Heterogeneity of glycaemic phenotypes in type 1 diabetes.

AIMS/HYPOTHESIS: Our study aims to uncover glycaemic phenotype heterogeneity in type 1 diabetes. METHODS: In the Study of the French-speaking Society of Type 1 Diabetes (SFDT1), we characterised glycaemic heterogeneity thanks to a set of complementary metrics: HbA1c, time in range (TIR), time below range (TBR), CV, Gold score and glycaemia risk index (GRI). Applying the Discriminative Dimensionality Reduction with Trees (DDRTree) algorithm, we created a phenotypic tree, i.e. a 2D visual mapping. We also carried out a clustering analysis for comparison. RESULTS: We included 618 participants with type 1 diabetes (52.9% men, mean age 40.6 years [SD 14.1]). Our phenotypic tree identified seven glycaemic phenotypes. The 2D phenotypic tree comprised a main branch in the proximal region and glycaemic phenotypes in the distal areas. Dimension 1, the horizontal dimension, was positively associated with GRI (coefficient [95% CI]) (0.54 [0.52, 0.57]), HbA1c (0.39 [0.35, 0.42]), CV (0.24 [0.19, 0.28]) and TBR (0.11 [0.06, 0.15]), and negatively with TIR (-0.52 [-0.54, -0.49]). The vertical dimension was positively associated with TBR (0.41 [0.38, 0.44]), CV (0.40 [0.37, 0.43]), TIR (0.16 [0.12, 0.20]), Gold score (0.10 [0.06, 0.15]) and GRI (0.06 [0.02, 0.11]), and negatively with HbA1c (-0.21 [-0.25, -0.17]). Notably, socioeconomic factors, cardiovascular risk indicators, retinopathy and treatment strategy were significant determinants of glycaemic phenotype diversity. The phenotypic tree enabled more granularity than traditional clustering in revealing clinically relevant subgroups of people with type 1 diabetes. CONCLUSIONS/INTERPRETATION: Our study advances the current understanding of the complex glycaemic profile in people with type 1 diabetes and suggests that strategies based on isolated glycaemic metrics might not capture the complexity of the glycaemic phenotypes in real life. Relying on these phenotypes could improve patient stratification in type 1 diabetes care and personalise disease management.

Beneficial Effects of Two Marine Oxygen Carriers, M101 and M201, on Human Islet Quality in Hypoxic Culture Conditions.

High pancreatic islet sensitivity to hypoxia is an important issue in the field of pancreatic islet transplantation. A promising strategy to improve islet oxygenation in hypoxic conditions is to leverage the properties of hemoglobin as a natural carrier of oxygen. Studies using human or bovine hemoglobin have failed to demonstrate efficacy, probably due to the molecule being unstable in the absence of protective erythrocytes. Recently, marine worm hemoglobins have been shown to be more stable and to possess higher oxygen carrier potential, with 156 oxygen binding sites per molecule compared to four in humans. Previous studies have shown the beneficial effects of two marine worm hemoglobins, M101 and M201, on nonhuman pancreatic islets. However, their effects on human islets have not been tested or compared. In this study, we assessed the impact of both molecules during human islet culture in vitro under hypoxic conditions. Human islets were exposed to both molecules for 24 h in high islet density-induced hypoxia [600 islet equivalents (IEQ)/cm²]. M101 and M201 reduced the release of hypoxic (VEGF) and apoptotic (cyt c) markers in the medium after 24-h culture. Human islet function or viability was improved in vitro in the presence of these oxygen carriers. Thus, the utilization of M101 or M201 could be a safe and easy way to improve human islet oxygenation and survival in hypoxic conditions as observed during islet culture prior to transplantation or islet encapsulation.

An Unsafe/Safe Typology in People with Type 2 Diabetes: Bridging Patients' Expectations, Personality Traits, Medication Adherence, and Clinical Outcomes.

