Beneficial effects of automated insulin delivery over one-year follow-up in real life for youths and adults with type 1 diabetes irrespective of patient characteristics.

AIM: To investigate glycaemic outcomes in youths and adults with type 1 diabetes with either MiniMed™ 780G or Tandem t:slim X2™ control-IQ automated insulin delivery (AID) systems and to evaluate clinical factors that migrate, mitigate the achievement of therapeutic goals. MATERIALS AND METHODS: This retrospective, real-world, observational study was conducted in a specialized university type 1 diabetes centre with patients observed for 3-12 months post-initiation of an AID system. Primary outcomes were the percentage time in the target glucose range [TIR70-180 mg/dl (3.9-10 mmol/L)] as measured by continuous glucose monitoring, mean glucose management indicator (GMI) and glycated haemoglobin (HbA1c) levels. RESULTS: Our study cohort consisted of 48 adolescents and 183 adults (55% females) aged 10-77 years. The mean (95% confidence interval) TIR70-180 mg/dl after 30 days was higher than baseline and by 14% points after 360 days with 71.33% (69.4-73.2) (n = 123, p < .001). HbA1c levels decreased by 0.7% and GMI by 0.6% after 360 days. The proportion of time spent <70 mg/dl (3.9 mmol/L) was not significantly different from baseline. During follow-up, 780G users had better continuous glucose monitoring results than control-IQ users but similar HbA1c levels, and an increased risk of weight gain. Age at onset influenced TIR70-180 mg/dl in univariate analysis but there was no significant relationship after adjusting on explanatory variables. Baseline body mass index did not influence the performance of AID systems. CONCLUSIONS: This analysis showed the beneficial effects of two AID systems for people with type 1 diabetes across a broad spectrum of participant characteristics. Only half of the participants achieved international recommendations for glucose control with TIR70-180 mg/dl >70%, HbA1c levels or GMI <7%, which outlines the need to maintain strong educational and individual strategies.

Human Pancreatic Islets React to Glucolipotoxicity by Secreting Pyruvate and Citrate.

Progressive decline in pancreatic beta-cell function is central to the pathogenesis of type 2 diabetes (T2D). Here, we explore the relationship between the beta cell and its nutritional environment, asking how an excess of energy substrate leads to altered energy production and subsequent insulin secretion. Alterations in intracellular metabolic homeostasis are key markers of islets with T2D, but changes in cellular metabolite exchanges with their environment remain unknown. We answered this question using nuclear magnetic resonance-based quantitative metabolomics and evaluated the consumption or secretion of 31 extracellular metabolites from healthy and T2D human islets. Islets were also cultured under high levels of glucose and/or palmitate to induce gluco-, lipo-, and glucolipotoxicity. Biochemical analyses revealed drastic alterations in the pyruvate and citrate pathways, which appear to be associated with mitochondrial oxoglutarate dehydrogenase (OGDH) downregulation. We repeated these manipulations on the rat insulinoma-derived beta-pancreatic cell line (INS-1E). Our results highlight an OGDH downregulation with a clear effect on the pyruvate and citrate pathways. However, citrate is directed to lipogenesis in the INS-1E cells instead of being secreted as in human islets. Our results demonstrate the ability of metabolomic approaches performed on culture media to easily discriminate T2D from healthy and functional islets.

Twelve-month results of the ADAPT randomized controlled trial: Reproducibility and sustainability of advanced hybrid closed-loop therapy outcomes versus conventional therapy in adults with type 1 diabetes.

