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The glucagon-like peptide 1 receptor (GLP1R) is a major drug target with several agonists being prescribed in patients with type 2 diabetes (T2D) and obesity. The impact of genetic variability of the GLP1R gene on receptor function and its association with metabolic traits are unclear. Here, functional profiling of 59 rare and one common GLP1R variant across four signaling pathways reveals an unexpected diversity of phenotypes ranging from defective cell surface expression to complete or pathway-specific gain- and loss-of-functions. Defective insulin secretion of loss-of-function GLP1R variants was rescued by allosteric GLP1R ligands or high exendin-4 concentrations in INS-1 823/3 cells. Genetic association studies in 200K participants from UK Biobank show that impaired GLP1R cell surface expression contributes to impaired glucose control and increased adiposity with increased HbA1c, BMI and diastolic blood pressure. This study defines impaired GLP-1R cell surface expression as a risk factor for T2D- and obesity-associated traits.

International audience; Objective: To investigate the efficacy of the Diabeloop Generation-1 (DBLG1) closed-loop system to control the hypoglycaemia induced by physical activity (PA) in real-life conditions.Methods: This was a post-hoc analysis of the Diabeloop WP7 multicentre randomized controlled trial. Glycaemic outcomes were compared between days with and without PA in 56 patients with type 1 diabetes (T1D) using DBLG1 for 12 weeks. After the patient announces a PA, DBLG1 reduces insulin delivery and, if necessary, calculates the amount of preventive carbohydrates (CHO).Results: Daily time spent in the interstitial glucose range

International audience; Genome-wide association studies have identified 240 independent loci associated with type 2 diabetes (T2D) risk, but this knowledge has not advanced precision medicine. In contrast, the genetic diagnosis of monogenic forms of diabetes (including maturity-onset diabetes of the young (MODY)) are textbook cases of genomic medicine. Recent studies trying to bridge the gap between monogenic diabetes and T2D have been inconclusive. Here, we show a significant burden of pathogenic variants in genes linked with monogenic diabetes among people with common T2D, particularly in actionable MODY genes, thus implying that there should be a substantial change in care for carriers with T2D. We show that, among 74,629 individuals, this burden is probably driven by the pathogenic variants found in GCK, and to a lesser extent in HNF4A, KCNJ11, HNF1B and ABCC8. The carriers with T2D are leaner, which evidences a functional metabolic effect of these mutations. Pathogenic variants in actionable MODY genes are more frequent than was previously expected in common T2D. These results open avenues for future interventions assessing the clinical interest of these pathogenic mutations in precision medicine.

Objective: There is room for improvement in the performance of closed-loop regulation algorithms during the prandial period. This in silico study evaluated the efficiency and safety of ultrarapid lispro insulin using the Diabeloop DBLG1® algorithm. Methods: We modeled the insulin profile of URLi according to literature data and integrated it to the model used within a simulation platform built from a 60 patients’ virtual cohort. We then ran the DBLG1® algorithm in silico with various meal intakes using modeled URLi, Aspart and Faster Aspart. The primary endpoints were glucose metrics (time in 70-180 mg/dL range and time below range). Results: When insulin time constant values were tuned, time in 70-180 mg/dL range was 69.4 [61.1-75.6] (Aspart) vs 74.7 [65.5-81.5] (URLi). Glucose coefficient of variation was reduced from 34.1 [29.7-37.8] to 28.4 [25.7-34.6]. Time below 70 mg/dL and 54 mg/dL were significantly reduced with URLi, whether or not DBLG1 was specifically tuned to this insulin. Metrics with Faster Aspart were intermediate and did not significantly differ from URLi. Conclusions: This simulation study performed on a virtual T1D population suggests that the use of URLi within an unmodified closed-loop DBLG1 regulation algorithm is safe and, with DBLG1 being tuned to this specific insulin type, improved the regulation performances as compared with Aspart. This fact supports the use of such an insulin in clinical investigations.

