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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.

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.

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.

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.

Aims: To assess the effect of baseline body mass index (BMI) and the occurrence of nausea and/or vomiting on weight loss induced by semalgutide, a once-weekly glucagon-like peptide 1 analogue for the treatment of type 2 diabetes. Semaglutide demonstrated superior reductions in HbA1c and superior weight loss (by 2.3-6.3 kg) versus different comparators across the SUSTAIN 1 to 5 trials; the contributing factors to weight loss are not established. Materials and Methods: Subjects with inadequately controlled type 2 diabetes (drug-naive or on background treatment) were randomized to subcutaneous semaglutide 0.5 mg (excluding SUSTAIN 3), 1.0 mg (all trials), or comparator (placebo, sitagliptin, exenatide extended release or insulin glargine). Subjects were subdivided by baseline BMI and reporting (yes/no) of any nausea and/or vomiting. Change from baseline in body weight was assessed within each trial and subgroup. A mediation analysis separated weight loss into direct or indirect (mediated by nausea or vomiting) effects. Results: Clinically relevant weight-loss differences were observed across all BMI subgroups, with a trend towards higher absolute weight loss with higher baseline BMI. Overall, 15.2% to 24.0% and 21.5% to 27.2% of subjects experienced nausea or vomiting with semaglutide 0.5 and 1.0 mg, respectively, versus 6.0% to 14.1% with comparators. Only 0.07 to 0.5 kg of the treatment difference between semaglutide and comparators was mediated by nausea or vomiting (indirect effects). Conclusions: In SUSTAIN 1 to 5, semaglutide-induced weight loss was consistently greater versus comparators, regardless of baseline BMI. The contribution of nausea or vomiting to this weight loss was minor. (Less)

International audience; The G-protein-coupled receptor accessory protein MRAP2 is implicated in energy control in rodents, notably via the melanocortin-4 receptor1. Although some MRAP2 mutations have been described in people with obesity1-3, their functional consequences on adiposity remain elusive. Using large-scale sequencing of MRAP2 in 9,418 people, we identified 23 rare heterozygous variants associated with increased obesity risk in both adults and children. Functional assessment of each variant shows that loss-of-function MRAP2 variants are pathogenic for monogenic hyperphagic obesity, hyperglycemia and hypertension. This contrasts with other monogenic forms of obesity characterized by excessive hunger, including melanocortin-4 receptor deficiency, that present with low blood pressure and normal glucose tolerance4. The pleiotropic metabolic effect of loss-of-function mutations in MRAP2 might be due to the failure of different MRAP2-regulated G-protein-coupled receptors in various tissues including pancreatic islets.

Type 1 Diabetes is an autoimmune disease that eliminates endogenous insulin production. Without the crucial hormone insulin, which is necessary to equilibrate the blood glucose level, the patient must inject insulin subcutaneously. Treatment must be personalized (timing and size of insulin delivery) to achieve glycaemic equilibrium and avoid long-term comorbidities. Patients are educated on Functional Insulin Therapy (FIT) in order to independently adjust insulin delivery several times a day (at least prior to each meal and physical activity). Among personalized parameters, the Correction Factor is used to occasionally correct hyperglycemia via the injection of an insulin dose (bolus) and its value determines the bolus size. Although well-known in common diabetes practice for chronically poorly controlled patients, the phenomenon of "hyperglycemia induces insulin resistance" on a short term basis in patients with rather well controlled diabetes is presented here. Using a new database of evidence, we show that the insulin sensitivity factor, depends on the current level of glycaemia. This opens the door to refining dosing rules for patients and insulin delivery devices in artificial pancreas systems.