Background: Support programs are provided to people with diabetes to help them manage their disease. However, adherence to and persistence in support programs are often low, making it difficult to demonstrate their effectiveness. Aim: To identify the determinants of patients' perceived interest in diabetes support programs because it may be a powerful determinant of effective participation in such programs. Patients and Methods: An online study conducted in April 2021 in metropolitan France on 600 people with diabetes recruited from a consumer panel. A 64-item psychosocial questionnaire including a question asking to evaluate the helpfulness of a support program was used. Univariate, multivariate, and multiple correspondence analyses were performed. Results: The existence of a typology, known as Unsafe/Safe, was discovered, in which patients with type 2 diabetes respond in two distinct ways. Type U (unsafe) patients, who believe that a support program would be helpful, are more likely to be nonadherent to their treatment, have high hemoglobin A1c levels, have at least one diabetic complication, lack information regarding their disease and treatment, rate the burden of their disease and impairment of their quality of life as high, worry about their future, and are pessimistic. Type S (safe) patients have the opposite characteristics. Type U patients can be dichotomized into two broad classes: one in which they lack information regarding disease and treatment and the other in which alterations in the quality of life and burden of the disease predominate. Insulin-treated patients give more importance to the lack of information, whereas noninsulin-treated patients complain primarily about the burden of the disease and impairment of quality of life. Conclusion: This study describes this new U/S typology, proposes a simple method based on a nine-item questionnaire to identify type U patients by calculating a Program Helpfulness Score described herein, and clarifies the nature of the intervention to be provided to them. This novel approach could be applied to other chronic diseases.

Prospective Independent Evaluation of the Carbohydrate Counting Accuracy of Two Smartphone Applications.

INTRODUCTION: Smartphone applications (apps) have been designed that help patients to accurately count their carbohydrate intake in order to optimize prandial insulin dose matching. Our aim was to evaluate the accuracy of two carbohydrate (carb) counting apps. METHODS: Medical students, in the role of mock patients, evaluated meals using two smartphone apps: Foodvisor® (which uses automatic food photo recognition technology) and Glucicheck® (which requires the manual entry of carbohydrates with the help of a photo gallery). The macronutrient quantifications obtained with these two apps were compared to a reference quantification. RESULTS: The carbohydrate content of the entire meal was underestimated with Foodvisor® (Foodvisor® quantification minus gold standard quantification = - 7.2 ± 17.3 g; p < 0.05) but reasonably accurately estimated with Glucicheck® (Glucicheck® quantification minus gold standard quantification = 1.4 ± 13.4 g; ns). The percentage of meals with an absolute error in carbohydrate quantification above 20 g was greater for Foodvisor® compared to Glucicheck® (30% vs 14%; p < 0.01). CONCLUSION: The carb counting accuracy was slightly better when using Glucicheck® compared to Foodvisor®. However, both apps provided a lower mean absolute carb counting error than that usually made by T1D patients in everyday life, suggesting that such apps may be a useful adjunct for estimating carbohydrate content.

No more hypoglycaemia on days with physical activity and unrestricted diet when using a closed-loop system for 12 weeks: A post hoc secondary analysis of the multicentre, randomized controlled Diabeloop WP7 trial.

A post hoc analysis of the Diabeloop WP7 multicentre, randomized controlled trial was performed to investigate the efficacy of the Diabeloop Generation-1 (DBLG1) closed-loop system in controlling the hypoglycaemia induced by physical activity (PA) in real-life conditions. 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). Daily time spent in the interstitial glucose range less than 70 mg/dL was not significantly different between days with and without PA (2.0% ± 1.5% vs. 2.2% ± 1.1%), regardless of the intensity or duration of the PA. Preventive CHO intake recommended by the system was significantly higher in days with PA (41.1 ± 35.5 vs. 21.8 ± 28.5 g/day; P < .0001), and insulin delivery was significantly lower (31.5 ± 10.5 vs. 34.0 ± 10.5 U/day; P < .0001). The time spent in hyperglycaemia and the glycaemic variation coefficient increased significantly on days with PA. In real-life conditions, the use of DBLG1 avoids PA-induced hypoglycaemia. Insulin adjustments and preventive CHO recommendation may explain this therapeutic benefit.

Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study.