Background: Automated insulin delivery is an efficient treatment for patients with type 1 diabetes. Little is known on its impact on patients with excessive time in hypoglycaemia. Methods: We performed a post hoc analysis of three randomized control trials that used the DBLG1 (Diabeloop Generation 1) hybrid closed-loop solution. Patients whose time below 70 mg/dL during baseline, open-loop phase exceeded 5% were selected. The outcomes were the differences between the closed-loop and the open-loop phases in time in various ranges and Glycemia Risk Index (GRI). Results: We identified 45 patients exhibiting ≥5% of time below 70 mg/dL during the open-loop phase. Under closed-loop, the time in hypoglycaemia (54 to −4). The time below 54 mg/dL decreased from 1.9% (SD 1.3) to 0.8% (SD 0.7) (difference −0.9% [−1.4; –0.8], P < 10−4). The time in range (TIR 70-180 mg/dL) improved from 63.3 (SD 9.5) to 68.2% (SD 8.2) (difference 5.1% [2.9; 7.0], P < 10−4). The GRI improved from 51.2 (SD 12.4) to 38.0 (SD 10.9) (difference 13.2 [10.4; 16.0], P < 10−4). Conclusion: DBLG1 decreased time in hypoglycaemia by more than 50% even in patients with excessive time in hypoglycaemia at baseline, while also improving both TIR and GRI, under real-life conditions. The improvement in GRI (13.2%) exceeded that of the improvement in TIR (5.1%) indicating that in this data set, GRI was more sensitive than TIR to the improvement in glycaemia achieved with closed-loop. These results support the safety and efficacy of this treatment.

Introduction: The DBLG1 Hybrid Closed-Loop system improves time in range and glycemic control in adults. However, the efficacy and safety of the system had not yet been evaluated in children. Objective: of this study is to evaluate the non-inferiority of the DBL4K (Diabeloop for Kids) hybrid closed-loop system (Kaleido pump + Dexcom G6 = CL) compared to a Dexcom G6 sensor augmented pump (open loop = OL) in prepubescent children. Materials and Methods: Multicenter open-label randomized controlled trial in 3 pediatric diabetology centers, 2 of which are French. The CL and OL are allocated for 4 days in hospital, followed by 6 weeks at home for the French centers. Results: Seventeen patients (mean age: 8.3+/- 1.6 years) were included for evaluation at 6 weeks at home between March and December 2019. The percentage of time spent in range (0.7-1.8 g/L) was significantly higher in the CL group during the 6 weeks at home (66.19% in CL vs. 58.68% in OL, p Conclusions: The DBL4K Closed-Loop System is suitable for prepubescent children. It is not inferior to sensor augmented pump therapy in children. Just as in adults it improves the time in range while decreasing the time spent in hypoglycemia. It could allow for better long-term glucose control in children with diabetes. Disclosure D. Kariyawasam: None. C. Morin: None. K. Casteels: None. C. Le Tallec: None. C. Godot: None. A. Sfez: None. N. Garrec: None. M. Polak: Other Relationship; Self; AMMTeK. G. Charpentier: Other Relationship; Self; Diabeloop. S. Franc: Advisory Panel; Self; Diabeloop SA. Board Member; Self; Novo Nordisk. Research Support; Self; Merck Sharp & Dohme Corp. Stock/Shareholder; Self; Diabeloop SA. Other Relationship; Self; Abbott Diabetes. J. Beltrand: None.