Background: The efficacy/safety of device-supported versus routine titration with Gla-300 in type 2 diabetes (T2DM) was evaluated. Method: AUTOMATIX was a 16-week, randomized, open-label, parallel-group, multicenter, noninferiority trial in insulin-treated or insulin-naïve people with T2DM. The fasting self-monitored plasma glucose (FSMPG) target was 90-130 mg/dL (5.0-7.2 mmol/L). Primary endpoint: proportion of participants achieving target FSMPG at week 16 without severe hypoglycemia. Secondary endpoints included: proportion reaching FSMPG target without confirmed (≤70 mg/dL [≤3.9 mmol/L]) or severe hypoglycemia; time to first achieve FSMPG target; mean FSMPG and HbA1c change (baseline to week 16). Safety endpoints included hypoglycemia and adverse events. Patient-reported outcomes (PROs) were also assessed. Results: Participants were randomized to device-supported (n = 75) or routine titration (n = 76); 17 participants in the device-supported group discontinued device use. Noninferiority was achieved for the primary endpoint (device-supported: 45.9%, routine: 36.8%; weighted difference: 9.04 [95% CI: −6.75, 24.83]), but not superiority ( P = .262). The proportion reaching FSMPG target range without confirmed (≤70 mg/dL [≤3.9 mmol/L]) or severe hypoglycemia was 34.3% vs 14.5%, respectively. The time at which 50% of the participants achieved the FSMPG target was less in the device-supported than routine titration arm (10 vs 13 weeks). Least squares mean HbA1c reduction, safety profiles, and PROs were similar in both arms. Mean “ease of use” score for the device, assessed by healthcare professionals and participants on a scale of 1-7, was ≥6. Conclusions: Device-supported self-titration had a good safety/efficacy profile, and was noninferior to routine titration and well accepted by diabetes specialists and patients.

This paper presents the first autoregressive with exogenous input (ARX) model using energy expenditure, carbohydrates on board, and insulin on board as input to predict interstitial glucose (IG). The proposed model may be used for predicting IG even during physical activity (PA). A population-based model, obtained from a first database composed of 14 type 1 diabetes (T1D) patients, achieved a root-mean-square error (RMSE) of 16 . 7 ± 15 . 6 mg/dL, on IG prediction (30-min ahead) at the end of a PA, on a second database (15 T1D patients). Patient-specific ARX models, obtained on the second database, improved prediction accuracy (RMSE = 7 . 8 ± 4 . 5 mg/dL), outperforming the results found in the literature.

We used data from the GUIDANCE Study to determine the care of people with type 2 diabetes according to age and accompanying cardiovascular diseases and to assess indicators of overtreatment of glycaemia. The GUIDANCE study was a retrospective, cross-sectional study from 2009–2010 based on the records of 7597 people in France, Belgium, Italy, the Netherlands, Sweden, UK, Ireland and Germany. We analysed the level of metabolic control achieved and blood glucose-lowering medication used in different age groups and in relation to accompanying diseases. 4.459 patients (59.1%) were 65 years or older. Their HbA1c levels were similar to those with

Leelarathna et al. (1) report a retrospective analysis linking the duration of hybrid closed-loop insulin therapy, using a single algorithm, with the achievement of stable sensor glucose metrics. They found that in adults with type 1 diabetes and baseline HbA1c ≥58 mmol/mol (≥7.5%), it takes 4 weeks to observe representative data for mean glucose and percentage time spent in normoglycemia and hyperglycemia. They also suggest that 6 weeks’ duration may be required for reliable estimates of hypoglycemia and glucose variability. This time may be required for control algorithm individualization and behavioral adaptation. We looked at the database built during the multicentric trial (WP7) that tested the Diabeloop DBLG1 hybrid closed-loop system in 63 adult patients with type 1 diabetes (baseline …

Objective: Availability of closed-loop insulin delivery systems is expected by patients with type 1 diabetes. Our main objective was to assess whether patients using the Diabeloop artificial pancreas system could achieve a better glucose control compared to sensor-assisted pump therapy, as measured by percentage time in range 70-180 mg/dl. Methods: A multicenter clinical trial was conducted in a home setting, using an MPC-based algorithm, a hybrid monohormonal system (CellNovo® pump and Dexcom G5® sensor) and centralised remote monitoring. Adult patients with T1D for ≥ 2 years, pump therapy for ≥ 6 months, HbA1c ≤ 10%, and preserved hypoglycemia awareness were included among 12 investigation centers. Design was a crossover trial with a 2-week run-in period, followed by 2 sequences of 12 weeks each separated with washout. Results of the first 12-week arm are reported. Results: 68 patients (27 men, age 47.2±13.4 years, HbA1c 7.6±0.9%, duration of disease 27.9±13.2 years) were randomised between closed-loop (CL, n=33) and open-loop (OL, n=35) first. During the first 12-week period, time spent in the 70-180 mg/dl range was 69.5% [62.4;75.6] in CL vs. 58.7% [45.2;64.9] in OL. Time in hypoglycaemia Conclusion: The Diabeloop closed-loop system was efficient regarding metabolic outcomes. Disclosure S. Franc: Consultant; Self; Animas Corporation, Roche Diabetes Care Health and Digital Solutions, Johnson & Johnson Diabetes Institute, LLC. P.Y. Benhamou: Consultant; Self; Abbott, Sanofi, Novo Nordisk Inc.. Other Relationship; Self; Eli Lilly and Company, Roche Diabetes Care Health and Digital Solutions. Advisory Panel; Self; Diabeloop S.A. S. Borot: Consultant; Self; Abbott, Animas Corporation, Johnson & Johnson Diabetes Institute, LLC., Medtronic, Roche Diabetes Care Health and Digital Solutions. L. Chaillous: None. B. Delemer: Other Relationship; Self; Sanofi-Aventis, Eli Lilly and Company. B. Guerci: None. H. Hanaire: Consultant; Self; Abbott, Animas Corporation, Johnson & Johnson Diabetes Institute, LLC., Medtronic, Roche Diabetes Care Health and Digital Solutions. N.M. Jeandidier: Board Member; Self; Sanofi-Aventis. E. Renard: Advisory Panel; Self; Abbott. Board Member; Self; Eli Lilly and Company, Insulet Corporation, Novo Nordisk A/S, Sanofi, Roche Pharma. Consultant; Self; Air Liquide. Research Support; Self; Roche Pharma, Dexcom, Inc., TypeZero Technologies, Inc.. Y. Reznik: None. P. Schaepelynck: Consultant; Self; Roche Diabetes Care Health and Digital Solutions. Speaker's Bureau; Self; Medtronic MiniMed, Inc.. Board Member; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Sanofi-Aventis, Abbott, Eli Lilly and Company. C. Thivolet: Advisory Panel; Self; Abbott, Sanofi-Aventis, Medtronic MiniMed, Inc. G. Charpentier: Consultant; Self; Abbott, Dexcom, Inc., Medtronic.

