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.

Associations of clinical, psychological, and sociodemographic characteristics and ecological momentary assessment completion in the 10-week Hypo-METRICS study: Hypoglycaemia MEasurements ThResholds and ImpaCtS.

INTRODUCTION: Reporting of hypoglycaemia and its impact in clinical studies is often retrospective and subject to recall bias. We developed the Hypo-METRICS app to measure the daily physical, psychological, and social impact of hypoglycaemia in adults with type 1 and insulin-treated type 2 diabetes in real-time using ecological momentary assessment (EMA). To help assess its utility, we aimed to determine Hypo-METRICS app completion rates and factors associated with completion. METHODS: Adults with diabetes recruited into the Hypo-METRICS study were given validated patient-reported outcome measures (PROMs) at baseline. Over 10 weeks, they wore a blinded continuous glucose monitor (CGM), and were asked to complete three daily EMAs about hypoglycaemia and aspects of daily functioning, and two weekly sleep and productivity PROMs on the bespoke Hypo-METRICS app. We conducted linear regression to determine factors associated with app engagement, assessed by EMA and PROM completion rates and CGM metrics. RESULTS: In 602 participants (55% men; 54% type 2 diabetes; median(IQR) age 56 (45-66) years; diabetes duration 19 (11-27) years; HbA1c 57 (51-65) mmol/mol), median(IQR) overall app completion rate was 91 (84-96)%, ranging from 90 (81-96)%, 89 (80-94)% and 94(87-97)% for morning, afternoon and evening check-ins, respectively. Older age, routine CGM use, greater time below 3.0 mmol/L, and active sensor time were positively associated with app completion. DISCUSSION: High app completion across all app domains and participant characteristics indicates the Hypo-METRICS app is an acceptable research tool for collecting detailed data on hypoglycaemia frequency and impact in real-time.

Effects of hypoglycaemic agents on reducing surrogate metabolic parameters for the prevention of cardiovascular events and death in patients with type 2 diabetes: A systematic review and meta-analysis.

AIMS: To investigate the impact of glucose-lowering therapy-induced glycated haemoglobin (HbA1c) reduction on the risk of major clinical events according to body weight change and, as a secondary objective, to evaluate the impact of concomitant reductions in HbA1c and body weight on major clinical events. MATERIALS AND METHODS: We searched the MEDLINE and EMBASE databases up to June 30, 2022, for large-scale studies on glucose-lowering therapies in which more than 1000 patient-years of follow-up in each randomized group were completed. The primary outcome was all-cause mortality. The study was registered in PROSPERO (CRD42022355479). RESULTS: Thirty-four trials involving 227 220 patients with type 2 diabetes were meta-analysed using a random-effects model. Each 1% reduction in HbA1c was associated with a different risk of mortality depending on the ability of glucose-lowering therapies to induce body weight loss or gain. When glucose-lowering therapies were associated with weight gain, the risk of mortality increased by 8% (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.00-1.16) for each 1% reduction in HbA1c. When glucose-lowering therapies were associated with weight loss, the risk of mortality was reduced by 22% (HR 0.78, 95% CI 0.72-0.85) for each 1% reduction in HbA1c. In addition, concomitant reductions in HbA1c and body weight were associated with a significantly lower risk of mortality and vascular events. CONCLUSIONS: In patients with type 2 diabetes, concomitant reductions in HbA1c and body weight might be more effective in preventing the risk of vascular events and mortality.

Should people with type 2 diabetes treated by multiple daily insulin injections with home health care support be switched to hybrid closed-loop? The CLOSE AP+ randomized controlled trial.