The aim of this study is to assess the effect of meal size on glycemic control for T1D patients equipped with Diabeloop’s DBLG1 Closed Loop System[1], based on data from DBLG1 System Commercial Launch. The Soft Launch dataset comprises 34 adult type 1 diabetes patients with an average duration of 206 days for a total of 7011 days of treatment. Only days with ≥70% available CGM data were included in the analysis (97.3 % of total). To assess the effect of patient meal size (the daily sum of CHO declared by each patient on his device) on glycemic control, we compute the difference in percentage point between patient daily value and patient daily mean value of both Time In Range (TIR) (Figure 1) and Time In Hyperglycemia (TIHYPER) and plot it against each daily CarboHydrates (CHO) as a percentage of the mean daily CHO for this patient. This way we can observe the effect of bigger and smaller than average meals and determine if they tend to increase or decrease TIR and TIHYPER. As presented on Figure 1, days with increased CHO consumption are not linked to a drop in TIR. We observe no correlation between the TIR and the daily amount of CHO ingested (r=0.01), nor between the TIHYPER and the daily amount of CHO ingested (r=-0.12). In conclusion, Diabeloop’s DBLG1 Closed Loop System’s performance is not altered by the variations in daily amount of carbohydrates ingested by T1D patients. Disclosure P. Gimenez: Employee; Self; Diabeloop SA. S. Lachal: Employee; Self; Diabeloop SA. Y. Tourki: Employee; Self; Diabeloop SA. S. Franc: Advisory Panel; Self; Diabeloop SA, Board Member; Self; Novo Nordisk, Other Relationship; Self; Abbott Diabetes, Research Support; Self; Merck Sharp & Dohme Corp., Stock/Shareholder; Self; Diabeloop SA. C. Amadou: Other Relationship; Self; AstraZeneca, Diabeloop SA, Lilly Diabetes. A. Penfornis: Board Member; Self; Medtrum Technologies, Merck Sharp & Dohme Corp., Mundipharma International, Sanofi-Aventis, Other Relationship; Self; Medtrum Technologies, Speaker’s Bureau; Self; Amgen Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi-Aventis. G. Charpentier: Other Relationship; Self; Diabeloop. P. Y. Benhamou: Consultant; Self; Diabeloop SA, Eli Lilly and Company, Insulet Corporation, Other Relationship; Self; Abbott Diabetes.

This study aims to assess the interoperability of Diabeloop’s DBLG1 Closed Loop System on glycemic control for T1D patients, based on data from clinical trials NCT02987556[1] (SP7) and NCT04190277 (SP8). SP7 study was conducted on 63 out of 68 patients randomly assigned to two arms equipped with DBLG1 system using Cellnovo pump for arm 1 and Kaleido pump for arm 2. All patients attended a 12-week open loop (OL) phase (receiving their usual treatment) and a 12-week closed loop (CL) phase (using DBLG1 system). In SP8 study, 178 out of 184 patients, randomly assigned to two arms, started with a 2-week baseline phase in OL. The next 12 weeks, patients in arm 2 remained in OL while patients in arm 1 switched to CL equipped with DBLG1 System using DANA Diabecare-i insulin pump. The study was shortened due to COVID-19 epidemic. To assess the improvement reached by DBLG1 System, we compared the average time in range 70-180 mg/dL (TIR) between OL and active CL phases. For SP7 study, we analysed data from both arms. For SP8 study, to assess the TIRs for the same patients, we compared baseline and CL phases for arm 1. As shown in Figure 1, for SP7 the average TIRs increased by 8.6% for arm 1 (32 patients) and by 14.0% for arm 2 (31 patients in CL, 30 in OL). For SP8 arm 1 the average TIR increased by 12.8% (142 patients). DBLG1 System improved the TIR despite the use of 3 different pumps. Therefore, improvement linked with DBLG1 System on the average TIR is independent of the pump used. Disclosure A. Adenis: Employee; Self; Diabeloop SA. L. Pou: Employee; Self; Diabeloop SA. H. M. Romero-ugalde: Employee; Self; Diabeloop SA. Y. Tourki: Employee; Self; Diabeloop SA. S. Franc: Advisory Panel; Self; Diabeloop SA, Board Member; Self; Novo Nordisk, Other Relationship; Self; Abbott Diabetes, Research Support; Self; Merck Sharp & Dohme Corp., Stock/Shareholder; Self; Diabeloop SA. G. Charpentier: Other Relationship; Self; Diabeloop. P. Y. Benhamou: Consultant; Self; Diabeloop SA, Eli Lilly and Company, Insulet Corporation, Other Relationship; Self; Abbott Diabetes. M. Doron: Research Support; Self; Diabeloop SA. E. Huneker: Employee; Self; Diabeloop SA.