Improvement in closed-loop insulin delivery systems could result from customization of settings to individual needs and remote monitoring. This pilot home study evaluated the efficacy and relevance of this approach. A bicentric clinical trial was conducted for 3 weeks, using an MPC-based algorithm (Diabeloop Artificial Pancreas system) featuring five settings designed to modulate the reactivity of regulation. Remote monitoring was ensured by expert nurses with a web platform generating automatic Secured Information Messages (SIMs) and with a structured procedure. Endpoints were glucose metrics and description of impact of monitoring on regulation parameters. Eight patients with type 1 diabetes (six men, age 41.8 ± 11.4 years, HbA1c 7.7 ± 1.0%) were included. Time spent in the 70–180 mg/dl range was 70.2% [67.5; 76.9]. Time in hypoglycemia

OBJECTIVE To compare the efficacy and safety of once-weekly semaglutide 1.0 mg s.c. with exenatide extended release (ER) 2.0 mg s.c. in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS In this phase 3a, open-label, parallel-group, randomized controlled trial, 813 subjects with type 2 diabetes taking oral antidiabetic drugs were randomized (1:1) to semaglutide 1.0 mg or exenatide ER 2.0 mg for 56 weeks. The primary end point was change from baseline in HbA1c at week 56. RESULTS Mean HbA1c (8.3% [67.7 mmol/mol] at baseline) was reduced by 1.5% (16.8 mmol/mol) with semaglutide and 0.9% (10.0 mmol/mol) with exenatide ER (estimated treatment difference vs. exenatide ER [ETD] –0.62% [95% CI –0.80, –0.44] [–6.78 mmol/mol (95% CI –8.70, –4.86)]; P < 0.0001 for noninferiority and superiority). Mean body weight (95.8 kg at baseline) was reduced by 5.6 kg with semaglutide and 1.9 kg with exenatide ER (ETD –3.78 kg [95% CI –4.58, –2.98]; P < 0.0001). Significantly more subjects treated with semaglutide (67%) achieved HbA1c CONCLUSIONS Semaglutide 1.0 mg was superior to exenatide ER 2.0 mg in improving glycemic control and reducing body weight after 56 weeks of treatment; the drugs had comparable safety profiles. These results indicate that semaglutide treatment is highly effective for subjects with type 2 diabetes who are inadequately controlled on oral antidiabetic drugs.