AIMS/HYPOTHESIS: This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19). METHODS: The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days. RESULTS: We included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th-75th percentile) 28.4 (25.0-32.4) kg/m2. Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5-14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors. CONCLUSIONS/INTERPRETATION: In patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04324736.

Efficacy and safety of exenatide as add-on therapy for patients with type 2 diabetes with an intensive insulin regimen: A randomized double-blind trial.

AIM: To assess the safety and efficacy of the short-acting glucagon-like peptide-1 receptor agonist exenatide on a population of patients with type 2 diabetes (T2D) mostly treated with continuous subcutaneous insulin injection (CSII). MATERIALS AND METHODS: A phase 2/3, multicentre, randomized, parallel-group, double-blind, placebo-controlled, 6-month trial was conducted. Patients were randomized to receive subcutaneous (SC) injections of exenatide (10 µg BID) or matched placebo. RESULTS: A total of 46 patients with T2D and elevated HbA1c were randomized (42% of the planned sample size): exenatide (n = 28) and placebo (n = 18). CSII treatment was used by 75% and 89% of patients of the exenatide and placebo groups, respectively. At 6 months, the change in HbA1c was -0.62% ± 0.94% and 0.08% ± 0.81% in the exenatide and placebo groups, respectively (difference, -0.70%; 95% CI [-1.24%; -0.15%], P = .014); body weight and body mass index decreased in the exenatide group (-2.55 ± 3.25 kg and -1.00 ± 1.31 kg/m2 ) and increased in the placebo group (1.29 ± 2.82 kg and 0.46 ± 1.16 kg/m2 ) (observed difference, -3.85 and -1.45, respectively, both P < .001); the postdinner capillary blood glucose value was lower in the exenatide group compared with the placebo group (162.4 ± 80.5 vs. 259.1 ± 94.4 mg/dL, respectively; observed difference, -96.7, P < .01). Hypoglycaemic risk, quality of life and overall safety were not different between the groups, apart from the expected occurrence of digestive effects in the exenatide group. CONCLUSIONS: Although we failed to reach our planned sample size, the addition of exenatide treatment 10 µg BID SC in T2D patients with uncontrolled HbA1c despite an intensified insulin regimen, resulted in a significant reduction of HbA1c and body weight with a good overall safety profile and acceptance.

DIABEO System Combining a Mobile App Software With and Without Telemonitoring Versus Standard Care: A Randomized Controlled Trial in Diabetes Patients Poorly Controlled with a Basal-Bolus Insulin Regimen.

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.

Impact of Circadian Disruption on Female Mice Reproductive Function.

In female mammals, cycles in reproductive function depend both on the biological clock synchronized to the light/dark cycle and on a balance between the negative and positive feedbacks of estradiol, whose concentration varies during oocyte maturation. In women, studies report that chronodisruptive environments such as shiftwork may impair fertility and gestational success. The objective of this study was to explore the effects of shifted light/dark cycles on both the robustness of the estrous cycles and the timing of the preovulatory luteinizing hormone (LH) surge in female mice. When mice were exposed to a single 10-hour phase advance or 10-hour phase delay, the occurrence and timing of the LH surge and estrous cyclicity were recovered at the third estrous cycle. By contrast, when mice were exposed to chronic shifts (successive rotations of 10-hoursour phase advances for 3 days followed by 10-hour phase delays for 4 days), they exhibited a severely impaired reproductive activity. Most mice had no preovulatory LH surge at the beginning of the chronic shifts. Furthermore, the gestational success of mice exposed to chronic shifts was reduced, because the number of pups was 2 times lower in shifted than in control mice. In conclusion, this study reports that exposure of female mice to a single phase shift has minor reproductive effects, whereas exposure to chronically disrupted light/dark cycles markedly impairs the occurrence of the preovulatory LH surge, leading to reduced fertility.

A fully implantable device for diffuse insulin delivery at extraperitoneal site for physiological treatment of type 1 diabetes.

