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Objectives The study aims at evaluating glucose metrics and HbA1C values after pump initiation in outpatient settings. Research design and methods This single center observational study enrolled 121 subjects with type 1 diabetes between September 2020 and May 2021 initiating sensor-augmented pump therapy with stand-alone CGM (n = 26) or pump users who only changed their device (n = 51), with predictive low glucose management (n = 8) or with Hybrid Closed Loop using Medtronic 780G (n = 36) systems. Changes in HbA1C levels and glucose metrics were analyzed after 3 months. All subjects received diabetes and carbohydrate-counting education if needed at time of initiation and were proposed a telehealth monitoring by a diabetic nurse educator. Results There was no episodes of severe hypoglycemia or diabetic ketoacidosis nor serious pump-related adverse events despite outpatient model of care. While only 18/121 (14.8%) participants reached initially the recommended HbA1C levels, 23/85 (27%) in the conventional group and 33/36 (91%) subjects in the Hybrid Closed Loop group reached target levels after 3 months of follow-up. Time in target range 3.9–10 mmol/L (70–180 mg/dl) also improved and was optimal with closed loop with 30/36 (83%) subjects with time in range above 70%. Conclusions Initiation of insulin pump therapy for outpatients is safe with a dedicated facility. Telehealth monitoring after outpatient initiation provides tools for improvement in glucose control with an insulin pump. Outpatient pump initiation is compatible with Hybrid Closed Loop systems which provide the largest improvements in glucose control.

Resume Le diabete de type 1 (DT1) se definit par la necessite de suppleer a la carence de production d’insuline par le pancreas. De nombreux elements experimentaux et cliniques ont permis de correler cette situation clinique qui se manifeste, souvent brutalement, a une destruction selective des cellules s des ilots de Langerhans par un mecanisme auto-immun. Recemment, les etudes histologiques des pancreas de diabetiques et l’amelioration des techniques de mesure du peptide C ont nuance cette affirmation avec, chez certains sujets, la persistance en nombre limite de cellules s fonctionnelles. Cette decouverte surprenante, chez ces sujets micro-secreteurs, remet en cause les dogmes sur la physiopathologie du DT1 et ouvre des perspectives therapeutiques.

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.

International audience; Automated closed-loop (CL) insulin therapy has come of age. This major technological advance is expected to significantly improve the quality of care for adults, adolescents and children with type 1 diabetes. To improve access to this innovation for both patients and healthcare professionals (HCPs), and to promote adherence to its requirements in terms of safety, regulations, ethics and practice, the French Diabetes Society (SFD) brought together a French Working Group of experts to discuss the current practical consensus. The result is the present statement describing the indications for CL therapy with emphasis on the idea that treatment expectations must be clearly defined in advance. Specifications for expert care centres in charge of initiating the treatment were also proposed. Great importance was also attached to the crucial place of high-quality training for patients and healthcare professionals. Long-term follow-up should collect not only metabolic and clinical results, but also indicators related to psychosocial and human factors. Overall, this national consensus statement aims to promote the introduction of marketed CL devices into standard clinical practice.

To assess, in a real-life setting, the effectiveness of telemonitoring adults with type 1 diabetes (T1D) using continuous glucose monitoring in a telemedicine experiment.Experimentation in Telemedicine for the Improvement of Healthcare Pathways (ETAPES), an experimental telehealth programme for five chronic diseases, is supported by the French national healthcare system to promote telemedical care. Using data from a single university hospital centre, 72 adults were studied, including 42 subjects (58%) receiving insulin pump therapy and 30 (42%) receiving multiple daily injections, with a median age of 35.5 years [28.0; 45.0] and poorly controlled type 1 diabetes (T1D) with a mean ± standard error of mean (SEM) HbA1c value of 8.69 ± 0.13%. The primary study outcome was the difference in HbA1c values between baseline and the end of a 6-month follow-up. Other end points of interest were mean blood glucose, glucose management indicator (GMI) level and % time in range (3.9-10 mmol/L) or below or above range.At month 6, mean HbA1c levels were significantly reduced by -0.5% (P 0.001) as were also mean blood glucose levels (P = 0.015), with a significant increase of 6.75 ± 1.36% of time in range at month 3 and of 4.98 ± 1.4% at month 6. Such improvements did not depend on age, gender or type of insulin therapy, but were inversely correlated to initial HbA1c values on multivariate analysis (P 0.001).Although the use of telehealth monitoring offers efficacy and safety in the metabolic control of patients with T1D, it does not fulfil all of these patients' clinical needs. As such, this new healthcare pathway cannot replace, but is a useful complement to, face-to-face in-person clinical visits.

Diabetes mellitus is challenging in the context of the COVID-19 pandemic. The prevalence of diabetes patients hospitalized in intensive care units for COVID-19 is two- to threefold higher, and the mortality rate at least double, than that of non-diabetes patients. As the population with diabetes is highly heterogeneous, it is of major interest to determine the risk factors of progression to a more serious life-threatening COVID-19 infection. This brief review discusses the main findings of CORONADO, a prospective observational study in France that specifically addressed this issue as well as related observations from other countries, mainly China and the US. Some prognostic factors beyond old age have been identified: for example, an increased body mass index is a major risk factor for requiring respiratory assistance. Indeed, obesity combines several risk factors, including impaired respiratory mechanics, the presence of other comorbidities and inappropriate inflammatory responses, partly due to ectopic fat deposits. While previous diabetic microvascular (renal) and macrovascular complications also increase risk of death, the quality of past glucose control had no independent influence on hospitalized diabetes patient outcomes, but whether the quality of glucose control might modulate risk of COVID-19 in non-hospitalized diabetes patients is still unknown. In addition, no negative signs regarding the use of RAAS blockers and DPP-4 inhibitors and outcomes of COVID-19 could be identified. Hyperglycaemia at the time of hospital admission is associated with poor outcomes, but it may simply be considered a marker of severity of the infection. Thus, the impact of glucose control during hospitalization on outcomes related to COVID-19, which was not investigated in the CORONADO study, is certainly deserving of specific investigation.