AIMS: To reassess the 6-month efficacy and to assess the 12-month sustained efficacy of the MiniMed™ 780G advanced hybrid closed-loop automated insulin delivery (AID) system compared to multiple daily injections plus intermittently scanned glucose monitoring (MDI+isCGM) in people with type 1 diabetes not meeting glucose targets. METHODS: The ADAPT study was a prospective, multicentre, open-label, randomized control trial in people with type 1 diabetes, with a glycated haemoglobin (HbA1c) concentration of at least 8.0% (64 mmol/mol), on MDI+isCGM therapy. After a 6-month study phase, participants randomized at baseline to MDI+isCGM switched to AID (SWITCH) while the others continued AID therapy (SUSTAIN) for an additional 6 months. The primary endpoint of this continuation phase was the within-group change in mean HbA1c between 6 and 12 months, with superiority in the SWITCH group and noninferiority in the SUSTAIN group (ClinicalTrials.gov: NCT04235504). RESULTS: A total of 39 SWITCH and 36 SUSTAIN participants entered the continuation phase. In the SWITCH group, HbA1c was significantly decreased by -1.4% (95% confidence interval [CI] -1.7% to -1.1%; P < 0.001) from a mean ± SD of 8.9% ± 0.8% (73.9 ± 8.6 mmol/mol) at 6 months to 7.5% ± 0.6% (58.5 ± 6.9 mmol/mol) at 12 months. Mean HbA1c increased by 0.1% (95% CI -0.05% to +0.25%), from 7.3% ± 0.6% (56.5 ± 6.7 mmol/mol) to 7.4% ± 0.8% (57.7 ± 9.1 mmol/mol) in the SUSTAIN group, meeting noninferiority criteria. Three severe hypoglycaemia events occurred in two SWITCH participants during the continuation phase. CONCLUSION: ADAPT study phase glycaemic improvements were reproduced and sustained in the continuation phase, supporting the early adoption of AID therapy in people with type 1 diabetes not meeting glucose targets on MDI therapy.

Performance and patients' satisfaction with the A7+TouchCare insulin patch pump system: A randomized controlled non-inferiority study.

BACKGROUND: We assessed the performance and patient satisfaction of a new insulin patch pump, the A7+TouchCare (Medtrum), compared with the Omnipod system. METHODS: This multicenter, randomized, open-label, controlled study enrolled 100 adult patients with type 1 or type 2 diabetes mellitus (A1C ≥ 6.5% and ≤ 9.5%, i.e., 48 to 80 mmol/mol) who were assigned with the Omnipod or with the A7+TouchCare pump for 3 months. The primary study outcome was the glucose management indicator (GMI) calculated with continuous glucose monitoring (CGM). RESULTS: Premature withdrawals occurs respectively in 2 and 9 participants in the Omnipod and TouchCare groups. In the Per Protocol analysis, the difference in GMI between groups was 0.002% (95% confidence interval -0.251; 0.255). The non-inferiority was demonstrated since the difference between treatments did not overlap the pre-defined non-inferiority margin (0.4%). There was no significant difference in CGM parameters between groups. On average, patients in both groups were satisfied/very satisfied with the insulin pump system. Patients preferred Omnipod as an insulin management system and especially the patch delivery system but preferred the A7+TouchCare personal diabetes manager to control the system. CONCLUSIONS: This study showed that the A7+TouchCare insulin pump was as efficient as the Omnipod pump in terms of performance and satisfaction. CLINICAL TRAIL REGISTRATION: The study was registered in the ClinicalTrials.gov protocol register (NCT04223973).

Advanced hybrid closed loop therapy versus conventional treatment in adults with type 1 diabetes (ADAPT): a randomised controlled study.

BACKGROUND: Adults with type 1 diabetes who are treated with multiple daily injections of insulin plus intermittently scanned continuous glucose monitoring (isCGM) can have suboptimal glucose control. We aimed to assess the efficacy of an advanced hybrid closed loop (AHCL) system compared with such therapy in this population. METHODS: The Advanced Hybrid Closed Loop Study in Adult Population with Type 1 Diabetes (ADAPT) trial is a prospective, multicentre, open-label, randomised controlled trial that involved 14 centres in three European countries (France, Germany, and the UK). We enrolled patients who were at least 18 years of age, had a type 1 diabetes duration of at least 2 years, HbA1c of at least 8% (64 mmol/mol), and were using multiple daily injections of insulin plus isCGM (cohort A) or real time continuous glucose monitoring (cohort B) for at least 3 months. Here, only results for cohort A are reported. Participants were randomly allocated 1:1 to AHCL therapy or continuation of multiple daily injections of insulin plus continuous glucose monitoring for 6 months with an investigator-blinded block randomisation procedure. Participants and treating clinicians could not be masked to the arm assignment. The primary endpoint was the between-group difference in mean HbA1c change from baseline to 6 months in the intention-to-treat population using AHCL therapy and those using multiple daily injections of insulin plus isCGM. The primary endpoint was analysed using a repeated measures random-effects model with the study arm and period as factors. Safety endpoints included the number of device deficiencies, severe hypoglycaemic events, diabetic ketoacidosis, and serious adverse events. This study is registered with ClinicalTrials.gov, NCT04235504. FINDINGS: Between July 13, 2020, and March 12, 2021, 105 people were screened and 82 randomly assigned to treatment (41 in each arm). At 6 months, mean HbA1c had decreased by 1·54% (SD 0·73), from 9·00% to 7·32% in the AHCL group and 0·20% (0·80) in the multiple daily injections of insulin plus isCGM from 9·07% to 8·91% (model-based difference -1·42%, 95% CI -1·74 to -1·10; p<0·0001). No diabetic ketoacidosis, severe hypoglycaemia, or serious adverse events related to study devices occurred in either group; two severe hypoglycaemic events occurred in the run-in phase. 15 device-related non-serious adverse events occurred in the AHCL group, compared with three in the multiple daily injections of insulin plus isCGM group. Two serious adverse events occurred (one in each group), these were breast cancer (in one patient in the AHCL group) and intravitreous haemorrhage (in one patient in the multiple daily injections of insulin plus isCGM group). INTERPRETATION: In people with type 1 diabetes using multiple daily injections of insulin plus isCGM and with HbA1c of at least 8%, the use of AHCL confers benefits in terms of glycaemic control beyond those that can be achieved with multiple daily injections of insulin plus isCGM. These data support wider access to AHCL in people with type 1 diabetes not at target glucose levels. FUNDING: Medtronic International Trading Sàrl.