Introduction The aim of this study was to investigate whether the efficacy of liraglutide observed in randomized controlled trials translates into therapeutic benefits in the French population during routine clinical practice. Methods This observational, prospective, multicenter study included 3152 adults with type 2 diabetes who had recently started or were about to start liraglutide treatment. During 2 years of follow-up, an evaluation of the reasons for prescribing liraglutide, maintenance dose of liraglutide, changes in combined antidiabetic treatments, level of glycemic control, change in body weight and body mass index (BMI), patient satisfaction with diabetes treatment and safety of liraglutide were investigated. The primary study endpoint was the proportion of patients still receiving liraglutide and presenting with HbA1c

International audience; AIMS/HYPOTHESIS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a critical regulator of cholesterol homeostasis. PCSK9 inhibitors are being actively developed to lower LDL-cholesterol levels. However, there are conflicting data regarding the consequences of Pcsk9 deficiency on glucose homeostasis in mouse models. Here, we analysed in humans the association between the PCSK9 p.R46L loss-of-function (LOF) variant and (1) glucose homeostasis variables; (2) type 2 diabetes status; and (3) the risk of 9 year incident type 2 diabetes in a prospective study. METHODS: PCSK9 p.R46L was genotyped in 4630 French participants from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study and in 1342 French participants with type 2 diabetes. The association between p.R46L and metabolic traits or type 2 diabetes risk was assessed through linear or logistic regression models adjusted for age, sex and BMI. The association between p.R46L and incident type 2 diabetes was assessed using a Cox regression model adjusted for sex, age and BMI at baseline. RESULTS: Significant associations (p \textless 10(-6)) were found between p.R46L and lower total cholesterol (-0.394 mmol/l), LDL-cholesterol (-0.393 mmol/l) and apolipoprotein B concentrations (-0.099 g/l). However, no significant association was observed between p.R46L and markers of glucose homeostasis (including fasting glucose, fasting insulin, HbA1c, HOMA-B, HOMA-IR) or type 2 diabetes risk. Furthermore, no significant association between p.R46L variant and risk of incident type 2 diabetes was observed in DESIR. CONCLUSIONS/INTERPRETATION: The PCSK9 p.R46L LOF variant was not associated with impaired glucose homeostasis in humans. These data are reassuring regarding the safety of PCSK9 inhibitors.

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

Objective The aim of this study was to evaluate the prevalence of accurate self-knowledge of a patient’s own HbA1c level (HbA1c SK ), as a component of structural education (University Hospital's of Leicester (UHL), 2013) and its association with glycaemic control. Methods Data from the GUIDANCE study, a cross-sectional study involving 7597 participants from eight European countries was used. HbA1c SK was evaluated and compared with laboratory measured HbA1c levels (HbA1c LAB ), which represented the measure of glycaemic control. Accuracy of the self-reported HbA1c was evaluated by using agreement statistical methods. Results The prevalence of HbA1c SK was 49.4%. Within this group, 78.3% of the participants had accurately reported HbA1c SK . There was good level of agreement between HbA1c SK and HbA1c LAB (intra-class correlation statistic = 0.84, p SK were found to have a statistically significantly lower HbA1c LAB compared to participants with inaccurately reported HbA1c SK (7.0% versus 7.3%, p Conclusion Nearly half of the patients had self-knowledge of their own HbA1c level. Moreover, the participants with accurately reported HbA1c SK were found to have associated better glycaemic control.

Objective: There is room for improvement in the algorithms used in closed-loop insulin therapy during the prandial period. This pilot study evaluated the efficacy and safety of the Diabeloop algorithm (model predictive control type) during the postprandial period. Methods: This 2-center clinical trial compared interstitial glucose levels over two 5-hour periods (with/without the algorithm) following a calibrated lunch. On the control day, the amount of insulin delivered by the pump was determined according to the patient’s usual parameters. On the test day, 50% or 75% of the theoretical bolus required was delivered, while the algorithm, informed of carbohydrate intake, proposed changes to insulin delivery every 15 minutes using modeling to forecast glucose levels. The primary endpoint was percentage of time spent at near normoglycemia (70-180 mg/dl). Results: Twelve patients with type 1 diabetes (9 men, age 35.6 ± 12.7 years, HbA1c 7.3 ± 0.8%) were included. The percentage of time spent in the target range was 84.5 ± 20.8 (test day) versus 69.2 ± 33.9% (control day, P = .11). The percentage of time spent in hypoglycemia < 70 mg/dl was 0.2 ± 0.8 (test) versus 4.4 ± 8.2% (control, P = .18). Interstitial glucose at the end of the test (5 hours) was 127.5 ± 40.1 (test) versus 146 ± 53.5 mg/dl (control, P = .25). The insulin doses did not differ, and no differences were observed between the 50% and 75% boluses. Conclusion: In a semi-closed-loop configuration with manual priming boluses (25% or 50% reduction), the Diabeloop v1 algorithm was as successful as the manual method in determining the prandial bolus, without any exposure to excessive hypoglycemic risk.