Intraperitoneal insulin delivery has higher benefits than subcutaneous insulin administration but has limitations, including obstruction of the catheter used in delivery devices. To overcome these limitations this study assessed safety and efficacy of an alternative approach involving a new delivery device, named ExOlin®, allowing diffuse release of insulin in the extraperitoneal site. The aim of this study is to validate both safety and efficacy of insulin delivery in extraperitoneal using ExOlin® device. Safety of the ExOlin® device implantation in the extraperitoneal site was investigated over a 3-month period in Wistar rat and landrace swine models before comparing efficacy pharmacokinetics and hepatic first-pass metabolism of insulin after focal delivery using a catheter or diffuse release via ExOlin® device in extraperitoneal. Implantation in rat and swine models demonstrated good integration of the device, validating the safety of the extraperitoneal site. In diabetic rats, direct insulin administration at the extraperitoneal showed an efficacy comparable to intraperitoneal and statistically significantly higher than subcutaneous route as shown by 23% lower AUC calculated from glycaemia profile. Diffuse extraperitoneal delivery of insulin via ExOlin® device in diabetic rats exhibited better efficacy than the subcutaneous route with up to six-fold lower peripheral insulin and higher hepatic first-pass than with intraperitoneal injection. Similar results were confirmed in the swine model after injecting insulin lispro via the device at the extraperitoneal site. In conclusion, diffuse administration of insulin at the extraperitoneal site via ExOlin® device is a new promising approach to physiologically treating type 1 diabetes. It can therefore be considered as a promising alternative to intraperitoneal route.

Liver adenomatosis in patients with hepatocyte nuclear factor-1 alpha maturity onset diabetes of the young (HNF1A-MODY): Clinical, radiological and pathological characteristics in a French series.

BACKGROUND: Liver adenomatosis (LA) is a rare disease resulting from biallelic inactivation of the hepatocyte nuclear factor-1 alpha (HNF1A) gene, which induces the proliferation of adenoma cells in liver parenchyma. Liver adenomatosis has only been documented in case reports from patients carrying a HNF1A germline mutation. We have evaluated the frequency of LA among a large cohort of patients with HNF1A-maturity onset diabetes of the young (MODY), previously termed "MODY3," and herein describe its clinical, radiological, and pathological characteristics. METHODS: In all, 137 HNF1A-MODY subjects from 74 families were screened by liver ultrasonography in 13 centers, and 15 additional cases of LA were later included in the series. Liver adenomatosis was confirmed by liver computed tomography, magnetic resonance imaging (MRI), and/or histopathology. RESULTS: Among 137 carriers of an HNF1A mutation, 9 patients (6.5%) from seven families were diagnosed with LA. Diabetes mellitus was present in 87.5% of patients with LA. In 25% of patients, LA was diagnosed due to intra-abdominal or intratumoral bleeding. Liver biochemistry was near normal in all patients. Liver imaging showed adenomas of various sizes and numbers. On MRI, most nodules had the radiological characteristics of steatotic adenomas. Histopathological confirmation of LA was available in 13 cases, and these adenomas were mostly steatotic. Surgery was initially performed in 37.5% of patients, and liver disease progression was observed in 30%. No disease progression was observed in 14 pregnancies. CONCLUSIONS: The frequency of LA in a cohort of screened HNF1A-MODY patients and the high incidence of LA progression and/or hemorrhage warrants systematic screening for liver adenomatosis in HNF1A-MODY families.

Efficacy of the Diabeloop closed-loop system to improve glycaemic control in patients with type 1 diabetes exposed to gastronomic dinners or to sustained physical exercise.

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.

Individual evaluation of luteinizing hormone in aged C57BL/6 J female mice.

In female mammals, reproductive senescence is a complex process involving progressive ovarian dysfunction associated with an altered central control of the hypothalamic-pituitary axis. The objective of this study was to compare the longitudinal change in preovulatory luteinizing hormone (LH) secretion as well as estrous cycle in individual C57BL/6 J female mice at 3, 6, 9 and 12 months. Amplitude and timing of LH secretion at the surge were similar from 3 to 9 months but were altered in 12-month old mice with a significant decrease of more than 50% of peak LH value and a 2 h delay in the occurrence of the LH surge as compared to younger mice. The analysis of two to three successive LH surges at 3, 6, 9 and 12 months showed low and similar intra-individual variability at all ages. The estrous cycle length and intra/inter variability were stable over the age. This study shows that female mice in regular environmental conditions display stable LH surge timing and amplitude up to 9 months, but at 12 months, the LH surge is delayed with a reduced amplitude, however without overt modification in the estrous cycles. Analysis of individual preovulatory LH secretion and estrous cycle indicates that mice can be followed up to 9 months to investigate the detrimental effects of various parameters on mouse reproductive activity.