AIM: The study aim was to evaluate the feasibility, safety and efficacy of automated insulin delivery (AID) assisted by home health care (HHC) services in people with type 2 diabetes unable to manage multiple daily insulin injections (MDI) at home on their own. PATIENTS AND METHODS: This was an open label, multicentre, randomized, parallel group trial. In total, 30 adults with type 2 diabetes using MDI and requiring nursing support were randomly allocated to AID or kept their usual therapy over a 12-week period. Both treatments were managed with the support of HHC services. The primary outcome was the percentage time in the target glucose range of 70-180 mg/dl (TIR). Secondary outcomes included other continuous glucose monitoring metrics, glycated haemoglobin (HbA1c) levels, daily insulin doses, body weight, and of quality of life scores, fear of hypoglycaemia and satisfaction questionnaires. RESULTS: Age (69.7 vs. 69.3 years) and HbA1c (9.25 vs. 9.0) did not differ in MDI and AID at baseline. Compared with MDI, AID resulted in a significant increase in TIR by 27.4% [95% CI (15.0-39.8); p < .001], a decrease in time above range by 27.7% and an unchanged time below range of <1%. A between-group difference in HbA1c was 1.3% favouring AID. Neither severe hypoglycaemia nor ketoacidosis occurred in either group. Patient and caregiver satisfaction with AID was high. CONCLUSIONS: AID combined with tailored HHC services significantly improved glycaemic control with no safety issues in people with type 2 diabetes previously under an MDI regimen with HHC. AID should be considered a safe option in these people when lacking acceptable glucose control.

Continuous glucose monitoring-based time-in-range using insulin glargine 300 units/ml versus insulin degludec 100 units/ml in type 1 diabetes: The head-to-head randomized controlled InRange trial.

AIM: To use continuous glucose monitoring (CGM)-based time-in-range (TIR) as a primary efficacy endpoint to compare the second-generation basal insulin (BI) analogues insulin glargine 300 U/ml (Gla-300) and insulin degludec 100 U/ml (IDeg-100) in adults with type 1 diabetes (T1D). MATERIALS AND METHODS: InRange was a 12-week, multicentre, randomized, active-controlled, parallel-group, open-label study comparing glucose TIR and variability between Gla-300 and IDeg-100 using blinded 20-day CGM profiles. The inclusion criteria consisted of adults with T1D treated with multiple daily injections, using BI once daily and rapid-acting insulin analogues for at least 1 year, with an HbA1c of 7% or higher and of 10% or less at screening. RESULTS: Overall, 343 participants were randomized: 172 received Gla-300 and 171 IDeg-100. Non-inferiority (10% relative margin) of Gla-300 versus IDeg-100 was shown for the primary endpoint (percentage TIR ≥ 70 to ≤ 180 mg/dl): least squares (LS) mean (95% confidence interval) 52.74% (51.06%, 54.42%) for Gla-300 and 55.09% (53.34%, 56.84%) for IDeg-100; LS mean difference (non-inferiority): 3.16% (0.88%, 5.44%) (non-inferiority P = .0067). Non-inferiority was shown on glucose total coefficient of variation (main secondary endpoint): LS mean 39.91% (39.20%, 40.61%) and 41.22% (40.49%, 41.95%), respectively; LS mean difference (non-inferiority) -5.44% (-6.50%, -4.38%) (non-inferiority P < .0001). Superiority of Gla-300 over IDeg-100 was not shown on TIR. Occurrences of self-measured and CGM-derived hypoglycaemia were comparable between treatment groups. Safety profiles were consistent with known profiles, with no unexpected findings. CONCLUSIONS: Using clinically relevant CGM metrics, InRange shows that Gla-300 is non-inferior to IDeg-100 in people with T1D, with comparable hypoglycaemia and safety profiles.

Trends of glucose, lactate and ketones during anaerobic and aerobic exercise in subjects with type 1 diabetes: The ACTION-1 study.