Aims To compare closed-loop (CL) and open-loop (OL) systems for glycaemic control in patients with type 1 diabetes (T1D) exposed to real-life challenging situations (gastronomic dinners or sustained physical exercise). Methods Thirty-eight adult patients with T1D were included in a three-armed randomized pilot trial (Diabeloop WP6.2 trial) comparing glucose control using a CL system with use of an OL device during two crossover 72-hour periods in one of the three following situations: large (gastronomic) dinners; sustained and repeated bouts of physical exercise (with uncontrolled food intake); or control (rest conditions). Outcomes included time in spent in the glucose ranges of 4.4-7.8 mmol/L and 3.9-10.0 mmol/L, and time in hypo- and hyperglycaemia. Results Time spent overnight in the tight range of 4.4 to 7.8 mmol/L was longer with CL (mean values: 63.2% vs 40.9% with OL; P ≤ .0001). Time spent during the day in the range of 3.9 to 10.0 mmol/L was also longer with CL (79.4% vs 64.1% with OL; P ≤ .0001). Participants using the CL system spent less time during the day with hyperglycaemic excursions (glucose >10.0 mmol/L) compared to those using an OL system (17.9% vs 31.9%; P ≤ .0001), and the proportions of time spent during the day with hyperglycaemic excursions of those using the CL system in the gastronomic dinner and physical exercise subgroups were of similar magnitude to those in the control subgroup (18.1 ± 6.3%, 17.2 ± 8.1% and 18.4 ± 12.5%, respectively). Finally, times spent in hypoglycaemia were short and not significantly different among the groups. Conclusions The Diabeloop CL system is superior to OL devices in reducing hyperglycaemic excursions in patients with T1D exposed to gastronomic dinners, or exposed to physical exercise followed by uncontrolled food and carbohydrate intake.

TeleDiab‐2 was a 13‐month randomized controlled trial evaluating the efficacy and safety of two telemonitoring systems to optimize basal insulin (BI) initiation in subjects with inadequately controlled type 2 diabetes (HbA1c, 7.5%‐10%). A total of 191 participants (mean age 58.7 years, mean HbA1c 8.9%) were randomized into three groups: group 1(G1, standard care, n = 63), group 2 (G2, interactive voice response system, n = 64) and group 3 (G3, Diabeo‐BI app software, n = 64). The two telemonitoring systems proposed daily adjustments of BI doses, in order to facilitate the achievement of fasting blood glucose (FBG) values targeted at ~100 mg/dL. At 4 months follow‐up, HbA1c reduction was significantly higher in the telemonitoring groups (G2: −1.44% and G3: −1.48% vs. G1: −0.92%; P

Summary: Background: Closed-loop insulin delivery systems are expected to become a standard treatment for patients with type 1 diabetes. We aimed to assess whether the Diabeloop Generation 1 (DBLG1) hybrid closed-loop artificial pancreas system improved glucose control compared with sensor-assisted pump therapy. Methods: In this multicentre, open-label, randomised, crossover trial, we recruited adults (aged ≥18 years) with at least a 2 year history of type 1 diabetes, who had been treated with external insulin pump therapy for at least 6 months, had glycated haemoglobin (HbA1c) of 10% or less (86 mmol/mol), and preserved hypoglycaemia awareness. After a 2-week run-in period, patients were randomly assigned (1:1) with a web-based system in randomly permuted blocks of two, to receive insulin via the hybrid closed-loop system (DBLG1; using a machine-learning-based algorithm) or sensor-assisted pump therapy over 12 weeks of free living, followed by an 8-week washout period and then the other intervention for 12 weeks. The primary outcome was the proportion of time that the sensor glucose concentration was within the target range (3·9–10·0 mmol/L) during the 12 week study period. Efficacy analyses were done in the modified intention-to-treat population, which included all randomly assigned patients who completed both 12 week treatment periods. Safety analyses were done in all patients who were exposed to either of the two treatments at least once during the study. This trial is registered with ClinicalTrials.gov, number NCT02987556. Findings: Between March 3, 2017, and June 19, 2017, 71 patients were screened, and 68 eligible patients were randomly assigned to the DBLG1 group (n=33) or the sensor-assisted pump therapy group (n=35), of whom five dropped out in the washout period (n=1 pregnancy; n=4 withdrew consent). 63 patients completed both 12 week treatment periods and were included in the modified intention-to-treat analysis. The proportion of time that the glucose concentration was within the target range was significantly higher in the DBLG1 group (68·5% [SD 9·4] than the sensor-assisted pump group (59·4% [10·2]; mean difference 9·2% [95% CI 6·4 to 11·9]; p