Telemonitoring in diabetes: evolution of concepts and technologies, with a focus on results of the more recent studies.

This is a narrative review of telemonitoring (remote monitoring) projects and studies within the field of diabetes, with a focus on results of the more recent studies. Since the beginning of the 1990s, several telemedicine projects and studies focused on type 1 and type 2 diabetes. Over the last 5 years, numerous telemedicine projects based on connected objects and new information and communication technologies (ICT) (elements defining telemedicine 2.0) have emerged or are still under development. Two examples are the DIABETe and Telesage telemonitoring project which perfectly fits within the telemedicine 2.0 framework - the first to include artificial intelligence (AI) with MyPrediTM and DiabeoTM. Mainly, these projects and studies show that telemonitoring diabetic result in: improvements in control of blood glucose (BG) level and significant reduction in HbA1c (e.g., for Telescot et TELESAGE studies); positive impact on co-morbidities (arterial hypertension, weight, dyslipidemia) (e.g., for Telescot and DIABETe studies); better patient's quality of life (e.g., for DIABETe study); positive impact on appropriation of the disease by patients and/or greater adherence to therapeutic and hygiene-dietary measures (e.g., The Utah Remote Monitoring Project); and at least, good receptiveness by patients and their empowerment. To date, the magnitude of its effects remains debatable, especially with the variation in patients' characteristics (e.g., background, ability for self-management, medical condition), samples selection and approach for the treatment of control groups. All of the recent studies have been classified as "Moderate" to "High".

Iatrogenic hypoglycemia-related hospital admissions identified through databases: economic burden and causes.

Background Hypoglycemia is an acute and frequent complication of diabetes. Objectives To assess the number of hospital admissions due to iatrogenic hypoglycemia in Alsace (France) over a year, to estimate the associated economic burden and to identify causes. Method A retrospective analysis was performed using data extracted from hospital databases. Costs were calculated from French official tariffs. Setting 31 public and private hospitals. A review of the medical records of patients with iatrogenic hypoglycemia-related hospital admissions was performed at the University Hospital of Strasbourg. Main outcome measures Hypoglycemia-related hospital admissions: number, costs and causes. Results Out of 42,381 hospitalizations, 147 iatrogenic hypoglycemia-related hospital admissions (0.4%) were identified; 41 patients with type 1 diabetes mellitus and 106 with type 2. The total cost associated to the 147 events was € 407,441. The median cost per patient was € 1,224.6 [563.0-2,505.7 (interquartile range)] for type 1 diabetes mellitus and € 3,670.9 [2,505.7-3,670.9] for type 2. Forty-six patients over the 147 were coming from the University Hospital of Strasbourg. In this hospital, the most common origin of the hypoglycemia was missed meals (n = 7), the second was a mismatch between antidiabetic medicines and carbohydrate intake (n = 6), the third was an incorrect use of antidiabetic medicines (n = 5). Conclusions 147 hospitalizations due to iatrogenic hypoglycemia were identified with an estimated global cost of € 407,441. Optimizing therapy with low-risk hypoglycemic medicines, improving access to continuous glucose monitoring systems and offering adequate education, could help address the causes of hypoglycemia.

Remote Monitoring of Diabetes: A Cloud-Connected Digital System for Individuals With Diabetes and Their Health Care Providers.

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.

Closed-loop insulin delivery in adults with type 1 diabetes in real-life conditions: a 12-week multicentre, open-label randomised controlled crossover trial.