BACKGROUND: Exercise is part of type 1 diabetes (T1D) management due to its cardiovascular and metabolic benefits. However, despite using continuous glucose monitoring, many patients are reluctant to exercise because of fear for hypoglycaemia. AIMS: We assessed trends in glucose, lactate and ketones during anaerobic and aerobic exercise in people with T1D and compared incremental area under the curve (AUC) between both exercises. METHODS: Twenty-one men with T1D (median [IQR]: age 29 years [28-38], body mass index (BMI) 24.4 kg/m2 [22.3-24.9], HbA1c 7.2% [6.7-7.8]), completed a cardiopulmonary exercise test (CPET) and a 60-min aerobic exercise (AEX) at 60% VO2 peak on an ergometer bicycle within a 6-week period. Subjects consumed a standardised breakfast (6 kcal/kg, 20.2 g CHO/100 ml) before exercise without pre-meal insulin and basal insulin for pump users. RESULTS: During CPET, glucose levels increased, peaking at 331 mg/dl [257-392] 1-3 h after exercise and reaching a nadir 6 h after exercise at 176 mg/dl [118-217]. Lactate levels peaked at 6.0 mmol/L [5.0-6.6] (max 13.5 mmol/L). During AEX, glucose levels also increased, peaking at 305 mg/dl [245-336] 80 min after exercise and reaching a nadir 6 h after exercise at 211 mg/dl [116-222]. Lactate levels rose quickly to a median of 4.3 mmol/L [2.7-6.7] after 10 min. Ketone levels were low during both tests (median ≤ 0.2 mmol/L). Lactate, but not glucose or ketone AUC, was significantly higher in CPET compared to AEX (p = 0.04). CONCLUSIONS: Omitting pre-meal insulin and also basal insulin in pump users, did prevent hypoglycaemia but induced hyperglycaemia due to a too high carbohydrate ingestion. No ketosis was recorded during or after the exercises. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT05097339.

Hypo-METRICS: Hypoglycaemia-MEasurement, ThResholds and ImpaCtS-A multi-country clinical study to define the optimal threshold and duration of sensor-detected hypoglycaemia that impact the experience of hypoglycaemia, quality of life and health economic outcomes: The study protocol.

INTRODUCTION: Hypoglycaemia is a significant burden to people living with diabetes and an impediment to achieving optimal glycaemic outcomes. The use of continuous glucose monitoring (CGM) has improved the capacity to assess duration and level of hypoglycaemia. The personal impact of sensor-detected hypoglycaemia (SDH) is unclear. Hypo-METRICS is an observational study designed to define the threshold and duration of sensor glucose that provides the optimal sensitivity and specificity for events that people living with diabetes experience as hypoglycaemia. METHODS: We will recruit 600 participants: 350 with insulin-treated type 2 diabetes, 200 with type 1 diabetes and awareness of hypoglycaemia and 50 with type 1 diabetes and impaired awareness of hypoglycaemia who have recent experience of hypoglycaemia. Participants will wear a blinded CGM device and an actigraphy monitor to differentiate awake and sleep times for 10 weeks. Participants will be asked to complete three short surveys each day using a bespoke mobile phone app, a technique known as ecological momentary assessment. Participants will also record all episodes of self-detected hypoglycaemia on the mobile app. We will use particle Markov chain Monte Carlo optimization to identify the optimal threshold and duration of SDH that have optimum sensitivity and specificity for detecting patient-reported hypoglycaemia. Key secondary objectives include measuring the impact of symptomatic and asymptomatic SDH on daily functioning and health economic outcomes. ETHICS AND DISSEMINATION: The protocol was approved by local ethical boards in all participating centres. Study results will be shared with participants, in peer-reviewed journal publications and conference presentations.

Reduction of clinically important low glucose excursions with a long-term implantable continuous glucose monitoring system in adults with type 1 diabetes prone to hypoglycaemia: the France Adoption Randomized Clinical Trial.