Benefits of telemedicine have been proven in the field of diabetes. Among a number of technical solutions, Diabeo® has been studied in both type 1 and type 2 diabetes with intensive insulin therapy. This digital therapeutic system contains a self-monitoring glucose logbook and offers automated insulin dose recommendations thanks to a fully customizable algorithm. In addition, the cloud-based dedicated software also has features to facilitate remote monitoring, including a platform for diabetes nurses who perform coaching and treatment adjustment. A detailed description of this telemedicine system is provided, as well as results of completed clinical studies. In particular, TeleDiab 1’s positive results on HbA1c in type 1 diabetes are detailed. We conclude with a discussion of the role of this telemedicine system within the landscape of mobile apps for diabetes.

Diabetes & Metabolism - Sous presse. Manuscrit accepte. Disponible en ligne depuis le samedi 16 octobre 2021

OBJECTIVE The ACE insertion/deletion (I/D) polymorphism has been widely studied in people with diabetes, albeit not with regard to lower-limb amputation (LLA). We examined associations among this polymorphism, plasma ACE concentration, and LLA in people with type 1 diabetes. RESEARCH DESIGN AND METHODS ACE I/D genotype and plasma ACE were assessed in three prospective cohorts of participants with type 1 diabetes. LLA was defined as minor (below-the-ankle amputation consisting of at least one ray metatarsal resection) or major (transtibial or transfemoral) amputation. Linear, logistic, and Cox regression models were computed to evaluate the likelihood of prevalent and incident LLA by ACE genotype (XD [ID or ID] vs. II) and plasma ACE, after adjusting for confounders. RESULTS Among 1,301 participants (male 54%, age 41 ± 13 years), 90 (6.9%) had a baseline history of LLA. Baseline LLA was more prevalent in XD (7.4%) than in II genotype (4.5%, odds ratio [OR] 2.17 [95 %CI 1.03–4.60]). Incident LLA occurred in 53 individuals during the 14-year follow-up and was higher in XD versus II carriers (hazard ratio 3.26 [95% CI 1.16–13.67]). This association was driven by excess risk of minor, but not major, LLA. The D allele was associated with increased prevalent LLA at the end of follow-up (OR 2.48 [1.33–4.65]). LLA was associated with higher mean (95% CI) ACE levels in II (449 [360, 539] vs. 354 [286, 423] ng/mL), but not XD (512 [454, 570] vs. 537 [488, 586]), carriers. CONCLUSIONS This report is the first of an independent association between ACE D allele and excess LLA risk, mainly minor amputations, in patients with type 1 diabetes.

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.

OBJECTIVE To analyze safety and efficacy of the DBLG1 hybrid closed-loop artificial pancreas system in patients with Type 1 Diabetes in real life conditions. METHODS Following a one-week run-in period with usual pump, 25 patients were provided with the commercial DBLG1 system. We present the results of Time-in-Range and HbA1c over a 6-month period. RESULTS The mean (SD;range) age of patients was 43 years (13.8; 25-72). At baseline, mean HbA1c and TIR 70-180mg/dL were respectively 7.9% (0.93; 5.6- 8.5) [63mmol/mol (10; 38-69)] and 53% (16.4;21-85). One patient stopped using the system after 2 months. At 6-month, mean HbA1c decreased to 7.1% [54mmol/mol] (p CONCLUSION The DBLG1 System confirms its ability to significantly improve glycemic control in real life conditions, without serious adverse events.