In the January 2020 issue of Diabetes Care , Soupal et al. (1) provided convincing evidence that continuous glucose monitoring (CGM) by itself is superior to self-monitoring of blood glucose in reducing HbA1c and hypoglycemia, whatever the type of insulin delivery, i.e., continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). Although we agree with the conclusions that CGM is superior to self-monitoring of blood glucose in reducing hypoglycemia, with comparable time below range for MDI and CSII (5.5% and 5.3%, respectively, in their article), we would like to draw …

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since vendredi 13 avril 2018

International audience

This study aimed to assess the efficacy of insulin pumps with automated predictive low-glucose insulin suspension in a real-world setting compared with stand-alone flash glucose monitoring (FGM).The data analyzed were uploaded by patients with type 1 diabetes (n=195) treated with external insulin pumps [either a MiniMed 640G system (Medtronic) including SmartGuard technology that predicts and manages low glucose (n=61) or an Omnipod patch pump accompanied by a FreeStyle Libre sensor (Abbott) for FGM (n=134)].The median (25th-75th percentile) time spent with sensor glucose values≤3.9mmol/L was 0.9% (0.4-1.55) vs. 5.6% (3.05-9.55) in the predictive low-glucose suspend group vs. FGM users, respectively (P0.0001), with similar results obtained for median time spent with sensor glucose values≤3mmol/L (P0.0001). The group using sensor-integrated pumps had lower % coefficient of variation (CV) values and lower mean amplitude glycaemic excursions (P0.0001). Mean glucose values as well as measured HbAThese real-world data show that predictive low-glucose insulin suspension is more effective than pumps with stand-alone FGM for reducing hypoglycaemic events, and could be of benefit to patients at risk of hypoglycaemia as well as those lacking in hypoglycaemic awareness.

Background.The use of miRNAs as biomarkers for Type 1 Diabetes (T1D) risk is attractive as T1D is usually diagnosed in front of acute symptoms. As miR-375 is highly expressed in the endocrine pancreas, we postulated that its circulating level might reflect beta cell alterations and might be altered in the blood of T1D patients recently diagnosed.Methods.Sera were obtained from 22 T1D children at onset of the disease, before subcutaneous insulin treatment, and from 10 nondiabetic pediatric controls. MiR-375 seric level was quantified by stem-loop RT-PCR-based assay. MiRNAs regulations in isolated human islets in response to high glucose concentrations were determined by TaqMan Low-Density Array.Results.The abundance of miR-375, among the 410 miRNAs detected in human islets, mirrored its well-established role in rodent islet biology. Upregulated miRNAs targeted genes involved in islet homeostasis and regulation of beta cell mass. Downregulated miRNAs, including miR-375, were involved in pancreas secretion and protein turnover. Seric level of miR-375 was lower in T1D children versus age-matched controls, without any correlations with HbA1c, glycaemia, and number of autoantibodies.Conclusion.Altered circulating level of miR-375 at onset of T1D might be a general biomarker of metabolic alterations and inflammation associated with the disease.

OBJECTIVE Pancreatic scintigraphy with interleukin-2 radiolabeled with 99mTc (99mTc-IL-2) is a technique used to image chronic inflammatory-mediated disorders. We used this method to detect a signal consistent with the presence of insulitis in patients with autoimmune diabetes. Positive and negative controls (patients with pancreatic carcinoma and type 2 diabetes, respectively) also were studied. RESEARCH DESIGN AND METHODS We examined 25 patients with autoimmune diabetes (16 with recently diagnosed type 1 diabetes, 9 with latent autoimmune diabetes in adults [LADA]), 6 with type 2 diabetes, and 7 with pancreatic carcinoma (the latter two groups were used as negative and positive controls, respectively). All patients underwent 99mTc-IL-2 scintigraphy and contrast-enhanced MRI of the pancreas. To validate positive controls, samples were taken from patients with pancreatic carcinoma during surgery for histological and immunohistochemical investigations. RESULTS Pancreatic accumulation of 99mTc-IL-2 was detected in patients with autoimmune diabetes (61% positive) and, notably, in 6 of 9 patients with LADA; semiquantitative evaluation of pancreatic uptake of 99mTc-IL-2 showed higher values in patients with autoimmune diabetes (both childhood and LADA) and pancreatic carcinoma than in those with type 2 diabetes (4.45 ± 1.99, 4.79 ± 1.1, and 4.54 ± 1.62 vs. 2.81 ± 0.63; P = 0.06, P = 0.01, and P = 0.04, respectively). In patients with pancreatic carcinoma, pancreatic interleukin-2 receptor expression correlated with pancreatic 99mTc-IL-2 uptake (r = 0.8; P = 0.01). In patients with LADA, 99mTc-IL-2 uptake inversely correlated with duration of disease (r = 0.7; P = 0.03). CONCLUSIONS Autoimmune diabetes in adults is associated with increased pancreatic 99mTc-IL-2 uptake, indicating the presence of insulitis, particularly within 1 year of the beginning of insulin therapy, similar to type 1 diabetes at diagnosis.

International audience; Background Islet transplantation is indicated for patients with type 1 diabetes with severe hypoglycaemia or after kidney transplantation. We did a randomised trial to assess the efficacy and safety of islet transplantation compared with insulin therapy in these patients. Methods In this multicentre, open-label, randomised controlled trial, we randomly assigned (1:1) patients with type 1 diabetes at 15 university hospitals to receive immediate islet transplantation or intensive insulin therapy (followed by delayed islet transplantation). Eligible patients were aged 18-65 years and had severe hypoglycaemia or hypoglycaemia unawareness, or kidney grafts with poor glycaemic control. We used computer-generated randomisation, stratified by centre and type of patient. Islet recipients were scheduled to receive 11000 islet equivalents per kg bodyweight in one to three infusions. The primary outcome was proportion of patients with a modified (beta-score (in which an overall score of 0 was not allocated when stimulated C-peptide was negative) of 6 or higher at 6 months after first islet infusion in the immediate transplantation group or 6 months after randomisation in the insulin group. The primary analysis included all patients who received the allocated intervention; safety was assessed in all patients who received islet infusions. This trial is registered with ClinicalTrials.gov, number NCT01148680, and is completed. Findings Between July 8, 2010, and July 29, 2013, 50 patients were randomly assigned to immediate islet transplantation (n=26) or insulin treatment (n=24), of whom three (one in the immediate islet transplantation group and two in the insulin therapy group) did not receive the allocated intervention. Median follow-up was 184 days (IQR 181-186) in the immediate transplantation group and 185 days (172-201) in the insulin therapy group. At 6 months, 16 (64% [95% CI 43-82]) of 25 patients in the immediate islet transplantation group had a modified (beta-score of 6 or higher versus none (0% [0-15]) of the 22 patients in the insulin group (p\textless0.0001). At 12 months after first infusion, bleeding complications had occurred in four (7% [2-18]) of 55 infusions, and a decrease in median glomerular filtration rate from 90-5 mL/min (IQR 76-6-94-0) to 71-8 mL/min (59-0-89-0) was observed in islet recipients who had not previously received a kidney graft and from 63 .0 mL/min (55.0-71-0) to 57. 0 mL/min (45-5-65 . 1) in islet recipients who had previously received a kidney graft. Interpretation For the indications assessed in this study, islet transplantation effectively improves metabolic outcomes. Although studies with longer-term follow-up are needed, islet transplantation seems to be a valid option for patients with severe, unstable type 1 diabetes who are not responding to intensive medical treatments. However, immunosuppression can affect kidney function, necessitating careful selection of patients. Copyright (C) 2018 Elsevier Ltd. All rights reserved.