SummaryAims Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of type 2 diabetes mellitus (T2DM). This randomised, double-blind, placebo-controlled, Phase 3 study evaluated the efficacy and safety of canagliflozin as an add-on to metformin plus sulphonylurea in patients with T2DM. Methods Patients (N = 469) received canagliflozin 100 or 300 mg or placebo once daily during a 26-week core period and a 26-week extension. Prespecified primary end-point was change in HbA1c at 26 weeks. Secondary end-points included change in HbA1c at week 52 as well as proportion of patients achieving HbA1c

Introduction The objective of this subgroup analysis is to investigate the effectiveness of liraglutide in people with type 2 diabetes (T2D) treated within the primary care physician (PCP) and specialist care settings. Methods EVIDENCE is a prospective, observational study of 3152 adults with T2D recently starting or about to start liraglutide treatment in France. We followed patients in the PCP and specialist settings for 2 years to evaluate the effectiveness of liraglutide in glycemic control and body weight reduction. Furthermore, we evaluated the changes in combined antihyperglycemic treatments, the reasons for prescribing liraglutide, patient satisfaction, and safety of liraglutide in these two treatment settings. Results After 2 years of follow-up, 477 out of 1209 (39.0%) of PCP and 297 out of 1398 (21.2%) of specialist-treated patients still used liraglutide and maintained the glycated hemoglobin (HbA1c) target of

International audience; Insulin pump users worldwide depend on insulin infusion sets (IISs) for predictable delivery of insulin to the subcutaneous tissue. Yet emerging data indicates that IISs are associated with many pump-related adverse events and may contribute to potentially life-threatening problem of unexplained hyperglycemia. The relative scarcity of published research on IISs to date, the heterogeneity of regional IIS practices, and the increasing demand for international standards guiding their use prompted convening of a panel of diabetologists and diabetes nurse educators last February, in Milan, Italy, to discuss a framework for optimizing IIS practice in Europe. The multinational panel was tasked, first, with identifying the often-overlooked IIS issues that can affect patients' experience of pump therapy-e.g., partial or complete blockage of the cannula, skin pathologies, unpredictable variations in insulin absorption, dislodgment, and the demands of site rotation and set changes-and, second, with establishing direction for developing cohesive protocols to assure long-term success. As reported in this article, the panel examined IIS-related complications of pump therapy encountered in clinical practice, considered country-wide policies to prevent and mitigate such complications, and updated priorities for improving IIS education on issues of device selection, skin care, and troubleshooting unexplained hyperglycemia. These recommendations may be more relevant with the possibility of closed-loop systems available in the near future.

Microvascular complications are a common feature of diabetes but additional research is needed regarding diabetic nephropathy endpoints in type 1 and type 2 diabetes. We compared 277 type 1 diabetes patients with 942 type 2 diabetes patients, with clinical proteinuria and no end-stage renal disease (ESRD) at baseline, prospectively followed for death, ESRD and decline in estimated glomerular filtration rate (eGFR, all available measures). The incidence rate of death was 67.0 (95% CI 59.2, 74.8) vs 24.6 (95% CI, 19.0, 30.2) per 1,000 patient-years, in type 2 diabetes and type 1 diabetes, respectively. Unadjusted risk for death was greater for type 2 diabetes patients (HR 3.423; 95% CI, 2.501, 4.683; p

OBJECTIVE The benefits of real-time continuous glucose monitoring (CGM) have been demonstrated in patients with type 1 diabetes. Our aim was to compare the effect of two modes of use of CGM, patient led or physician driven, for 1 year in subjects with poorly controlled type 1 diabetes. RESEARCH DESIGN AND METHODS Patients with type 1 diabetes aged 8–60 years with HbA1c ≥8% were randomly assigned to three groups (1:1:1). Outcomes for glucose control were assessed at 1 year for two modes of CGM (group 1: patient led; group 2: physician driven) versus conventional self-monitoring of blood glucose (group 3: control). RESULTS A total of 257 subjects with type 1 diabetes underwent screening. Of these, 197 were randomized, with 178 patients completing the study (age: 36 ± 14 years; HbA1c: 8.9 ± 0.9%). HbA1c improved similarly in both CGM groups and was reduced compared with the control group (group 1 vs. group 3: −0.52%, P = 0.0006; group 2 vs. group 3: −0.47%, P = 0.0008; groups 1 + 2 vs. group 3: −0.50%, P < 0.0001). The incidence of hypoglycemia was similar in the three groups. Patient SF-36 questionnaire physical health score improved in both experimental CGM groups (P = 0.004). Sensor consumption was 34% lower in group 2 than in group 1 (median [Q1–Q3] consumption: group 1: 3.42/month [2.20–3.91] vs. group 2: 2.25/month [1.27–2.99], P = 0.001). CONCLUSIONS Both patient-led and physician-driven CGM provide similar long-term improvement in glucose control in patients with poorly controlled type 1 diabetes, but the physician-driven CGM mode used fewer sensors.