AIM: To assess the glucose control outcomes of the implantable Eversense real-time continuous glucose monitoring (CGM) system compared to self-monitoring of blood glucose or intermittently scanned CGM in patients with type 1 (T1D) or type 2 diabetes (T2D). PATIENTS AND METHODS: This was a randomized (2:1), prospective, national, multicentre study. All participants, aged >18 years and on multiple daily insulin injections or insulin pump treatment, had a sensor inserted, which was activated only in the "enabled" group. Included patients had T1D or T2D with a glycated haemoglobin (HbA1c) level > 8% (64 mmol/mol) (Cohort 1) or T1D with a time spent with glucose values below 70 mg/dL (3.8 mmol/l) (TBR<70 ) for >1.5 h/d during the previous 28 days (Cohort 2). The primary outcomes were HbA1c change at D180 (Cohort 1) or change in time spent with glucose values below 54 mg/dL (TBR<54 ) during the period of Day (D)90 to D120 (Cohort 2). A covariance model (analyses of covariance) was used for endpoint analyses. RESULTS: Overall, 149 patients were included in Cohort 1 and 90 in Cohort 2. In Cohort 1, the adjusted mean difference (enabled - control) in HbA1c at D180 was -0.1% (95% confidence interval [CI] -0.4; 0.1; P = 0.341). No significant difference in time with values in the range 70 to 180 mg/dL or time with values above range (>180 mg/dL) was observed. In Cohort 2, the mean adjusted difference in TBR<54 was -1.6% (95% CI -3.1; -0.1; P = 0.039) during D90 to D120 and remained at -2.6% (95% CI -4.5; -0.6; P = 0.011) during D150 to D180 (prespecified secondary outcome). The CGM system was found to be safe. CONCLUSION: This study shows that the Eversense CGM system can significantly decrease TBR<54 in patients with T1D prone to hypoglycaemia.

Outcomes of hybrid closed-loop insulin delivery activated 24/7 versus evening and night in free-living prepubertal children with type 1 diabetes: A multicentre, randomized clinical trial.

AIM: To assess the safety and efficacy of hybrid closed-loop (HCL) insulin delivery 24/7 versus only evening and night (E/N), and on extended 24/7 use, in free-living children with type 1 diabetes. MATERIALS AND METHODS: Prepubertal children (n = 122; 49 females/73 males; age, 8.6 ± 1.6 years; diabetes duration, 5.2 ± 2.3 years; insulin pump use, 4.6 ± 2.5 years; HbA1c 7.7% ± 0.7%/61 ± 5 mmol/mol) from four centres were randomized for 24/7 versus E/N activation of the Tandem Control-IQ system for 18 weeks. Afterwards, all children used the activated system 24/7 for 18 more weeks. The primary outcome was the percentage of time spent in the 70-180 mg/dL glucose range (TIR). RESULTS: HCL was active 94.1% and 51.1% of the time in the 24/7 and E/N modes, respectively. TIR from baseline increased more in the 24/7 versus the E/N mode (52.9% ± 9.5% to 67.3% ± 5.6% [+14.4%, 95% CI 12.4%-16.7%] vs. 55.1% ± 10.8% to 64.7% ± 7.0% [+9.6%, 95% CI 7.4%-11.6%]; P = .001). Mean percentage time below range was similarly reduced, from 4.2% and 4.6% to 2.7%, and the mean percentage time above range decreased more in the 24/7 mode (41.9% to 30.0% [-11.9%, 95% CI 9.7%-14.6%] vs. 39.8% to 32.6% [-7.2%, 95% CI 5.0%-9.9%]; P = .007). TIR increased through the whole range of baseline levels and always more with 24/7 use. The results were maintained during the extension phase in those initially on 24/7 use and improved in those with initial E/N use up to those with 24/7 use. Neither ketoacidosis nor severe hypoglycaemia occurred. CONCLUSIONS: The current study shows the safety and efficacy of the Tandem Control-IQ system in free-living children with type 1 diabetes for both E/N and 24/7 use; 24/7 use shows better outcomes, sustained for up to 36 weeks with no safety issues.

Therapeutic indications and metabolic effects of metreleptin in patients with lipodystrophy syndromes: Real-life experience from a national reference network.

