diabetiques. Les impacts des entretiens sur les habitudes de vie des patients et le ressenti des pharmaciens et des medecins traitants ont ete evalues. Patients et methodes Des focus groups patients, pharmaciens et medecins generalistes ont ete realises pour determiner les attentes. Douze pharmaciens du Nord-Pas-de-Calais ont ete accompagnes, par un infirmier et un dieteticien specialises en education therapeutique, pour la realisation d'entretiens individuels d'environ 30 minutes au sein de leurs officines. L'ecoute empathique et la posture educative ont guide les entretiens de 70 patients. Les pharmaciens disposaient d'outils pedagogiques adaptes et ont ete encourages a informer les medecins traitants de la demarche et a leur transmettre un compte-rendu. Diabetopharma a ete evalue au travers de questionnaires de satisfaction et d'echanges avec les pharmaciens, les patients et leurs medecins generalistes. Resultats Les pharmaciens rapportent que le programme leur a permis d'etre sensibilises et inities a la posture educative a adopter lors d'entretiens individuels et a renforce leurs connaissances sur le diabete. 70 % des patients interroges a 3 mois de l'entretien observent un impact positif sur leurs habitudes de vie (vigilance alimentaire, augmentation de l'activite physique) mais un test appreciant l'observance therapeutique n'a pas ete ameliore. 80 % des medecins generalistes interroges apprecient l'initiative, instaurant un nouveau maillon dans le suivi des patients diabetiques. Ils encouragent le deploiement du projet a plus grande echelle. Conclusion Le pharmacien est un acteur du parcours de soins du patient diabetique. Cette etude demontre qu'un accompagnement par des professionnels experts en education ainsi que des outils specifiques apportent aux pharmaciens les moyens d'acquerir les competences necessaires a la realisation d'entretiens individuels. Un impact sur l'observance therapeutique necessitera une action dans la duree. Declaration d’interet Les auteurs declarent avoir un interet avec un organisme prive, industriel ou commercial en relation avec le sujet presente. Etude sponsorisee par Sanofi France.

Introduction Le diabete de type 2 (DT2) est une maladie familiale, avec transmission d'une susceptibilite genetique et de facteurs environnementaux. Environ 70 marqueurs genetiques du DT2 ont ete identifies. S'ils n'expliquent que 10 % de l'heritabilite, ils pourraient neanmoins jouer un role dans le developpement de la maladie sur plusieurs generations. Patients et methode L'objectif est de determiner l'heritabilite familiale (environnementale et genetique) du DT2 en recrutant des familles sur au moins deux generations, chacune des generations (G1 parents, G2 enfants) comprenant au moins un membre DT2 et un membre sans dysglycemie > 35 ans (confirmee par une charge en glucose (HGPO) et une mesure d'HbA1c). Les polymorphismes de 70 genes associes au DT2 dans les etudes d'analyse pangenomique (GWAS) ont ete genotypes ou imputes a partir de puces Illumina Infinium HumanCore Beadchips. Ensuite, des analyses familiales de type TDT (Transmission Disequilibrium Test) ont ete realisees. Resultat Nous avons actuellement analyse 54 familles comprenant 113 diabetiques/ prediabetiques (G1=57 ; âge=75,2±8,6 ; IMC=30,1±5,1 / G2=56 ; âge=50,7±8,5 ; IMC=30,7±5,5) et 95 sujets sans dysglycemie a l'HGPO (G1=18 ; âge=68,9±8,1 ; IMC=26,8±4,9 / G2=77 ; âge=48,7±8,4 ; IMC=27,1±5,4). Parmi les genes analyses, 5 variants genetiques etaient nominalement associes ( p Conclusion Certains facteurs genetiques avec la transmission familiale de DT2. La participation a l'enquete Descendance des pharmaciens de la region parisienne permettra de completer les inclusions des familles. Le but final de l'etude sera de disposer d'une equation de risque predictif de la survenue du diabete a l'âge adulte chez des enfants de parents atteints de DT2, a partir de donnees genetiques, epigenetiques et d'environnement familial. Declaration d’interet Les auteurs declarent ne pas avoir d'interet direct ou indirect (financier ou en nature) avec un organisme prive, industriel ou commercial en relation avec le sujet presente.