International audience; Melatonin is a hormone mainly produced by the pineal gland and MT1 is one of the two G protein-coupled receptors (GPCRs) mediating its action. Despite an increasing number of available GPCR crystal structures, the molecular mechanism of activation of a large number of receptors, including MT1, remains poorly understood. The purpose of this study is to elucidate the structural elements involved in the process of MT1’s activation using naturally occurring variants affecting its function. Thirty-six nonsynonymous variants, including 34 rare ones, were identified in MTNR1A (encoding MT1) from a cohort of 8687 individuals and their signaling profiles were characterized using Bioluminescence Resonance Energy Transfer-based sensors probing 11 different signaling pathways. Computational analysis of the experimental data allowed us to group the variants in clusters according to their signaling profiles and to analyze the position of each variant in the context of the three-dimensional structure of MT1 to link functional selectivity to structure. MT1 variant signaling profiles revealed three clusters characterized by (1) wild-type-like variants, (2) variants with selective defect of βarrestin-2 recruitment, and (3) severely defective variants on all pathways. Our structural analysis allows us to identify important regions for βarrestin-2 recruitment as well as for Gα12 and Gα15 activation. In addition to identifying MT1 domains differentially controlling the activation of the various signaling effectors, this study illustrates how natural variants can be used as tools to study the molecular mechanisms of receptor activation.

Medico-economic data of patients suffering from chronic nausea and vomiting are lacking. In these patients, gastric electrical stimulation (GES) is an effective, but costly treatment. The aim of this study was to assess the efficacy, safety and medico-economic impact of Enterra therapy in patients with chronic medically refractory nausea and vomiting.Data were collected prospectively from patients with medically refractory nausea and/or vomiting, implanted with an Enterra device and followed for two years. Gastrointestinal quality of life index (GIQLI) score, vomiting frequency, nutritional status and safety were evaluated. Direct and indirect expenditure data were prospectively collected in diaries.Complete clinical data were available for142 patients (60 diabetic, 82 non-diabetic) and medico-economic data were available for 96 patients (36 diabetic, 60 non-diabetic), 24 months after implantation. GIQLI score increased by 12.1 ± 25.0 points (p.001), with a more significant improvement in non-diabetic than in diabetic patients (+15.8 ± 25.0 points, p.001 versus 7.3 ± 24.5 points, p = .027, respectively). The proportion of patients vomiting less than once per month increased by 25.5% (p.001). Hospitalisations, time off work and transport were the main sources of costs. Enterra therapy decreased mean overall healthcare costs from 8873 US$ to 5525 US$ /patient/year (p = .001), representing a saving of 3348 US$ per patient and per year. Savings were greater for diabetic patients (4096 US$ /patient/year) than for non-diabetic patients (2900 US$ /patient/year).Enterra therapy is an effective, safe and cost-effective option for patients with refractory nausea and vomiting.gov Identifier: NCT00903799.

AIM To compare the efficacy of the closed-loop Diabeloop for highly unstable diabetes (DBLHU) system with the open-loop predictive low glucose suspend (PLGS) system in patients with highly unstable type 1 diabetes (T1D) who experience acute metabolic events. METHODS DBLHU-WP10 was an interventional, controlled, randomized, open-label study that comprised two cycles of N-of-1 trials (2-of-1 trials). Each trial consisted of two crossover 4-week periods of treatment with either DBLHU or PLGS in randomized order. The primary outcome was the percentage of time spent in the 70-180 mg/dL glucose range (time in range [TIR]). RESULTS Five out of seven randomized patients completed the aggregated 2-of-1 trials. TIR was significantly higher with DBLHU (73.3% ± 1.7%) compared with PLGS (43.5% ± 1.7%; P

The daily challenge for people with type 1 diabetes is maintaining glycaemia in the "normal" range after meals, by injecting themselves the correct amount of insulin. Artificial pancreas systems were developed to adjust insulin delivery based on real-time monitoring of glycaemia and meal patient's report. Meal reporting is a heavy burden for patients as it requires carbohydrate estimation several times per day. To improve patient's quality of life and treatment, several methods aim at detecting unannounced meals. While untreated meals lead to hyperglycaemia and in the long-term to comorbidities, treating falsely detected meals can cause hypoglycaemia and coma. In this paper, we propose to customise the meal detection to the patient's hourly meal probability in order to limit false detection of unannounced meals.