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<0·0001). Five severe hypoglycaemic episodes occurred in the DBLG1 group and three episodes occurred in the sensor-assisted pump therapy group, which were associated with hardware malfunctions or human error. INTERPRETATION: The DBLG1 system improves glucose control compared with sensor-assisted insulin pumps. This finding supports the use of closed-loop technology combined with appropriate health care organisation in adults with type 1 diabetes. FUNDING: French Innovation Fund, Diabeloop.

Treatment of NASH with Antioxidant Therapy: Beneficial Effect of Red Cabbage on Type 2 Diabetic Rats.

AIMS: Oxidative stress (OS) plays a major role in type 2 diabetes and its vascular and hepatic complications, and novel therapeutic approaches include natural antioxidants. Our previous chemical and biological studies demonstrated the antioxidant activities of red cabbage (RC), and here, we aimed to determine the in vivo effects of 2-month long RC consumption using a high-fat/high-fructose model of diabetic rats. RESULTS: This vegetable, associated with lifestyle measurement, was shown to decrease OS and increase vascular endothelial NO synthase expression, ensuring vascular homeostasis. In the liver, RC consumption decreased OS by inhibiting p22phox expression and Nrf2 degradation and increasing catalase activity. It inhibited the activation of SREBP (1c, 2), ChREBP, NF-κB, ERK1/2, PPARγ, and GS and SIRT1 decrease, as observed in diabetic rats. CONCLUSION/INNOVATION: RC consumption led to metabolic profile improvement, together with hepatic function improvements. Although lifestyle changes are not sufficient to prevent diabetic complications, enrichment with RC avoids progression hepatic complications. This antioxidant strategy using RC does not only able to increase antioxidant defense, such as classical antioxidant, but also able to assure a metabolic and energetic balance to reverse complications. Whereas traditional medical therapy failed to reverse NASH in diabetic patients, consumption of RC should be a natural therapy to treat it.

Beneficial effects of cherry consumption as a dietary intervention for metabolic, hepatic and vascular complications in type 2 diabetic rats.

BACKGROUND: Oxidative stress (OS) plays an important role in type 2 diabetes (T2D) pathogenesis and its complications. New therapies target natural antioxidants as an alternative and/or supplemental strategy to prevent and control them. Our previous chemical and biological studies highlighted the important antioxidant activities of cherries, among other fruits and vegetables, thus we aimed to determine in vivo effects of 2-month long cherry consumption using a high-fat/high-fructose (HFHF) model of diabetic-rats (Lozano et al. in Nutr Metab 13:15, 2016). METHODS: After 2 months of HFHF, male Wistar rats were divided into: HFHF and HFHF enriched in cherry (nutritional approach) or standard diet ND (lifestyle measures) and ND plus cherry during 2 months. Metabolic, lipidic, oxidative parameters were quantified. Tissues (liver, pancreas and vessels) OS were assessed and hepatic (steatosis, fibrosis, inflammation) and vascular (endothelial dysfunction) complications were characterized. RESULTS: T2D was induced after 2 months of HFHF diet, characterized by systemic hyperglycaemia, hyperinsulinemia, glucose intolerance, dyslipidaemia, hyperleptinemia, and oxidative stress associated with endothelial dysfunction and hepatic complications. Cherry consumption for 2 months, in addition to lifestyle measures, in T2D-rats decreased and normalized the systemic disturbances, including oxidative stress complications. Moreover, in the vessel, cherry consumption decreased oxidative stress and increased endothelial nitric oxide (NO) synthase levels, thus increasing NO bioavailability, ensuring vascular homeostasis. In the liver, cherry consumption decreased oxidative stress by inhibiting NADPH oxidase subunit p22phox expression, nuclear factor erythroid-2 related factor 2 (Nrf2) degradation and the formation of reactive oxygen species. It inhibited the activation of sterol regulatory element-binding proteins (1c and 2) and carbohydrate-responsive element-binding protein, and thus decreased steatosis as observed in T2D rats. This led to the improvement of metabolic profiles, together with endothelial and hepatic function improvements. CONCLUSION: Cherry consumption normalized vascular function and controlled hepatic complications, thus reduced the risk of diabetic metabolic disorders. These results demonstrate that a nutritional intervention with a focus on OS could prevent and/or delay the onset of vascular and hepatic complications related to T2D.