AIM: To describe baseline characteristics and follow-up data in patients with lipodystrophy syndromes treated with metreleptin in a national reference network, in a real-life setting. PATIENTS AND METHODS: Clinical and metabolic data from patients receiving metreleptin in France were retrospectively collected, at baseline, at 1 year and at the latest follow-up during treatment. RESULTS: Forty-seven patients with lipodystrophy including generalized lipodystrophy (GLD; n = 28) and partial lipodystrophy (PLD; n = 19) received metreleptin over the last decade. At baseline, the median (interquartile range [IQR]) patient age was 29.3 (16.6-47.6) years, body mass index was 23.8 (21.2-25.7) kg/m2 and serum leptin was 3.2 (1.0-4.9) ng/mL, 94% of patients had diabetes (66% insulin-treated), 53% had hypertension and 87% had dyslipidaemia. Metreleptin therapy, administered for a median (IQR) of 31.7 (14.2-76.0) months, was ongoing in 77% of patients at the latest follow-up. In patients with GLD, glycated haemoglobin (HbA1c) and fasting triglyceride levels significantly decreased from baseline to 1 year of metreleptin treatment, from 8.4 (6.5-9.9)% [68 (48-85) mmol/mol] to 6.8 (5.6-7.4)% [51(38-57) mmol/mol], and 3.6 (1.7-8.5) mmol/L to 2.2 (1.1-3.7) mmol/L, respectively (P < 0.001), with sustained efficacy thereafter. In patients with PLD, HbA1c was not significantly modified (7.7 [7.1-9.1]% [61 (54-76) mmol/mol] at baseline vs. 7.7 [7.4-9.5]% [61(57-80) mmol/mol] at 1 year), and the decrease in fasting triglycerides (from 3.3 [1.9-9.9] mmol/L to 2.5 [1.6-5.3] mmol/L; P < 0.01) was not confirmed at the latest assessment (5.2 [2.2-11.3] mmol/L). However, among PLD patients, at 1 year, 61% were responders regarding glucose homeostasis, with lower baseline leptin levels compared to nonresponders, and 61% were responders regarding triglyceridaemia. Liver enzymes significantly decreased only in the GLD group. CONCLUSIONS: In this real-life setting study, metabolic outcomes are improved by metreleptin therapy in patients with GLD. The therapeutic indication for metreleptin needs to be clarified in patients with PLD.

A specific association between laxative misuse and suicidal behaviours in patients with anorexia nervosa and bulimia nervosa.

OBJECTIVE: Eating disorders (ED) are associated with an in increased risk of suicidal behaviours. Laxative abuse might alter the gut-brain axis signaling, that might be implicated in the pathophysiology of suicide. This study aims to determine the association between laxative misuse and suicide attempt (SA) and suicidal ideation (SI) in patients with ED. METHODS: 277 patients with ED were recruited from an Eating Disorder Unit of Lapeyronie Academic Hospital, Montpellier, France. Sociodemographic and clinical data were collected. Chi-square and t test were used, with Bonferroni corrections where required. Multiple regression models assessed the relationships between laxative misuse, SA, and SI. RESULTS: 62 (22.4%) patients reported lifetime laxative misuse. They were more likely to have a history of SA than non-misusers [43.83 vs 19.9%, p < 0.001, odds ratio (OR) 3.68]. In the multivariate model, adjusted for other confounders, lifetime laxative misuse remained associated with SA (adjusted OR 3.79, p = 0.041). In past 28 days, patients with SA history reported misusing laxatives for more days than patients without SA history (6 vs 1.5 days, p = 0.01, adjusted for vomiting and ED severity). Laxative use days during past 28 days was associated with current SI, adjusted for vomiting in the same period (p = 0.017). CONCLUSIONS: Current and lifetime laxative misuse were associated with SA history and current SI in patients with ED, at least in part independently of other suicide-related factors. LEVEL OF EVIDENCE: Level III cohort, cross-sectional study.

Impact of Hospitalization in an Endocrinology Department on Vaccination Coverage in People Living with Diabetes: A Real-Life Study.