OBJECTIVE Gain-of-function ABCC8/sulfonylurea (SU) receptor 1 mutations cause neonatal diabetes mellitus (NDM) or late-onset diabetes in adult relatives. Given the effectiveness of SU treatment in ABCC8-NDM patients, we further characterized late-onset ABCC8-associated diabetes. RESEARCH DESIGN AND METHODS Seven adult subjects from three NDM families and one family with type 2 diabetes were studied. Insulin secretion and insulin sensitivity were assessed using clamp techniques. We screened 139 type 2 diabetic patients who were well controlled by SU for ABCC8 mutations. RESULTS ABCC8 mutation carriers exhibited glucose intolerance, frank diabetes, or insulin-requiring diabetes since diagnosis. HbA1c improved in five SU-treated patients. Insulin secretion capacity was impaired in three patients compared with adult control subjects but was restored after a 4-week SU trial in two patients. Cohort screening revealed four SU-treated patients with ABCC8 mutations, two of which are likely causal. CONCLUSIONS Although of rare occurrence, recognition of adult-onset ABCC8-associated diabetes may help in targeting patients for SU therapy.

Obesity is the major determinant of type 2 diabetes (T2D), presumably through its effect on insulin resistance. Genome-wide association studies reported many single-nucleotide polymorphisms (SNPs) that increase obesity risk and body mass index (BMI), but their impact on T2D-related traits and risk is unclear.We aimed at analyzing the effect of 24 obesity risk alleles, separately and in combination, on variation of both insulin resistance and β-cell dysfunction, and on T2D risk.We genotyped 24 obesity-associated SNPs and calculated an obesity genotype score (sum of the obesity risk alleles per individual). We analyzed the contribution of each SNP and this score to the variation of four metabolic indices: homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of the pancreatic β-cell function (HOMA-B), insulin sensitivity index (ISI) and insulinogenic index (II) (in up to 8050 nondiabetic French individuals) and to T2D risk (in 2077 T2D cases and 3085 controls).We found a highly significant effect of the obesity genotype score on increased insulin resistance adjusted for age and gender (β=0.02; P-value=7.16 × 10(-9) for HOMA-IR). Individually, we identified nominal or significant association between increased insulin resistance and risk alleles in FAIM2, FTO, GNPDA2, MC4R, NPC1, PTER and SH2B1. Most signals, including the obesity genotype score and FTO SNP, were also associated with increased β-cell function (β=0.01; P-value=1.05 × 10(-6) and β=0.04; P-value=3.45 × 10(-4), respectively). In our T2D case-control study, only the obesity genotype score and the well-known FTO locus significantly contributed to T2D risk (OR=1.03; P-value=9.99 × 10(-3) and OR=1.15; P-value=9.46 × 10(-4), respectively). Adjustment for BMI abolished all significant associations.Genetic predisposition to obesity contributes to increased insulin resistance and to its compensation through increased β-cell function, and weakly increases the T2D risk. These associations are mediated by BMI.

Health authorities currently have high expectations for telemedicine (TM), as it addresses several major challenges: to improve access to healthcare (especially for patients in underserved or remote areas); to overcome the scarcity of specialists faced with epidemic disease; and to reduce the costs of healthcare while improving quality. The aims of TM in the field of diabetes differ according to the type of diabetes. In type 1 diabetes (T1DM) associated with complex insulin regimens, the goal of TM is to help patients achieve better control of their blood glucose levels through accurate adjustment of insulin doses. In type 2 diabetes (T2DM), while therapeutic adjustments may be necessary, improvement in blood glucose control is based primarily on behavioural changes (reduced calorie and carbohydrate intakes, increased physical activity). Many TM studies focusing on management of blood glucose levels have been published, but most failed to demonstrate any superiority of TM vs traditional care. While previously published meta-analyses have shown a slight advantage at best for TM, these meta-analyses included a mix of studies of varying durations and different populations (both T1DM and T2DM patients, adults and children), and tested systems of inconsistent quality. Studies published to date on TM suggest two currently promising approaches. First, handheld communicating devices, such as smartphones, loaded with software to apply physicians' prescriptions, have been shown to improve glycaemic control. These systems provide immediate assistance to the patient (such as insulin-dose calculation and food choice optimization at meals), and all data stored in the smartphone can be transmitted to authorized caregivers, enabling remote monitoring and even teleconsultation. These systems, initially developed for T1DM, appear to offer many possibilities for T2DM, too. Second, systems combining an interactive Internet system (or a mobile phone coupled to a remote server) with a system of communication between the healthcare provider and the patient by e-mail, texting or phone calls have also shown certain benefits for glycaemic control. These systems, primarily aimed at T2DM patients, generally provide motivational support as well. Although the individual benefits of these systems for glycaemic control are fewer than with smartphones, their widespread use should be of particular value for overcoming the relative shortage of doctors and reducing the health costs associated with a disease of such epidemic proportions.