International audience

Objective The International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines for gestational diabetes mellitus (GDM) diagnosis determines that fasting, 1-h and 2-h glucose values may contribute independently to adverse outcomes. However, given the different physiological bases of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), differences in pregnancy outcomes are to be expected. This study aimed to determine whether classification of GDM women according to glucose homoeostasis results in heterogeneity in maternal and/or fetal outcomes. Material and methods Of the 75 pregnant women included after a 75-g 2-h OGTT performed between weeks 24–32 of gestation as per WHO criteria, 55 were classified as GDM (16 with IFG and 39 with IGT) according to IADSPG criteria. Their anthropometric and metabolic characteristics were compared with those of non-GDM women with IFG or IGT. Maternal and neonatal outcomes were prospectively recorded for each group. Results GDM women with IFG, including isolated IFG and combined IFG + IGT, were significantly heavier, had higher leptin values and were more frequently multiparous than GDM women with isolated IGT. HOMA-IR was significantly higher when fasting glucose was impaired. There were no significant differences in maternal outcomes according to metabolic status. In addition, large for gestational age (LGA) neonates were significantly seen more often in the IFG group. Fasting glucose was significantly associated with LGA independently of BMI and 2-h OGTT glucose. The > 5.1 mmol/L cut-off value for fasting glucose was highly predictive of delivery of LGA infants. Conclusion IFG in GDM women was associated with increases in BMI, fat mass and hepatic insulin resistance. Delivery of LGA neonates was more frequent when fasting glycaemia was increased during the third trimester of pregnancy, and was independent of BMI and 2-h OGTT glucose values.

Type 2 diabetes (T2D) remission after bariatric procedures has been highlighted in many retrospective and some recent prospective studies. However, in the most recent prospective study, more than 50 % of patients did not reach T2D remission at 1 year. Our aim was to identify baseline positive predictors for T2D remission at 1 year after bariatric surgery and to build a preoperative predictive score. We analysed the data concerning 161 obese operated on between June 2007 and December 2010. Among them, 46 were diabetic and were included in the study-11 laparoscopic adjustable gastric banding (LAGB), 26 Roux-en-Y gastric bypass (RYGB) and 9 sleeve gastrectomy (SG). We compared anthropometric and metabolic features during 1 year of follow-up. A receiver operating characteristic analysis was performed to predict T2D remission. RYGB and SG were similarly efficient for body weight loss and more efficient than LAGB; 62.8 % of patients presented with T2DM remission at 1 year, with no significant difference according to the surgical procedure. A 1-year body mass index (BMI)35 kg m(-2) was predictive of T2DM remission whatever the procedure. The preoperative predictive factors of diabetes remission were baseline BMI ≤50 kg m(-2), duration of type 2 diabetes ≤4 years, glycated haemoglobin ≤7.1 %, fasting glucose1.14 g/l and absence of insulin therapy. A short duration of diabetes and good preoperative glycaemic control increase the rate of T2DM remission 1 year after surgery. Preoperative metabolic data could be of greater importance than the choice of bariatric procedure.

International audience; Type 2 diabetes is characterized by peripheral insulin resistance and pancreatic beta cell dysfunction. Elevated free fatty acids (FFAs) may impair beta cell function and mass (lipotoxicity). Altered calcium homeostasis may be involved in defective insulin release. The endoplasmic reticulum (ER) is the major intracellular calcium store. Lipotoxicity induces ER stress and in parallel an ER calcium depletion through unknown ER calcium leak channels. The main purposes of this study is first to identify one of these channels and secondly, to check the opportunity to restore beta cells function (i.e., insulin secretion) after pharmacological inhibition of ER calcium store depletion. We investigated the functionality of translocon, an ER calcium leak channel and its involvement on FFAs-induced alterations in MIN6B1 cells and in human pancreatic islets. We evidenced that translocon acts as a functional ER calcium leak channel in human beta cells using anisomycin and puromycin (antibiotics), respectively blocker and opener of this channel. Puromycin induced a significant ER calcium release, inhibited by anisomycin pretreatment. Palmitate treatment was used as FFA model to induce a mild lipotoxic effect: ER calcium content was reduced, ER stress but not apoptosis were induced and glucose induced insulin secretion was decreased in our beta cells. Interestingly, translocon inhibition by chronic anisomycin treatment prevented dysfunctions induced by palmitate, avoiding reticular calcium depletion, ER stress and restoring insulin secretion. Our results provide for the first time compelling evidence that translocon actively participates to the palmitate-induced ER calcium leak and insulin secretion decrease in beta cells. Its inhibition reduces these lipotoxic effects. Taken together, our data indicate that TLC may be a new potential target for the treatment of type 2 diabetes.

Resume L’evolution des technologies de suivi et de traitement du diabete de type 1 repose, en particulier, sur la mesure continue du glucose couplee a la perfusion continue d’insuline par pompe. Nous rapportons une etude pilote menee chez des patients diabetiques de type 1 a haut risque d’hypoglycemies severes, beneficiant du nouveau systeme de pompe a insuline et capteur de glucose avec la fonction arret automatique en cas d’hypoglycemie (AAH). Cette etude multicentrique a porte sur 14 patients, sur une periode de temps allant de quelques jours a plusieurs semaines. Treize patients sur 14 ont presente au moins un episode d’AAH, soit un total de 221 evenements AAH et une incidence cumulee de 0,36 AAH/patient/jour. La frequence mediane est de 0,15 AAH/jour. La majorite des AAH a dure moins de 5 minutes, mais 12 % des AAH se sont prolonges sur une periode maximale de 120 minutes. Ils representent 8 % des AAH diurnes (6h00-minuit) et 32 % des AAH nocturnes (minuit-6h00) ( p

Resume La mise en evidence de biomarqueurs, notamment auto-anticorps circulants, caracterise le processus auto-immun conduisant au diabete de type 1 et autorise un depistage, notamment dans les familles de diabetiques ou la sensibilite du depistage est meilleure du fait du terrain genetique. Les essais de prevention reposent sur des approches d’immuno-intervention et la quete d’une possible induction de tolerance. La protection et/ou la regeneration des cellules β sont devenues un enjeu majeur. La possibilite de modulation des marqueurs d’auto-immunite anti-ilots chez les patients par ces approches rend relativement optimiste sur la possibilite d’une approche, probablement combinee, vers une immunotherapie efficace de la maladie.