Objective: Previous trials demonstrated an improvement of glycemic control with the single hormone closed-loop system Diabeloop DBLG1. Therefore, efficacy assessment of this system in real life situation is eagerly awaited. A preliminary analysis of glucose TIR (time-in-range) after a mean of 20 weeks of follow-up was previously communicated. The aim of this report is to present results of TIR and HbA1c after 6-month of follow-up. Methods: After a run-in period with G6 sensor and usual pump, 25 patients with T1D in Corbeil-Essonne and Grenoble diabetes centers (France) were provided with the commercial setting of DBLG1 System (G6 sensor and Kaleido pump). They were taught to manage it during a one to five days hospitalization. Data on system parameters and glycemic control were collected from a cloud platform. We present here the results of TIR and HbA1c after 6 months of follow-up. Results: Mean age of patients was 43 years (25-72) with a mean duration of diabetes of 19 years (2-43). All patients were already insulin pump users and 76% of patients were women. The run-in period lasted an average of 7 days (4-15). The mean HbA1c and TIR 70-180 mg/dL before DBLG1 System initiation were respectively 7.9% (5.6 to 8.5 %) [63mmol/mol, 38 to 69 mmol/mol] and 53% (21 to 85%). One patient decided to stop using the system after 2 months due to repeated system disconnections and was therefore excluded from the 6-months analysis. After a mean follow-up of 6 months, mean HbA1c decreased from 7.9% to 7.1% [63 to 54 mmol/mol] (p< 0.001*) and TIR 70-180 mg/dL increased from a mean of 53 to 67% (p Disclosure C. Amadou: None. S. Franc: Consultant; Self; Diabeloop SA. P.Y. Benhamou: Consultant; Self; Abbott, Diabeloop SA, Eli Lilly and Company, Insulet Corporation, Novo Nordisk Inc., Sanofi. S. Lablanche: None. E. Huneker: Stock/Shareholder; Self; Diabeloop SA. G. Charpentier: Board Member; Self; Diabeloop SA. A. Penfornis: None.

Background: The DIABEO® system (DS) is a telemedicine solution that combines a mobile app for patients with a web portal for health care providers. DS allows real-time monitoring of basal-bolus insulin therapy as well as therapeutic decision-making, integrating both basal and bolus dose calculation. Real-life studies have shown a very low rate of use of mobile health applications by patients. Therefore, we conducted a large randomized controlled trial study to investigate the efficacy of DS in conditions close to real life (TELESAGE study). Methods: TELESAGE was a multicenter, randomized, open study with three parallel arms: arm 1 (standard care), arm 2 (DIABEO alone), and arm 3 (DIABEO+telemonitoring by trained nurses). The primary outcome assessed the reduction in HbA1c levels after a 12-month follow-up. Results: Six hundred sixty-five patients were included in the study. Participants who used DIABEO once or more times a day (DIABEO users) showed a significant and meaningful reduction of HbA1c versus standard care after a 12-month follow-up: mean difference −0.41% for arm 2—arm 1 (P = 0.001) and −0.51% for arm 3—arm 1 (P ≤ 0.001). DIABEO users included 25.1% of participants in arm 2 and 37.6% in arm 3. In the intention-to-treat population, HbA1c changes and incidence of hypoglycemia were comparable between arms. Conclusions: A clinical and statistically significant reduction in HbA1c levels was found in those patients who used DIABEO at least once a day.