Background and Objectives: Vaccination coverage is suboptimal in people living with diabetes. The objectives of this study were to determine the impact of hospitalization on vaccination coverage and the variables associated with vaccination during hospital stay. Materials and Methods: This observational study was conducted from May 2019 to December 2019 in the Endocrinology-Nutrition-Diabetes Department of the University Hospital of Montpellier, France. This department encompasses three medical units, two of which have a full-time clinical pharmacist involved in the multidisciplinary management of patients. All adult diabetic patients who completed a questionnaire about vaccines were prospectively included by a clinical pharmacist and followed until department discharge. Coverage at the time of admission for the tetanus, diphtheria, pertussis (Tdap), pneumococcal, influenza, and herpes zoster vaccines was assessed from patient interviews and/or contact with the general practitioner and/or with the community pharmacist. Multivariable logistic regression analysis was performed to identify the factors associated with a vaccination update during the hospital stay. Results: A total of 222 patients were included (mean age: 59.4 years, 68.5% type 2 diabetes). Vaccination coverage increased by 26.7% (47.3% to 59.9%), 188.0% (10.8% to 31.1%) and 8.9% (45.9% to 50.0%), respectively, for the Tdap, pneumococcal and influenza vaccines during hospital stay. Female sex, admission to a diabetes care unit with a full-time pharmacist, favorable feelings about vaccination, unknown immunization coverage for pneumococcal vaccines, and evaluation and recording of vaccine coverage at admission in the patient medical records were associated with at least one vaccination during hospital stay. Conclusions: Our real-life study highlights that hospitalization and multidisciplinary management (i.e., physician-pharmacist) may be key points in the diabetes care pathway to improve vaccination coverage, especially for patients with advanced diabetes and comorbidities.

The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a writing group to develop a consensus statement on the management of type 1 diabetes in adults. The writing group has considered the rapid development of new treatments and technologies and addressed the following topics: diagnosis, aims of management, schedule of care, diabetes self-management education and support, glucose monitoring, insulin therapy, hypoglycaemia, behavioural considerations, psychosocial care, diabetic ketoacidosis, pancreas and islet transplantation, adjunctive therapies, special populations, inpatient management and future perspectives. Although we discuss the schedule for follow-up examinations and testing, we have not included the evaluation and treatment of the chronic microvascular and macrovascular complications of diabetes as these are well-reviewed and discussed elsewhere. The writing group was aware of both national and international guidance on type 1 diabetes and did not seek to replicate this but rather aimed to highlight the major areas that healthcare professionals should consider when managing adults with type 1 diabetes. Though evidence-based where possible, the recommendations in the report represent the consensus opinion of the authors. Graphical abstract.

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.

Hypoglycaemia detection and prediction techniques: A systematic review on the latest developments.

The main objective of diabetes control is to correct hyperglycaemia while avoiding hypoglycaemia, especially in insulin-treated patients. Fear of hypoglycaemia is a hurdle to effective correction of hyperglycaemia because it promotes under-dosing of insulin. Strategies to minimise hypoglycaemia include education and training for improved hypoglycaemia awareness and the development of technologies to allow their early detection and thus minimise their occurrence. Patients with impaired hypoglycaemia awareness would benefit the most from these technologies. The purpose of this systematic review is to review currently available or in-development technologies that support detection of hypoglycaemia or hypoglycaemia risk, and identify gaps in the research. Nanomaterial use in sensors is a promising strategy to increase the accuracy of continuous glucose monitoring devices for low glucose values. Hypoglycaemia is associated with changes on vital signs, so electrocardiogram and encephalogram could also be used to detect hypoglycaemia. Accuracy improvements through multivariable measures can make already marketed galvanic skin response devices a good noninvasive alternative. Breath volatile organic compounds can be detected by dogs and devices and alert patients at hypoglycaemia onset, while near-infrared spectroscopy can also be used as a hypoglycaemia alarms. Finally, one of the main directions of research are deep learning algorithms to analyse continuous glucose monitoring data and provide earlier and more accurate prediction of hypoglycaemia. Current developments for early identification of hypoglycaemia risk combine improvements of available 'needle-type' enzymatic glucose sensors and noninvasive alternatives. Patient usability will be essential to demonstrate to allow their implementation for daily use in diabetes management.

The SAGE study: Global observational analysis of glycaemic control, hypoglycaemia and diabetes management in T1DM.