L’accumulation de produits avances de glycation (AGE) au niveau tissulaire apparait comme un element physiopathologique – communement appele phenomene de « memoire glycemique » – evoque dans les etudes prospectives de suivi des complications diabetiques UKPDS et DCCT/EDIC. La mesure des produits AGE montre une tres bonne correlation avec la survenue des complications degeneratives du diabete, de facon independante a la mesure de l’HbA1c. Le developpement de systemes permettant la mesure non invasive des AGE cutanes par autofluorescence apporte un nouvel eclairage dans la relation niveau glycemique et complications chez le patient diabetique. Dans le domaine du risque individuel, particulierement heterogene, cette technique permet d’identifier des sujets a risques metabolique et cardiovasculaire. Quelques etudes suggerent aussi une bonne correlation entre cette mesure et les complications de microangiopathie. Il reste a determiner, par des etudes prospectives, la valeur predictive positive et negative de cette mesure afin d’inclure son utilisation en pratique courante dans le suivi de patients diabetiques.

Advanced glycation end products (AGEs) are thought to play a central role in the pathogenesis of diabetes complications. For this reason, a non-invasive tool using skin autofluorescence (AF) quantification that correlates with levels of tissue AGEs has been developed. The present study aimed to assess whether or not skin AF is associated with microvascular complications in patients with type 1 diabetes (T1D).All consecutive patients with T1D (n=133) had three AF measures taken on the forearm, using illumination with a fluorescent tube, all on the same day after breakfast or lunch. Potential associations between skin AF levels and microvascular complications, age, diabetes duration and health status were then assessed using a multivariate linear-regression model.On age-adjusted analyses, diabetes duration, retinopathy, nephropathy and neuropathy were significantly associated with skin AF levels (all P0.001). AF levels increased significantly with severity in both retinopathy and nephropathy (P0.001). After adjusting for age, diabetes duration, HbA(1c), smoking, retinopathy, nephropathy and neuropathy, the association of AF levels remained significant with nephropathy and neuropathy, but not with retinopathy and diabetes duration.This study suggests an independent association between skin AF levels and diabetic nephropathy and neuropathy, but not retinopathy, in T1D patients. Prospective studies are needed to confirm the ability of skin AF levels to predict microangiopathy.

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.

Purpose To evaluate the sensitivity and specificity of one- and three-field, nonmydriatic and mydriatic, and 45° digital colour photography compared with mydriatic indirect ophthalmoscopy for diabetic retinopathy (DR) screening. Methods A group of 79 patients (158 eyes) were included in this prospective study. Colour fundus photographs were taken with a Topcon TRC-NW6S digital camera, using four different techniques—single-field nonmydriatic; three-field nonmydriatic; single-field mydriatic; and three-field mydriatic—followed by dilated ophthalmoscopy. Two independent ophthalmologists classified blinded photographs according to the presence or absence of specific diabetic retinal findings. The sensitivity, specificity and agreement (kappa analyses) of the four methods were calculated for the presence or absence of DR and for all diabetic retinal findings. Results The sensitivity and specificity of digital photography compared with ophthalmoscopy for detection of DR were, respectively: 77 and 99% using single-field nonmydriatic; 92 and 97% using three-field nonmydriatic; 90 and 98% using single-field mydriatic; 97 and 98% using three-field mydriatic. The degrees of agreement for the four methods were 0.82, 0.90, 0.90 and 0.95, respectively. For specific retinal findings, sensitivity was greater for detection of hard exudates, nerve fibre layer haemorrhage and venous beading, and lower for detection of microaneurysms, dot-blot haemorrhage, cotton wool spots and intraretinal microvascular anomalies. Conclusion The three-field strategy without pupil dilation represents a good compromise, with reasonable sensitivity and good comfort (short examination duration, able to drive after photography) favouring patient compliance with the screening programme.

Resume Introduction Nous avons evalue l’interet de la tomographie par emission de positons (TEP) au 18F-fluoro-deoxyglucose (18FDG) pour la recherche d’une neoplasie occulte devant une suspicion de syndrome paraneoplasique (SP). Methode Une TEP au 18FDG a ete realisee chez 31 patients, cliniquement suspects d’avoir un SP. Les SP etaient au nombre de 34 dont 12 maladie neurologique, huit endocriniennes, sept rhumatologiques, une dermatologique et six vasculaires. Nous avons compare les resultats d’une tomodensitometrie (TDM) et de la TEP aux conclusions finales des cliniciens portees au terme du bilan et d’une periode de suivi d’au moins deux mois. Resultats Nous avons obtenu une preuve histologique de cancer pour dix patients, mais n’avons pu identifier le site primitif pour seulement neuf d’entre eux. La TEP a mis en evidence six sites primitifs dont trois qui n’avaient pas ete visualises en TDM. La TDM a mis en evidence quatre sites primitifs dont un qui n’a pas ete visualise en TEP. Dans un cas, la TEP a montre des metastases ganglionnaires alors que celles-ci n’avaient pas ete identifiees par la TDM. Onze causes benignes ont ete conclues parmi lesquelles la TEP a joue un role majeur dans trois cas. Dix causes restent indeterminees a la fin de l’etude. Conclusion La TEP joue un role important dans l’identification d’une neoplasie occulte, devant une suspicion de syndrome paraneoplasique soit en identifiant le site primitif, soit en guidant la biopsie d’eventuelles metastases. De plus, elle peut permettre de reveler des causes non neoplasiques.

Clinical protocols in type 1 diabetic patients to optimize islet survival and function post-transplantation improved dramatically in the last decade, but it is clear that this approach still has potential limitations to provide long term insulin independency. Islet allografts administered in the liver via the portal vein are exposed to several factors contributing to a rapid loss of function that may reach 50% of the initial beta cell mass. Allo- and auto-immune reactions - an unique situation in clinical transplantation - are partially overcome with immunosuppressive regimen. Serological markers and T cell reactivities may correlate with graft failure. Most of the drugs that are used, including rapamycin (sirolimus) or the calcineurin inhibitor tacrolimus (FK506), have deleterious effects on beta function and/or insulin sensitivity. Immediate factors that limit initial islet engraftment have been elucidated, including instant blood mediated inflammatory reaction and angiogenesis. Newer interventions designed to promote islet survival, to prevent apoptosis, to promote islet growth and to protect islets in the long run from immunological injury are rapidly approaching clinical trials.

Resume Une patiente de 56 ans presente un diabete depuis l’âge de 24 ans. Il faudra attendre la decouverte du gene de la lamine A/C, 20 ans plus tard, pour faire le diagnostic de lipodystrophie partielle familiale de type 2 ou syndrome de Dunnigan. Le tableau clinique associe un diabete avec une lipodystrophie, des anomalies de la conduction cardiaque et une dystrophie musculaire avec myalgies.