Purpose The aim of this study is to demonstrate that the total number of days in hospital required for healing of a de novo diabetes-related foot ulcer (DFU) is lower in patients followed up using a telemedicine platform (Télépied Follow-Up group [Group 2]) than in patients followed up using standard care (Standard Follow-Up control group [Group 1]). Patients are assigned to either Group 1 or Group 2 depending on whether their first inclusion visit is during an even or odd week. Patients included in Group 1 are to be followed at spaced intervals during day hospital visits by the investigator assisted by a specialized referral nurse as part of the regular follow-up procedure (dressing changes + ulcer monitoring). Between visits, an independent nurse (IN) provides local care on a daily basis. Patients included in Group 2 have their DFU treated by a referral nurse trained at the diabetic foot unit of the investigating centre, and they are also followed up by an IN under the supervision of a referral nurse. In Group 2, monitoring of lesions is performed weekly by the referral nurse using photos of the DFU with planimetry taken by the IN and sent to the referral nurse via telemedicine software. The referral nurse can, in turn, provide guidance to the IN on the care to be provided and/or decide that a further hospital visit is needed. Both treatment groups are to be followed for 12 months or until complete healing of the ulcer. Results Recruitment for the study began in March 2017 and ended in May 2019, with the final study visit scheduled for May 2020. Conclusion The aim of the Télépied study is to assess the impact of ambulatory foot ulcer management in diabetics over a 1-year period by a non-specialized IN working under the supervision of a referral nurse via telemedicine follow-up versus standard follow-up by an IN alone. The primary endpoint is the total duration of hospitalization required until full healing of the ulcer.

There have been conflicting results from trials of gastric electrical stimulation (GES) for treatment of refractory vomiting, associated or not with gastroparesis. We performed a large, multicenter, randomized, double-blind trial with crossover to study the efficacy of GES in patients with refractory vomiting, with or without gastroparesis.For 4 months, we assessed symptoms in 172 patients (66% women; mean age ± standard deviation, 45 ± 12 years; 133 with gastroparesis) with chronic (12 months) of refractory vomiting (idiopathic, associated with a type 1 or 2 diabetes, or postsurgical). A GES device was implanted and left unactivated until patients were randomly assigned, in a double-blind manner, to groups that received 4 months of stimulation parameters (14 Hz, 5 mA, pulses of 330 μs) or no stimulation (control); 149 patients then crossed over to the other group for 4 months. Patients were examined at the end of each 4-month period (at 5 and 9 months after implantation). Primary endpoints were vomiting score, ranging from 0 (daily vomiting) to 4 (no vomiting), and the quality of life, assessed by the Gastrointestinal Quality of Life Index scoring system. Secondary endpoints were changes in other digestive symptoms, nutritional status, gastric emptying, and control of diabetes.During both phases of the crossover study, vomiting scores were higher in the group with the device on (median score, 2) than the control group (median score, 1; P.001), in diabetic and nondiabetic patients. Vomiting scores increased significantly when the device was ON in patients with delayed (P.01) or normal gastric emptying (P = .05). Gastric emptying was not accelerated during the ON period compared with the OFF period. Having the GES turned on was not associated with increased quality of life.In a randomized crossover study, we found that GES reduced the frequency of refractory vomiting in patients with and without diabetes, although it did not accelerate gastric emptying or increase of quality of life. Clinicaltrials.gov, Number: NCT00903799.

Therapeutic inertia is a substantial obstacle to the initiation of insulin therapy in people with uncontrolled type 2 diabetes (T2D). This effect has in part been perpetuated by concerns over the impact of a burdensome regimen and the increased risk of hypoglycemia and body weight gain often associated with insulin use. An effective, yet simple, less burdensome regimen with a lower risk of body weight gain and hypoglycemia compared with an insulin-only regimen, may help to address these concerns more effectively. We review the available clinical and real-world data on IDegLira, a once-daily, injectable, fixed-ratio combination of insulin degludec (degludec) and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide, in people with T2D. Evidence from the comprehensive DUAL clinical trial program suggests an advantage of IDegLira over traditional insulin therapies in a number of clinical outcomes, including maintenance of glycemic control, achievement of glycemic targets, reducing the risk of hypoglycemia, and body weight loss. These findings were demonstrated in participants with T2D irrespective of prior GLP-1RA and insulin use. Furthermore, the individual components of IDegLira have confirmed safety (degludec) or significant benefit in terms of improvement of cardiovascular risk (liraglutide). As an injectable therapy that is simple to titrate, IDegLira has the potential to optimize the ability to achieve relevant glycemic targets, and offers a suitable treatment option for people with T2D requiring insulin therapy who are at risk of hypoglycemia or weight gain.