Impact of diabetes on COVID-19 prognosis beyond comorbidity burden: the CORONADO initiative.

AIMS/HYPOTHESIS: Diabetes has been recognised as a pejorative prognostic factor in coronavirus disease 2019 (COVID-19). Since diabetes is typically a disease of advanced age, it remains unclear whether diabetes remains a COVID-19 risk factor beyond advanced age and associated comorbidities. We designed a cohort study that considered age and comorbidities to address this question. METHODS: The Coronavirus SARS-CoV-2 and Diabetes Outcomes (CORONADO) initiative is a French, multicentric, cohort study of individuals with (exposed) and without diabetes (non-exposed) admitted to hospital with COVID-19, with a 1:1 matching on sex, age (±5 years), centre and admission date (10 March 2020 to 10 April 2020). Comorbidity burden was assessed by calculating the updated Charlson comorbidity index (uCCi). A predefined composite primary endpoint combining death and/or invasive mechanical ventilation (IMV), as well as these two components separately, was assessed within 7 and 28 days following hospital admission. We performed multivariable analyses to compare clinical outcomes between patients with and without diabetes. RESULTS: A total of 2210 pairs of participants (diabetes/no-diabetes) were matched on age (mean±SD 69.4±13.2/69.5±13.2 years) and sex (36.3% women). The uCCi was higher in individuals with diabetes. In unadjusted analysis, the primary composite endpoint occurred more frequently in the diabetes group by day 7 (29.0% vs 21.6% in the no-diabetes group; HR 1.43 [95% CI 1.19, 1.72], p<0.001). After multiple adjustments for age, BMI, uCCi, clinical (time between onset of COVID-19 symptoms and dyspnoea) and biological variables (eGFR, aspartate aminotransferase, white cell count, platelet count, C-reactive protein) on admission to hospital, diabetes remained associated with a higher risk of primary composite endpoint within 7 days (adjusted HR 1.42 [95% CI 1.17, 1.72], p<0.001) and 28 days (adjusted HR 1.30 [95% CI 1.09, 1.55], p=0.003), compared with individuals without diabetes. Using the same adjustment model, diabetes was associated with the risk of IMV, but not with risk of death, within 28 days of admission to hospital. CONCLUSIONS/INTERPRETATION: Our results demonstrate that diabetes status was associated with a deleterious COVID-19 prognosis irrespective of age and comorbidity status. TRIAL REGISTRATION: ClinicalTrials.gov NCT04324736.

Cost-Effectiveness Evaluation of a Remote Monitoring Programme Including Lifestyle Education Software in Type 2 Diabetes: Results of the Educ@dom Study.