Introduction Les syndromes d'insulino-resistance extreme sont un ensemble de pathologies rares d'etiologies diverses. Patients et Methodes Nous rapportons le cas d'un diabete de nosologie indeterminee avec insulinoresistance extreme et decompensation acidocetosique survenue 10 ans apres le diagnostic initial. Observations Il s'agit d'un patient de 83 ans, normoponderal, avec des besoins insuliniques tres eleves mais variables au cours du nycthemere, avec des debits insuliniques pouvant atteindre 100 UI/h au pousse-seringue electrique dans la journee, contrastant avec des debits de 0,3 a 3 UI/h d'insuline la nuit avec la survenue d'hypoglycemies nocturnes. Ce syndrome d'insulino-resistance extreme etait associe avec la presence d'anticorps anti-insuline a titre tres eleve, superieurs a 90 %, en l'absence d'anticorps anti-recepteur a l'insuline. Un syndrome lymphoproliferatif B a immunoglobuline M de type lymphome lymphocytique a pu etre diagnostique. Le patient a beneficie de 3 echanges plasmatiques et de 3 cures de chimiotherapie associant du Rituximab, du Cyclophosphamide et de la Methylprednisolone. Ces traitements ont permis une amelioration rapide et spectaculaire de l'insulinoresistance avec un bon equilibre glycemique sous 34 UI d'insuline par jour avec en parallele une diminution du taux des anticorps anti-insuline et une regression du pic monoclonal d'immunoglobuline M. Quatorze mois apres la fin de la chimiotherapie, il a presente une recidive du syndrome lymphoproliferatif B avec une reapparition de son insulino-resistance extreme, qui ont regresse apres une nouvelle ligne de chimiotherapie. Conclusions Ce cas tres rare d'insulino-resistance extreme illustre la relation entre insulino-resistance, anticorps anti-insuline et hemopathie maligne. En pratique clinique, il apparait important de controler les anticorps anti-insuline en cas d'apparition recente d'une insulino-resistance extreme et de rechercher, en cas de positivite, une hemopathie sous-jacente. Le traitement de l'insulinore-sistance est lie a celui de l'hemopathie.

International audience; AIMS: To describe oesophageal function in people with diabetes and poor glycaemic control using oesophageal high-resolution manometry and to compare the result between control subjects and patients with gastro-oesophageal reflux disease. METHODS: The results of oesophageal high-resolution manometry and a gastric emptying test were reviewed in 20 patients with diabetes. The high-resolution manometry protocol consisted of 5-ml swallows of water and multiple swallows of water. Oesophageal motility disorders were classified according to the Chicago classification system. The occurence of multiphasic contractions and intragastric and intrabolus pressures were measured. High-resolution manometry results were compared between 10 control subjects and 20 patients with gastro-oesophageal reflux disease. Data were expressed as medians and compared using Mann-Whitney and chi-squared tests. RESULTS: Oesophageal motility disorders were similarly distributed between the groups. Multiphasic contractions occurred more frequently in patients with diabetes than in those with gastro-oesophageal reflux disease (60 vs 20% per patient; P\textless0.01) and were not observed in control subjects. Gastric emptying was delayed in six patients with diabetes and did not correlate with symptoms or oesophageal motility disorders. Intrabolus pressure was higher in patients with diabetes and gastroparesis than in those without (17 vs 10 mmHg; P=0.02) and correlated with intragastric pressure (r=0.46, P\textless0.01). During multiple swallows of water, oesophageal contractile activity was incompletely inhibited in 83% of patients with diabetes and gastroparesis vs 9% without (P\textless0.01). Oesophageal function and gastric emptying were not influenced by fasting glycaemia. CONCLUSIONS: Patients with gastroparesis might present with impaired inhibition of contractile activity during multiple swallows of water. Increased intrabolus pressure is suggestive of delayed oesophageal clearance as a consequence of gastroparesis.

Aims Diabetic foot osteomyelitis is an important risk factor of lower limb amputation. Antibiotic therapy is often effective in preventing surgery. However, the duration of antibiotic therapy is difficult to define in the absence of a marker to diagnose osteomyelitis remission at the end of the treatment. In this study, we assessed the diagnostic performance of white blood cell SPECT/CT imaging for evaluating osteomyelitis remission. Patients and methods Twenty-nine out of 42 episodes of diabetic foot osteomyelitis seen between December 2009 and April 2012 had radiographs, a three-phase bone scintigraphy and a white blood cell SPECT/CT at the end of antibiotic therapy. They were treated with antibiotics alone and considered in clinical remission. White blood cell SPECT/CT results were considered positive when abnormal uptake in the osteomyelitis location was identified. Osteomyelitis remission was defined by the absence of an osteomyelitis relapse after 12 months’ follow-up. Results A negative white blood cell SPECT/CT was seen for 22 episodes of osteomyelitis. All of them were in remission. A positive white blood cell SPECT/CT was observed for seven episodes. A relapse occurred in five episodes (71.5%) after a median duration of 4 months (2–7 months). Sensitivity, specificity, positive predictive value and predictive negative value in predicting osteomyelitis relapse after the discontinuation of antibiotic treatment were, respectively, for radiographs 80%, 33%, 20% and 89%; for three-phase bone scintigraphy 100%, 12.5%, 15.5% and 100%; and for the white blood cell SPECT/CT 100%, 91.5%, 71.5% and 100%. Conclusion Negative uptake on white blood cell SPECT/CT is a good marker for diagnosis of diabetic foot osteomyelitis remission and might be very useful in guiding antibiotic therapy.

OBJECTIVE: In type I diabetes mellitus, early markers of beta cell damage are needed in order to detect the infraclinical development of the disease. The reg protein may be a good candidate, as the reg gene has been proposed to play a role in the pancreatic beta cell destruction/regeneration process during diabetogenesis in animal models of autoimmune diabetes. The aim of this study was to test the hypothesis whether serum reg protein level could be representative of either the destructive or regenerative process at the beta cell level during the early phases of type I diabetes in humans. DESIGN AND METHODS: We used a highly specific immunoassay to measure serum reg protein level in controls and in three groups of either diabetes prone or diabetic subjects: recently diagnosed diabetic patients, long-standing diabetic patients and islet cell antibody-positive non-diabetic subjects. RESULTS: We found no significant difference between the values observed in these three groups in comparison with control group (90.7+/-18.1ng/ml, 83.1+/-5.6ng/ml, 98.7+/-24.5ng/ml vs 85.5+/- 5.6ng/ml respectively). Moreover, when the insulin reserve was evaluated at 6 months in the recently diagnosed group, serum reg protein levels were not different between patients with or without residual insulin secretion (at onset: 103+/-42 vs 70.3+/-8. 5ng/ml respectively; at 6 months: 79.7+/-25.8ng/ml vs 81.6+/-15ng/ml respectively). In contrast, trypsin levels were significantly lower in every group of diabetic patients. Results were expressed as means +/- S.E.M. and groups compared by Student's t-test (P

We describe here the unusual aggregation of diabetes cases in a family of 10 subjects. Among them, three adult siblings presented with LADA and one child presented with juvenile type 1 diabetes. Although the exact pathogenesis of LADA is unknown and questions the role of autoimmunity in β cell failure, the familial aggregation of these two forms of diabetes underlines the existence of common roots, i.e. immune mechanisms and genetic susceptibility. This report clearly illustrates the differences in terms of autoimmunity (prevalence and titer of GAD and IA2 antibodies) and HLA class II genotype between patients with LADA and those with juvenile type 1 diabetes.