Introduction La consommation maximale d'oxygene (VO2max) est alteree chez les patients presentant un diabete de type 1 (DT1) mal equilibre. Notre objectif est d'etudier l'impact du DT1 et des niveaux d'hemoglobine glyquee (HbA1c) sur la cascade de l'O2, depuis sa diffusion alveolo-capillaire, son transport arteriel et sa liberation au niveau musculaire, jusqu'a son utilisation mitochondriale. Patients et methodes Des adultes DT1, indemnes de complications, divises en deux groupes (HbA1c n =11 et HbA1c > 8 %, n =12), apparies a des temoins sains, ont effectue 1/ une double diffusion DLCO/DLNO (volume capillaire pulmonaire, conductance de la membrane alveolo-capillaire) 2/ une epreuve d'effort progressive exhaustive incluant des mesures d'oxygenation et d'hemodynamique au niveau du vastus lateralis (spectroscopie du proche infrarouge), du contenu arteriel en O2 et des variables influencant l'hemodynamique et/ou la dissociation de l'oxyhemoglobine (pH ; PaCO2 ; 2,3-DPG ; insuline ; glucose sur prelevements veineux et capillaires arterialises au repos et l'effort maximum). 3/ la respiration mitochondriale etait mesuree (biopsie du vastus lateralis) chez 16 DT1 et leurs temoins. Resultats La VO2max est alteree chez les patients mal equilibres (34,6 ± 7,2 vs 41,2 ± 7,2 ml.min -1 .kg -1 ). La diffusion alveolo-capillaire et le transport arteriel de l'O2 ne different pas entre les groupes. Neanmoins, l'augmentation de l'hemodynamique locale (effet groupe, p p p r =0,47 ; p =0,06 chez les 16 patients). Conclusion Un niveau eleve d'HbA1c dans le DT1 pourrait modifier l'activite du complexe IV de la chaine respiratoire et alterer l'extraction musculaire de l'O2 probablement en raison de l'affinite accrue de HbA1c pour O2. Une moindre perfusion musculaire a l'exercice chez les patients mal equilibres peut etre depistee par spectroscopie du proche infrarouge et suggere l'existence d'alterations fonctionnelles de la microcirculation avant meme l'apparition clinique de microangiopathie. Declaration d’interet Les auteurs declarent ne pas avoir d'interet direct ou indirect (financier ou en nature) avec un organisme prive, industriel ou commercial en relation avec le sujet presente.

Alzheimer's disease (AD) and diabetes mellitus (DM) are two of the most common and devastating health problems in the elderly. They share a number of common features amongst which high prevalence after 65 years, important impact of patient's quality of life, substantial health care costs. Reviews on the epidemiological studies on cognitive impairment in patients with DM found evidence of cross-sectional and prospective associations between type 2 DM and moderate cognitive impairment, on memory and executive functions. There is also evidence for an elevated risk of both vascular dementia and AD in patients with type 2 DM, albeit with strong interaction of other factors such as hypertension, dyslipidaemia and ApoE genotype. DM is an independent predictor of post-stroke dementia. DM being an atherogenic risk factor, it may increase the risk of dementia through associations with stroke, causing vascular dementia. In addition, vascular reactivity may be adversely affected by advanced glycosylation end products resulting in more subtle perfusion abnormalities. Cerebrovascular disease may exacerbate AD through direct interactions between the two pathological processes or through cognitive impairment secondary to cerebrovascular disease "unmasking" AD at an earlier stage than it would otherwise become apparent. The increased risk of AD may also be mediated by the exacerbation of B-amyloid neurotoxicity by advanced glycosylation end products identified in the matrix of neurofibrillary tangles and amyloid plaques in AD brains, or associations with insulin functions. Decreased cholinergic transport across the blood-brain barrier observed in diabetic animals may exacerbate cognitive impairment in AD. Many interventions could reduce the cognitive decline associated with DM, yet not enough are taken into account so far.

To measure ketonemia in a control population of pregnant women and in a population of women with gestational diabetes (GDM). To define a normal ketonemia threshold for the controls and to determine whether or not this value could play a role in the clinical management of women with GDM.Fifty-six women with a normal OGTT and 49 women with GDM were included and monitored from the 25th to the 37th week of pregnancy. Control subjects agreed to perform glycaemia and ketonemia self-monitoring 3 times a day. In addition, women with GDM were asked to measure their postprandial glycaemia. Glycaemia and ketonemia measurements were performed using Optium meters. Subjects kept a 24-hour food record twice a week.The mean ketonemia was lower in the control group than in the GDM group (0.01+/-0.10 vs. 0.04+/-0.009 mmol/l; P0.001). Ketonemia values measured before the midday meal and prior to the evening meal were lower for control subjects than for GDM patients (P=0.002 and P=0.005). Fasting ketonemia was unrelated to ketonuria in the GDM group, whereas there was a correlation in the control group (P=0.006). At least one chronic increase in ketonemia levels was observed in 47% of the women with GDM, compared with only 12% of controls. The lowest levels of evening glycaemia correlated with the highest levels of ketonemia; women with GDM reported lower food and carbohydrate intakes than controls (P0.001).This work has enabled the establishment of ketonemia reference standards in non-diabetic pregnant women. If ketonemia does indeed indicate overly restrictive dietary behavior, this parameter could be employed for monitoring adherence to the nutritional recommendations for GDM.