AIMS: To describe glycaemic control and diabetes management in adults with type 1 diabetes (T1DM), in a real-life global setting. MATERIALS AND METHODS: Study of Adults' GlycEmia (SAGE) was a multinational, multicentre, single visit, noninterventional, cross-sectional study in adult patients with T1DM. Data were collected at a single visit, analysed according to predefined age groups (26-44, 45-64 and ≥65 years) and reported across different regions. The primary endpoint was the proportion of participants achieving HbA1c  less than 7.0 % in each age group. Secondary endpoints included incidence of hypoglycaemia, severe hypoglycaemia and severe hyperglycaemia leading to diabetic ketoacidosis (DKA) and therapeutic management of T1DM. RESULTS: Of 3903 included participants, 3858 (98.8%) were eligible for the study. Overall, 24.3% (95% confidence interval [CI]: 22.9-25.6) of participants achieved the glycaemic target of HbA1c  less than 7.0 %, with more participants achieving this target in the 26-44 years group (27.6% [95% CI: 25.5-29.8]). Target achievement was highest in Eastern and Western Europe, and lowest in the Middle East. The incidence of hypoglycaemia and of severe hyperglycaemia leading to DKA tended to decrease with age, and varied across regions. Age and regional differences were observed in therapeutic management, including types of device/insulin usage, frequency of insulin dose adjustment and technology usage. CONCLUSIONS: Glycaemic control remains poor in adults with T1DM globally. Several areas of treatment may be optimised to improve outcomes, including supporting patient self-management of insulin therapy, increasing use of technologies such as CGM, and greater provision of healthcare support.

Patient-reported outcomes in adults with type 1 diabetes in global real-world clinical practice: The SAGE study.

AIMS: To conduct a secondary analysis of the SAGE study to evaluate the association between glycaemic control and patient-reported outcomes (PROs), in adults with type 1 diabetes (T1DM) across different age groups and regions. MATERIALS AND METHODS: SAGE was a multinational, cross-sectional, observational study in adults with T1DM. Data were collected at a single visit, analysed according to predefined age groups (26-44, 45-64, and ≥65 years), and reported across different regions. PRO questionnaires were applied to assess hypoglycaemia fear (Hypoglycemia Fear Survey-II), diabetes-related distress (Problem Areas In Diabetes questionnaire), insulin treatment satisfaction (Insulin Treatment Satisfaction Questionnaire), and diabetes-specific quality of life (QoL; Audit of Diabetes-Dependent Quality of Life). Multivariable analysis was performed to evaluate the relationship between glycated haemoglobin (HbA1c) target achievement (<7% and individualised targets) with PRO scores. RESULTS: The PRO scores showed relatively low levels of diabetes-related emotional distress and fear of hypoglycaemia, moderate to high treatment satisfaction, and low diabetes-related impact on QoL. Results were generally comparable across age groups with some regional variability. Achievement of the HbA1c <7% target was associated with less worry about hypoglycaemia, lower diabetes-related emotional distress, higher insulin treatment satisfaction, and higher QoL. Achievement of individualised HbA1c targets was associated with lower diabetes-related emotional distress and higher insulin treatment satisfaction. CONCLUSIONS: Better glycaemic control was most closely associated with low emotional distress due to diabetes and high patient-reported insulin treatment satisfaction.

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.

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.

Primary care visits can reduce the risk of potentially avoidable hospitalizations among persons with diabetes in France.

BACKGROUND: Diabetes is a frequent chronic condition, which can lead to costly complications if not managed well in the primary care setting. Potentially avoidable hospitalizations (PAH) are considered as an indirect measure of primary care. However, the association between primary care use and PAH in diabetic patients has not been investigated in France. METHODS: We investigate the association between primary care indicators and PAH at an individual level among persons with diabetes in a population-based cohort study on the French national health insurance database (EGB sample). PAH occurrence in 2013 was modeled as a function of primary care use and access, health status and socio-economic indicators over the exposure period 2011-12 using a cause-specific hazards model with death as a competing event. RESULTS: We included 25 293 diabetics in our cohort, among which 385 (1.5%) experienced at least 1 PAH in 2013. After adjustment on health status indicators, primary care use had a protective effect against PAH. Diabetic patients who had seen a general practitioner (GP) 10-14 times had a reduced hazard of PAH compared to less frequent encounters (HR=0.49, P<0.001). The effect size decreased when the number of encounters increased, suggesting a remaining confounding effect of health status. CONCLUSIONS: For the first time in France, this study shows a protective effect of the number of GP encounters against PAH at an individual level and highlights the importance of a frequent monitoring of diabetic patients in the primary care setting to prevent PAH occurrence.