The selective destruction by an autoimmune process of the beta cells in the pancreas is the hallmark of the type 1 insulin-dependent diabetes mellitus. What triggers islet cell-specific autoreactive T and B cells, however, remains unclear. Identification of the targets of the anti-islet cell autoantibodies frequently found in insulin-dependent diabetes mellitus patients and analysis of their sequences should provide some insights into the nature of this disease. We have combined EBV transformation with CD40 activation of peripheral B cells from one patient with insulin-dependent diabetes mellitus to isolate four B cell clones that secrete islet cell-specific autoantibodies, These four human monoclonal autoantibodies are of the IgG1 isotype, and they each recognize a different epitope of the glutamic acid decarboxylase enzyme. Analysis of their variable gene sequences shows that, while clonally unrelated, three of the four human monoclonal autoantibodies use a member of the VH4 family, and two have rearranged the same delta light chain variable gene. The IgG1 isotype of the four autoantibodies as well as the presence of somatic mutations in both heavy and light chain genes provide concrete evidence for their derivation by a T cell-dependent immune response.

Introduction Les mutations du canal potassique ATP sensible (canal K+ATP) sont une cause frequente de diabete neonatal (NDM), transitoire (TNDM) ou permanent (PNDM). Dans les PNDM par mutation du canal K+ATP, l'insulinotherapie peut etre arretee au profit d'un traitement par sulfamides hypoglycemiants. Notre objectif etait de decrire une serie de cas de NDM par mutation du canal K+ATP. Patients et Methodes Huit patients suivis pour un NDM par mutation du canal K+ATP ont ete inclus. Les donnees cliniques et biologiques relatives a la decouverte, a l'evolution et a l'eventuelle tentative de relais par sulfamides ont ete recueillies et analysees. Observations Sept enfants atteints par mutations d'ABCC8 et un adulte par mutation de KCNJ11 ont ete inclus. Aucun ne presentait d'anticorps du diabete de type 1, de complication du diabete, ou de syndrome DEND. Deux sujets presentaient un TNDM, dont un a presente une recidive traitee par sulfamides. Parmi les six PNDM, le relais par sulfamides a permis l'arret de l'insuline chez cinq sujets ; le patient insulinodependant semblait presenter un PNDM plus severe. Le traitement par sulfamides restaurait une insulinosecretion, objectivee par la mesure du peptide C a jeun et post-stimulation ; et permettait un bon equilibre glycemique, au vu de l'HbA 1c et des glycemies capillaires. Plusieurs semaines etaient necessaires pour definir la dose de sulfamides adaptee au patient ; la dose a l'introduction et la dose maximale utilisee etaient respectivement au moins deux fois et trois fois plus elevees que la dose finalement necessaire. Conclusions Les mutations d'ABCC8 etaient majoritaires dans notre echantillon. Le controle de l'HbA 1c apres relais etait conserve, et l'instabilite glycemique diminuee. Les modalites de relais par sulfamide (dose initiale, vitesse d'augmentation) et ses indications (severite de la mutation, insulino-secretion residuelle) beneficieraient a etre plus documentees, notamment par une mesure continue du glucose et une courte hospitalisation avec test au glucagon avant et apres l'introduction des sulfamides.

Introduction La greffe d'ilots pancreatiques (GIP) est une alternative therapeutique du diabete de type 1 instable. Or seulement 44 % des patients sont insulino-independants a 3 ans. L'apparition d'allo-anticorps (anti-HLA classe I et II) est parfois correlee a la dysfonction des ilots mais cette association n'a pas ete retrouvee par toutes les etudes. L'objectif de ce travail est d'etudier (I) l'evolution de la reponse humorale allo specifique apres GIP et (II) son lien avec la dysfonction du greffon. Patients et Methodes Parmi 122 patients greffes d'ilots de 2000 a 2013 (reseau GRAGIL), 45 patients pour qui nous disposions d'un serum pre-greffe et annuel post-greffe ont ete inclus retrospectivement. Les anticorps anti-HLA specifique du donneur (ASD) etaient detectes par methode singleantigen (Immucor©), leur titre evalue par la MFI et leur capacite a activer le complement par le test du « C3d-binding ». Nous avons analyse le delai de survenue d'une dysfonction du greffon (perte de 50 % du gain de β-score post-greffe) a compter de la date de leur apparition comparativement a l'evolution en l'absence d'ASD. Resultats Les caracteristiques initiales des patients ayant ou non developpe des ASD etaient comparables : IEQ moyen : 11 991 ± 582 IEQ/kg, HbA1c pre greffe = 8,1 % ± 0,3 %. 16 patients avaient beneficie d'une autre greffe auparavant (rein, pancreas). 13/45 patients ont developpe des ASD dont 2 avec non fonction primaire du greffon. Pour 3/11 patients les ASD sont apparus tardivement apres la perte de fonction du greffon et baisse de l'immunosuppression, 5/11 patients ont presente une dysfonction apres l'apparition des ASD et 3/11 n'ont pas presente de dysfonction a la fin du suivi. L'intensite de la reponse humorale etait heterogene (MFI 400–9600). Aucun ASD ne fixait le complement. A trois ans, 22,8 % des patients sous immunosuppresseurs developpaient des ASD contre 80 % apres l'arret des immunosuppresseurs. Conclusions L'apparition d'ASD apres GIP survient chez un tiers des patients. Si l'impact de ces anticorps sur la fonction du greffon reste incertain dans cette etude, leur presence pose le probleme de l'acces a une pro-chaine greffe.