INTRODUCTION: Telemedicine programs using health technological innovation to remotely monitor the lifestyles of patients with type 2 diabetes (T2D) can improve glycaemic control and thus reduce the incidence of complications as well as management costs. In this context, an assessment was made of the 1-year and 2-year cost-effectiveness of the EDUC@DOM telemonitoring and tele-education program. METHODS: The EDUC@DOM study was a multicentre randomized controlled trial conducted between 2013 and 2017 that compared a telemonitoring group (TMG) to a control group (CG) merged with health insurance databases to extract economic data on resource consumption. Economic analysis was performed from the payer perspective, and direct costs and indirect costs were considered. The clinical outcome used was the intergroup change in glycated haemoglobin (HbA1c) levels from baseline. Missing economic data were imputed using multiple imputation, and fitted values from a generalized linear mixed model were used to calculate the incremental cost-effectiveness ratio (ICER). Bootstrapped 95% confidence ellipses were drawn in the cost-effectiveness plan. RESULTS: The main analysis included data from 256 patients: 126 in the TMG and 130 in the CG. Incremental costs over 1 and 2 years were equal to €2129 and €5101, respectively, in favour of the TMG. Once imputed and adjusted for confounding factors, the TMG trends to a 21% cost decrease over 1 and 2 years of follow-up (0.79 [0.58; 1.08], p = 0.1452 and 0.79 [0.61; 1.03], p = 0.0879, respectively). The EDUC@DOM program led to a €1334 cost saving and a 0.17 decrease in HbA1c over 1 year and a €3144 cost saving and a 0.14 decrease in HbA1c over 2 years. According to the confidence ellipse, EDUC@DOM was a cost-effective strategy. CONCLUSION: This study provides additional economic information on telemonitoring and tele-education programs to enhance their acceptance and promote their use. In the light of this work, the EDUC@DOM program is a cost-saving strategy in T2D management. TRIAL REGISTRATION: This trial was registered in the Clinical Trials Database on 27 September 2013 under no. NCT01955031 and bears ID-RCB no. 2013-A00391-44.

History of bariatric surgery and COVID-19 outcomes in patients with type 2 diabetes: Results from the CORONADO study.

OBJECTIVE: This study assessed the impact of a history of metabolic and bariatric surgery (MBS) on the clinical outcomes in patients with type 2 diabetes (T2D) and severe obesity hospitalized for COVID-19. METHODS: In this post hoc analysis from the nationwide observational CORONADO (Coronavirus SARS-CoV2 and Diabetes Outcomes) study, patients with T2D and a history of MBS were matched with patients without MBS for age, sex, and BMI either at the time of MBS or on admission for COVID-19. The composite primary outcome (CPO) combined invasive mechanical ventilation and/or death within 7 and 28 days following admission. RESULTS: Out of 2,398 CORONADO participants, 20 had a history of MBS. When matching for BMI at the time of MBS and after adjustment for diabetes duration, the CPO occurred less frequently within 7 days (3 vs. 17 events, OR: 0.15 [0.01 to 0.94], p = 0.03) and 28 days (3 vs. 19 events, OR: 0.11 [0.01 to 0.71], p = 0.02) in patients with MBS (n = 16) vs. controls (n = 44). There was no difference in CPO rate between patients with MBS and controls when matching for BMI on admission. CONCLUSIONS: These data are reassuring regarding COVID-19 prognosis in patients with diabetes and a history of MBS compared with those without MBS.

Impact of a Remote Monitoring Programme Including Lifestyle Education Software in Type 2 Diabetes: Results of the Educ@dom Randomised Multicentre Study.

INTRODUCTION: Telemonitoring in type 2 diabetes (T2D) is mainly based on glucose monitoring. A new type of connected device which routinely gathers data on weight, physical activity and food intake could improve patients' diabetes control. The main aim of this study was to assess the efficacy of an at-home interventional programme incorporating such devices and lifestyle education software on diabetes control, i.e., change in HbA1c, compared to standard care. METHODS: This multicentre study randomly assigned 282 people with T2D to either a telemonitoring group (TMG) or a control group (CG) for a 1-year intervention period. While routine follow-up was maintained in the CG, TMG subjects were provided with interactive lifestyle educational software (with artificial intelligence algorithms) and connected objects (blood glucose meters, scales and actimeters) for use in their own homes and were remotely monitored by their diabetologists. Changes in HbA1c were compared between groups using a mixed linear model. RESULTS: The mean HbA1c dropped from 7.8 ± 0.8% (62 mmol/mol) to 7.4 ± 1.0% (57 mmol/mol) in the TMG and from 7.8 ± 0.8% (62 mmol/mol) to 7.6 ± 1.0% (60 mmol/mol) in the CG, resulting in an intergroup difference of - 0.16 (p = 0.06) in favour of TMG, after adjustment for confounding factors. Within TMG, the decrease in HbA1c was greater in frequent users: - 0.23% (p = 0.03) in the case of connections to telemonitoring synthesis above the median and - 0.21% (p = 0.05) in the case of connections to tele-education software above the median compared to the CG. Significant weight loss was observed in the TMG but only in women (p = 0.01). FINDINGS: The EDUC@DOM telemonitoring and tele-education device did not highlight a significant decrease in HbA1c levels compared to routine management although a slight, albeit significant improvement in glycaemic control was observed in the frequent user subgroup as well as significant weight loss but only in women. A high level of satisfaction with the connected device was recorded amongst all participants. TRIAL REGISTRATION: This trial was registered in the Clinical Trials Database on September 27, 2013, under no. NCT01955031 and bears ID-RCB number 2013-A00391-44.