The Coalition for Clinical Research--Self-Monitoring of Blood Glucose Scientific Board convened a meeting in San Francisco, CA, July 20-21, 2011, to discuss the current practice of self-monitoring of blood glucose (SMBG) in non-insulin-treated (NIT) type 2 diabetes mellitus (T2DM). Twelve physician panel members from academia, practice, and government attended this meeting. These experts came from the United States, Brazil, Canada, France, Germany, Italy, and the United Kingdom. In addition, three consultants from Australia, Germany, and the United States contributed to the group's final report. This coalition was organized by Diabetes Technology Society. Self-monitoring of blood glucose was studied from eight perspectives related to patients with NIT T2DM: (1) epidemiological studies; (2) randomized controlled trials (RCT)s and meta-analyses; (3) targets, timing, and frequency of SMBG use; (4) incidence and role of SMBG in preventing hypoglycemia with single-drug regimens and combination regimens consisting of antihyperglycemic agents other than secretagogues and insulin; (5) comparison of SMBG with continuous glucose monitoring; (6) technological capabilities and limitations of SMBG; (7) barriers to appropriate use of SMBG; and (8) methods and end points for appropriate future clinical trials. The panel emphasized recent studies, which reflect the current approach for applying this intervention. Among the participants there was consensus that: SMBG is an established practice for patients with NIT T2DM, and to be most effective, it should be performed in a structured format where information obtained from this measurement is used to guide treatment; New, high-quality efficacy data from RCTs have demonstrated efficacy of SMBG in NIT T2DM in trials reported since 2008; Both patients and health care professionals require education on how to respond to the data for SMBG to be effective; and Additional well-defined studies are needed to assess the benefits and costs of SMBG with end points not limited to hemoglobin A1c.

OBJECTIVE To demonstrate that Diabeo software enabling individualized insulin dose adjustments combined with telemedicine support significantly improves HbA1c in poorly controlled type 1 diabetic patients. RESEARCH DESIGN AND METHODS In a six-month open-label parallel-group, multicenter study, adult patients (n = 180) with type 1 diabetes (>1 year), on a basal-bolus insulin regimen (>6 months), with HbA1c ≥8%, were randomized to usual quarterly follow-up (G1), home use of a smartphone recommending insulin doses with quarterly visits (G2), or use of the smartphone with short teleconsultations every 2 weeks but no visit until point end (G3). RESULTS Six-month mean HbA1c in G3 (8.41 ± 1.04%) was lower than in G1 (9.10 ± 1.16%; P = 0.0019). G2 displayed intermediate results (8.63 ± 1.07%). The Diabeo system gave a 0.91% (0.60; 1.21) improvement in HbA1c over controls and a 0.67% (0.35; 0.99) reduction when used without teleconsultation. There was no difference in the frequency of hypoglycemic episodes or in medical time spent for hospital or telephone consultations. However, patients in G1 and G2 spent nearly 5 h more than G3 patients attending hospital visits. CONCLUSIONS The Diabeo system gives a substantial improvement to metabolic control in chronic, poorly controlled type 1 diabetic patients without requiring more medical time and at a lower overall cost for the patient than usual care.