Introduction Le diabete de type 2 s'accompagne d'une diminution de la masse des cellules beta. Les mitochondries et le reticulum endoplasmique (RE) sont des organites importants pour la synthese et l'exocytose de l'insuline qui interagissent pour echanger du calcium via le complexe IP3R/ Grp75/VDAC. Pour la premiere fois, nous avons etudie l'expression de proteines cles de l'homeostasie calcique du RE et des mitochondries et leurs interactions, dans le pancreas de diabetiques de type 2 et de sujets controles. Materiels et Methodes Des coupes en paraffine obtenues a travers le consortium nPOD (Network for Pancreatic Organ donors with diabetes) provenant de diabetiques de type 2 (DT2, n =11) et de sujets controles ( n =10), ont ete etudiees par immunohistochimie en microscopie confocale ou avec un scanner de lames. Nous avons rapporte le niveau d'expression de proteines du RE ou de la mitochondrie au sein des cellules marquees pour l'insuline. Nous avons aussi quantifie le nombre de zones d'interactions Resultats L'intensite moyenne pour IP3R-2 dans les cellules beta etait significativement plus importante chez les DT2 de meme que celle de TOM20, un recepteur peptidique de la membrane externe de la mitochondrie. Individuellement, l'intensite de TOM20 n'etait pas correlee avec IP3R-2 mais avec le cytochrome C, proteine de la chaine respiratoire mitochondriale. Le marquage de la Cyclophiline D, une isomerase de la matrice mitochondriale qui regule les interactions et le transfert de calcium du RE vers la mitochondrie, etait significativement plus faible chez les DT2. A l'exception d'un donneur DT2 presentant une lipomatose importante du pancreas exocrine, le nombre de spots de ligation IP3R-2/VDAC-1 par cellules d'ilot, etait significativement plus faible chez les DT2 (0,48+0,03 vs 0,9+0,04, p Conclusions Nous confirmons chez l'homme l'importance des interactions mitochondries-RE et probablement de l'homeostasie calcique dans la fonction des cellules beta, donnant ainsi une base moleculaire des anomalies fonctionnelles qui precedent la reduction de la masse de cellules beta au cours du DT2.

In this report we describe a patient who, after allogeneic bone marrow transplantation from her HLA-identical sister, developed polyendocrine failure in the form of Type 1 (insulin-dependent) diabetes mellitus and hypothyroidism. This was the result of the transfer of donor lymphoid cells which were activated by allogeneic bone marrow transplantation. The full chimerism of the recipient was demonstrated by restriction fragment length polymorphism analysis from nucleated blood cells and fibroblast DNA. During the 9-year follow-up, the donor developed hypothyroidism and signs of pre-Type 1 diabetes. This clinical observation resembles the adoptive transfer of diabetes observed in non-obese-diabetic mice and BB rats and confirms the role of immune processes in the pathogenesis of this disease.

Factors associated with diabetes onset were analysed for their predictive value in 708 first-degree relatives of Type 1 (insulin-dependent) diabetic patients including 374 parents and 308 siblings of Type 1 diabetic patients. Relatives were prospectively followed for 2 304 subject years with blood samples for specific autoantibody evaluation. Islet cell cytoplasmic autoantibody titres were quantified in Juvenile Diabetes Foundation units with a threshold of positivity of 5 units. Insulin autoantibodies were determined using Tyr-A14 iodinated human insulin. HLA typing was performed in 92% of the relatives. During the time of study, 17 of 646 (2.6%) relatives showed islet cell antibodies. During follow-up, eight relatives developed diabetes, including six with high islet cell antibody titre. Taking titres above 20 units increased the positive predictive value from 35% to 75% whereas the presence of insulin autoantibodies did not increase the positive predictive value for the disease. Analysis of metabolic profiles months before the onset of diabetes by either oral or intravenous glucose loads, indicated a considerable level of heterogeneity with relatives with a high islet cell antibody titre who rapidly developed insulin-dependent diabetes, whereas others remained insulin-independent during the same observation period despite comparable titres. This study clearly indicates that initial islet cell antibody titre is not sufficient to predict individual outcome. Follow-up samples are clearly needed to monitor progression of the disease. Few relatives with persistent immunologic positivity progress to clinical Type 1 diabetes, suggesting that non-progressive and sub-clinical Beta-cell dysfunction is common. Despite current knowledge and available genetic and immune markers, early identification of the relatives progressing to clinical diabetes is still difficult and does not allow at the present time aggressive immunointervention at the prediabetic stage.

The adoptive transfer of type I diabetes in nonobese diabetic mice requires the contribution of both CD4+ and CD8+ T cells. To further elucidate the cellular pathway(s) of beta-cell destruction and the responsibility of each subset, high doses of committed T cells from diabetic mice purified to single subsets, were injected into syngeneic nonobese diabetic neonates. The recipients of single or mixed subsets were followed for clinical manifestations of diabetes and examined at 30 days of age for in situ lesions. None of the animals injected with either CD4+ or CD8+ T cells became overtly diabetic during the 30 days of observation whereas 8 of 23 mice inoculated with a mixture of the two subsets developed glycosuria and hyperglycemia. However, insulitis was found in 6 of the 13 mice injected with CD4+ T cells whereas only 1 of the 9 mice injected with CD8+ T cells showed marginal infiltration of the pancreas. The lesions initiated by CD4+ T cells alone were considerably less severe than those induced by the mixture of both subsets, corroborating the fact that overt disease did not occur in the former group. Together, these results suggest a distinct function for each diabetogenic T cell subset. CD4+ T cells, which have the capacity to home to the pancreas, promote in turn the influx of CD8+ effector T cells that do not by themselves accumulate in this organ. These results illustrate a novel form of T-T cell interactions leading to organ specific autoimmune lesions.

To find a simple and reliable means to measure vibration sensations, 189diabetic patients and 88 control subjects were tested at different sites with a graduated tuning fork. Within-test variation at big toes reached 8.4% in diabetic patients vs. 2.2% in control subjects. Mean contralateral variation was 7.5% in diabetic patients vs. 2.5% in control subjects. Tuning-fork sensations were inversely correlated with duration of diabetes, whereas no correlation was found with HBA1c levels or the severity of retinopathy. Ninety-nine (52%) patients had vibratory sensation at big toes of

Objectif Une elevation de TSH a ete rapportee dans la population obese. Cette etude a pour objectif de determiner les liens statistiques potentiels entre la masse grasse, la leptine et le niveau de TSH. Patients et methodes Huit cents sujets consecutifs hospitalises pour un bilan d’obesite (incluant une mesure de la TSH) ont ete inclus. L’IMC et la leptinemie ont ete utilises comme reflet de l’exces d’adiposite. Une analyse statistique univariee puis multivariee a ete realisee pour identifier les parametres influencant le niveau de TSH. Resultats Nous confirmons la correlation lineaire positive entre IMC et TSH (rho = 0,085). Cette correlation est encore plus marquee entre leptine et TSH (rho = 0,146). Apres ajustement sur les facteurs de confusion dont l’IMC, la leptine reste positivement correlee a la TSH. Dans le quartile de patients avec la TSH la plus haute, l’IMC moyen est plus eleve de meme que le taux de leptine en comparaison au quartile de patients avec la TSH la plus basse. Discussion Nous rapportons chez le sujet obese un lien statistique entre le taux plasmatique de TSH et de leptine independamment de l’IMC. La litterature existante apporte des arguments en faveur d’une regulation fonctionnelle reciproque entre le tissu adipeux et l’axe thyreotrope. Le niveau de leptine qui depend a la fois de la masse de tissu adipeux et de l’etat de la balance energetique pourrait moduler la fonction thyroidienne du sujet obese pour augmenter la depense energetique et limiter la prise de poids. 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.