Ten-year outcomes of islet transplantation in patients with type 1 diabetes: Data from the Swiss-French GRAGIL network.

To describe the 10-year outcomes of islet transplantation within the Swiss-French GRAGIL Network, in patients with type 1 diabetes experiencing high glucose variability associated with severe hypoglycemia and/or with functional kidney graft. We conducted a retrospective analysis of all subjects transplanted in the GRAGIL-1c and GARGIL-2 islet transplantation trials and analyzed components of metabolic control, graft function and safety outcomes over the 10-year period of follow-up. Forty-four patients were included between September 2003 and April 2010. Thirty-one patients completed a 10-year follow-up. Ten years after islet transplantation, median HbA1c was 7.2% (6.2-8.0) (55 mmol/mol [44-64]) versus 8.0% (7.1-9.1) (64 mmol/mol [54-76]) before transplantation (p < .001). Seventeen of 23 (73.9%) recipients were free of severe hypoglycemia, 1/21 patients (4.8%) was insulin-independent and median C-peptide was 0.6 ng/ml (0.2-1.2). Insulin requirements (UI/kg/day) were 0.3 (0.1-0.5) versus 0.5 (0.4-0.6) before transplantation (p < .001). Median (IQR) ß-score was 1 (0-4) (p < .05 when comparing with pre-transplantation values) and 51.9% recipients had a functional islet graft at 10 years. With a 10-year follow-up in a multicentric network, islet transplantation provided sustained improvement of glycemic control and was efficient to prevent severe hypoglycemia in almost 75% of the recipients.

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.

Phenotypic characteristics and prognosis of newly diagnosed diabetes in hospitalized patients with COVID-19: Results from the CORONADO study.

In patients with diabetes hospitalized for COVID-19 in CORONADO study, 2.8% had a newly discovered. 2.8% had a newly discovered diabetes (NDD): mean age 60.2 ± 12.5 years and HbA1C 9.0 ± 2.5%. When compared with center, age and sex-matched patients with established type 2 diabetes, NDD was not significantly associated with a more severe COVID-19 prognosis.

Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19.

AIMS: Metformin exerts anti-inflammatory and immunosuppressive effects. We addressed the impact of prior metformin use on prognosis in patients with type 2 diabetes hospitalised for COVID-19. METHODS: CORONADO is a nationwide observational study that included patients with diabetes hospitalised for COVID-19 between March 10 and April 10, 2020 in 68 French centres. The primary outcome combined tracheal intubation and/or death within 7 days of admission. A Kaplan-Meier survival curve was reported for death up to day 28. The association between metformin use and outcomes was then estimated in a logistic regression analysis after applying a propensity score inverse probability of treatment weighting approach. RESULTS: Among the 2449 patients included, 1496 were metformin users and 953 were not. Compared with non-users, metformin users were younger with a lower prevalence of diabetic complications, but had more severe features of COVID-19 on admission. The primary endpoint occurred in 28.0% of metformin users (vs 29.0% in non-users, P = 0.6134) on day 7 and in 32.6% (vs 38.7%, P = 0.0023) on day 28. The mortality rate was lower in metformin users on day 7 (8.2 vs 16.1%, P < 0.0001) and on day 28 (16.0 vs 28.6%, P < 0.0001). After propensity score weighting was applied, the odds ratios for primary outcome and death (OR [95%CI], metformin users vs non-users) were 0.838 [0.649-1.082] and 0.688 [0.470-1.007] on day 7, then 0.783 [0.615-0.996] and 0.710 [0.537-0.938] on day 28, respectively. CONCLUSION: Metformin use appeared to be associated with a lower risk of death in patients with diabetes hospitalised for COVID-19.