In a previous pilot study comparing insulin glulisine (GLU) with insulin aspart (ASP) administered by continuous subcutaneous insulin infusion (CSII), GLU-treated patients did show a trend toward fewer catheter occlusions compared with ASP-treated patients. Here we performed a randomized open-label, three-way crossover, controlled multicenter study comparing GLU with ASP and insulin lispro (LIS). Subjects with type 1 diabetes were allocated to one of three treatment orders-GLU-ASP-LIS, ASP-LIS-GLU, or LIS-GLU-ASP-with each insulin used for 13 weeks. The study was designed to demonstrate the superiority of GLU over ASP and LIS on unexplained hyperglycemia and/or perceived infusion set occlusion. A prespecified P value of 0.025 was considered significant to correct for multiple testing. Percentages of subjects with at least one unexplained hyperglycemia and/or infusion set occlusion were not significantly different between GLU and ASP (68.4% [62.7-74.1%] vs. 62.1% [56.2-68.1%], P = 0.04) and GLU and LIS (68.4% [62.7-74.1%] vs. 61.3% [55.4-67.3%], P = 0.03). No differences were seen in hemoglobin A1c at end point, most points of the seven-point glucose curves, severe hypoglycemia, and symptomatic ketoacidosis. The overall rate of hypoglycemia with a plasma glucose level below 70 mg/dL per patient-year was significantly different between GLU and ASP (73.84 vs. 65.01, P = 0.008) and GLU and LIS (73.84 vs. 62.69, P

OBJECTIVE We investigated the relationship between carbohydrate intake and postprandial blood glucose (BG) levels to determine the most influential meal for type 2 diabetic subjects treated with basal insulin and needing prandial insulin. RESEARCH DESIGN AND METHODS Three-day BG profiles for 37 type 2 diabetic subjects, with A1C levels of 7.7%, treated with sulfonylurea and metformin, and well titrated on insulin glargine, were analyzed using a continuous glucose monitoring system. Food intake from 680 meals was recorded and quantified during continuous glucose monitoring. RESULTS The median BG excursion (ΔBG) was higher at breakfast than at lunch or dinner (111 [81; 160] vs. 69.5 [41.5; 106] and 82.5 mg/dl [53; 119] mg/dl, P < 0.0001). There was a weak overall correlation between ΔBG and carbohydrate intake. Correlation improved when mealtime was taken into account. Simple relationships were established: ΔBG (mg/dl) = 65 × carbohydrate/body weight + 73 for breakfast (R2 = 0.20, P < 0.0001); the slope was reduced by half at lunch and by one-third at dinner. Twelve relevant variables likely to affect ΔBG were integrated into a polynomial equation. This model accounted for 49% of ΔBG variability. Two groups of patients were identified: responders, in whom ΔBG was well correlated with carbohydrate intake (R2 ≥ 0.30, n = 8), and nonresponders (R2 < 0.30, n = 29). Responders exhibited a greater insulinopenic profile than nonresponders. CONCLUSIONS The carbohydrate intake in responders clearly drives ΔBG, whereas, in nonresponders, other factors predominate. This sort of characterization should be used to guide therapeutic choices toward more targeted care with improved type 2 diabetes management.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46, 186 nondiabetic participants. Follow-up of 25 loci in up to 76, 558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

OBJECTIVE A1C is widely considered the gold standard for monitoring effective blood glucose levels. Recently, a genome-wide association study reported an association between A1C and rs7072268 within HK1 (encoding hexokinase 1), which catalyzes the first step of glycolysis. HK1 deficiency in erythrocytes (red blood cells [RBCs]) causes severe nonspherocytic hemolytic anemia in both humans and mice. RESEARCH DESIGN AND METHODS The contribution of rs7072268 to A1C and the RBC-related traits was assessed in 6,953 nondiabetic European participants. We additionally analyzed the association with hematologic traits in 5,229 nondiabetic European individuals (in whom A1C was not measured) and 1,924 diabetic patients. Glucose control–related markers other than A1C were analyzed in 18,694 nondiabetic European individuals. A type 2 diabetes case-control study included 7,447 French diabetic patients. RESULTS Our study confirms a strong association between the rs7072268–T allele and increased A1C (β = 0.029%; P = 2.22 × 10−7). Surprisingly, despite adequate study power, rs7072268 showed no association with any other markers of glucose control (fasting- and 2-h post-OGTT–related parameters, n = 18,694). In contrast, rs7072268–T allele decreases hemoglobin levels (n = 13,416; β = −0.054 g/dl; P = 3.74 × 10−6) and hematocrit (n = 11,492; β = −0.13%; P = 2.26 × 10−4), suggesting a proanemic effect. The T allele also increases risk for anemia (836 cases; odds ratio 1.13; P = 0.018). CONCLUSIONS HK1 variation, although strongly associated with A1C, does not seem to be involved in blood glucose control. Since HK1 rs7072268 is associated with reduced hemoglobin levels and favors anemia, we propose that HK1 may influence A1C levels through its anemic effect or its effect on glucose metabolism in RBCs. These findings may have implications for type 2 diabetes diagnosis and clinical management because anemia is a frequent complication of the diabetes state.