Objectif La transplantation d'ilots de Langerhans est une technique innovante de therapie cellulaire s'adressant aux patients diabetiques de type 1 porteur d'un diabete instable ou ayant beneficie d'une greffe de rein. Evaluer l'efficacite et la securite a 5 ans de la transplantation d'ilots de Langerhans au sein du reseau GRAGIL. Patients et methodes Etude retrospective analysant l'efficacite metabolique (HbA1c, correction des hypoglycemies, insulino-independance, dose d'insuline), la survie du greffon et la securite a 5 ans de la transplantation d'ilots de Langerhans au sein de la cohorte de patients diabetiques de type 1 transplantes dans le cadre du reseau GRAGIL entre 2003-2010. Resultats Quarante-quatre patients ont beneficie d'une transplantation d'ilots entre septembre 2003 et avril 2010. 24 patients (54,5 %) ont recu une transplantation d'ilots seule (ITA) et 20 patients (45,5 %) ont recu une transplantation d'ilots apres une greffe de rein (IAK). L'âge moyen des receveurs est de 46 ans (42-55) et l'anciennete de diabete de 33 ans (26-27). Le nombre moyen d'injection d'ilots est de 1,9 par patient. La quantite moyenne d'ilots administree est de 340 200 (279 000-427 000) IEQ/infusion, l'index de stimulation est mesure a 1,9 (1,2-2,3) et la viabilite des ilots de 92 % (81-91). Un an et 5 ans apres la transplantation d'ilots, 80 % et 65 % des receveurs atteignent une HbA1c 2 % vs seulement 9 % avant la transplantation ( p vs 18/44 (40,9 %) avant la transplantation ( p vs 0,5 (0,42-0,58) UI/kg avant la transplantation d'ilots ( p Conclusion La transplantation d'ilots est une technique efficace offrant aux receveurs une amelioration notable et durable de l'equilibre metabolique en termes de reduction de l'HbA1c et de reduction des hypoglycemies severes a long terme. 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 Le diabete 1 est une maladie bi-hormonale avec un deficit en insuline et une secretion de glucagon anormale. L'ensemble favorise l'instabilite glycemique. Dans le cadre de l'inflammation chronique des ilots, les cytokines peuvent contribuer a la perte de fonction et a l'apoptose. L'IL-1 beta est une cytokine au carrefour des voies du stress metabolique et inflammatoire. Nous avons etudie l'expression de l'IL-1beta dans les ilots de diabetiques de type 1 (DT1) Materiels et methodes L'etude a repose sur l'analyse de sections pancreatiques de DT1 ( n = 13), de sujets presentant des autoanticorps (AC + n = 6) et des sujets controles ( n = 5) provenant du consortium nPOD. L'expression de l'IL-1 beta a ete comparee simultanement par hybridation in situ et par immunfluorescence Resultats Nous avons observe que les ilots des DT1 (11/13) et les sujets AC + (5/6) contenaient plus d'ARNm de l'IL-1beta que les controles avec une importante variabilite intra et inter-sujets. En immunofluorescence, l'IL-1 beta etait retrouvee dans les cellules alpha chez 9/13 DT1 meme en l'absence de cellules beta detectables, dans les cellules alpha et beta chez 5/7 sujets AC + et dans les cellules beta de 2/5 controles. Conclusion L'expression d'IL-1 dans les cellules alpha au cours du DT1 est une donnee nouvelle dont la signification reste a preciser. 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 Le service de Diabetologie de Lyon Sud est centre initiateur dans le cadre de la mise en place du traitement ambulatoire par pompe sous cutanee a insuline en collaboration avec des prestataires. Objectifs programme PARADIS: assurer le telesuivi et la teleassistance des patients sous pompe. Creation d’un lien informatique entre professionnels de sante et patients a domicile. Il permet d’optimiser l’education et la semaine d’initiation au nouveau traitement. But: mieux comprendre et repondre a leurs besoins et problemes, evaluer l’opportunite de la poursuite du traitement. Il favorise l’interface patients/ medecins/paramedicaux/prestataires. Patients et methodes Groupe de travail initie depuis 1 an pour la creation du logiciel avec le chef de service, le cadre, infirmiere d’education et les membres de la DSII: dossier educatif, parcours tele suivi, module teleassistance. Creation d’un livret d’education destine au patient remis a l’initiation: outil reprenant les conduites a tenir, son quotidien sous pompe, renforcant l’education. Il sera integre au logiciel PARADIS afin d’etre consultable informatiquement. Mise en place d’un groupe de patients tests afin de mieux s’adapter a leurs attentes et de reajuster les items du logiciel. Inclusion de tous nos patients traites par pompe lors de l’initiation, consultation ou hospitalisation. Resultats Mise en œuvre de l’interface a domicile: novembre 2014. Poursuite de la participation du groupe test. Resultats statistiques et realisation de tableaux de bord: – nombre de patients sous pompe, par prestataire, type de pompe, de catheter – analyse HbA1c: evolution – analyse des problemes rencontres a domicile. Amelioration du suivi du patient: – rendez-vous – renouvellement ordonnances – evaluation qualite de vie, connaissances. Conclusion L’interface informatique vient de se mettre en place, necessitant formation du personnel. Evaluation prevue a 3 mois aupres des equipes et patients a partir d’un questionnaire. Resultats statistiques a analyser. Presentation des differentes fonctionnalites du logiciel. 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.

As clinicians, we are faced to difficult situations in young diabetic patients. The prevalence of type 2 diabetes increases in these patients due to a rising incidence of obesity. We present two clinical observations which both illustrate the insufficiencies of the present classifications. Modern tools are now available for diagnosis such as anti-GAD65 and IA-2 antibodies, genetic tools to investigate for specific mutations, but quantitative means of beta cell mass are lacking. Clinical examination is still accurate to identify type 1 or type 2 diabetes, MODY and mitochondrial diabetes. Weight curve, lesions of acanthosis nigricans, criteria of metabolic syndrome, history of diabetes are critical factors. This problematic has important consequences in our daily practice: the right choice for rapid and good metabolic control.