Development and external validation of a home-based risk predicTion modEl of natUral onseT of menopAuse -TEUTA.

OBJECTIVE: To develop and externally validate a 10-year risk prediction model of natural onset of menopause using ready-to-use predictors. DESIGN: Population-based prospective cohort study. PARTICIPANTS: Community-dwelling, premenopausal women aged 28 years and older enrolled in the Swiss (CoLaus) and Dutch (PREVEND) study. MAIN OUTCOME MEASURE: Incidence of self-reported natural menopause. MODEL DEVELOPMENT: Based on existing literature, 11 predictors were tested in this study. The CoLaus cohort was used to develop the model by applying the backward-elimination approach and Bayesian Model Averaging. Internal validation was performed by bootstrapping. External validation was performed using data from the PREVEND cohort and recalibrating the baseline survival estimate. C-statistic, calibration slopes, and expected/observed probabilities were calculated as measures of model internal and/or external performances. RESULTS: The final analysis included 750 and 1032 premenopausal women from the CoLaus and the PREVEND cohort, respectively. Among them, 445 (59%) from CoLaus and 387 (38%) from PREVEND experienced menopause over a median follow-up of 10.7 and 9 years, respectively. The final model included age, alcohol consumption, smoking status, education level, and systolic blood pressure. Upon external calibration in the PREVEND cohort, the model exhibited good discrimination, with a C-statistic of 0.888 and an expected/observed probability of 0.82. CONCLUSIONS: We present the first internally and externally validated prediction model of natural menopause onset using readily available predictors. Validation of our model to other populations is needed.

Interleaved trinuclear MRS for single-session investigation of carbohydrate and lipid metabolism in human liver at 7T.

The liver plays a central role in metabolic homeostasis, as exemplified by a variety of clinical disorders with hepatic and systemic metabolic disarrays. Of particular interest are the complex interactions between lipid and carbohydrate metabolism in highly prevalent conditions such as obesity, diabetes, and fatty liver disease. Limited accessibility and the need for invasive procedures challenge direct investigations in humans. Hence, noninvasive dynamic evaluations of glycolytic flux and steady-state assessments of lipid levels and composition are crucial for basic understanding and may open new avenues toward novel therapeutic targets. Here, three different MR spectroscopy (MRS) techniques that have been combined in a single interleaved examination in a 7T MR scanner are evaluated. 1 H-MRS and 13 C-MRS probe endogenous metabolites, while deuterium metabolic imaging (DMI) relies on administration of deuterated tracers, currently 2 H-labelled glucose, to map the spatial and temporal evolution of their metabolic fate. All three techniques have been optimized for a robust single-session clinical investigation and applied in a preliminary study of healthy subjects. The use of a triple-channel 1 H/2 H/13 C RF coil enables interleaved examinations with no need for repositioning. Short-echo-time STEAM spectroscopy provides well resolved spectra to quantify lipid content and composition. The relative benefits of using water saturation versus metabolite cycling and types of respiratory synchronization were evaluated. 2 H-MR spectroscopic imaging allowed for registration of time- and space-resolved glucose levels following oral ingestion of 2 H-glucose, while natural abundance 13 C-MRS of glycogen provides a dynamic measure of hepatic glucose storage. For DMI and 13 C-MRS, the measurement precision of the method was estimated to be about 0.2 and about 16 mM, respectively, for 5 min scanning periods. Excellent results were shown for the determination of dynamic uptake of glucose with DMI and lipid profiles with 1 H-MRS, while the determination of changes in glycogen levels by 13 C-MRS is also feasible but somewhat more limited by signal-to-noise ratio.

Postprandial Glucose Excursions with Ultra-Rapid Insulin Analogs in Hybrid Closed-Loop Therapy for Adults with Type 1 Diabetes.

Objective: To evaluate postprandial glucose control when applying (1) faster-acting insulin aspart (Fiasp) compared to insulin aspart and (2) ultra-rapid insulin lispro (Lyumjev) compared to insulin lispro using the CamAPS FX hybrid closed-loop algorithm. Research Design and Methods: We undertook a secondary analysis of postprandial glucose excursions from two double-blind, randomized, crossover hybrid closed-loop studies contrasting Fiasp to standard insulin aspart, and Lyumjev to standard insulin lispro. Endpoints included incremental area under curve (iAUC)-2h, iAUC-4h, 4 h postprandial time in target range, time above range, and time below range. It was approved by independent research ethics committees. Results: Two trials with 8 weeks of data from 51 adults with type 1 diabetes were analyzed and 7137 eligible meals were included. During Lyumjev compared with insulin lispro, iAUC-2h and iAUC-4h were significantly decreased following breakfast (mean difference 92 mmol/L per 2 h (95% confidence interval [CI]: 56 to 127); P < 0.001 and 151 mmol/L per 4 h (95% CI: 74 to 229); P < 0.001, respectively) and the evening meal (P < 0.001 and P = 0.011, respectively). Mean time in target range (3.9-10.0 mmol/L) for 4 h postprandially significantly increased during Lyumjev with a mean difference of 6.7 percentage points (95% CI: 3.3 to 10) and 5.7 percentage points (95% CI: 1.4 to 9.9) for breakfast and evening meal, respectively. In contrast, there were no significant differences in iAUC-2h, iAUC-4h, and the other measures of postprandial glucose control between insulin aspart and Fiasp during breakfast, lunch, and evening meal (P > 0.05). Conclusion: The use of Lyumjev with CamAPS FX closed-loop system improved postprandial glucose excursions compared with insulin lispro, while the use of Fiasp did not provide any advantage compared with insulin aspart. Clinical Trial Registration numbers: NCT04055480, NCT05257460.

Comparator Data Characteristics and Testing Procedures for the Clinical Performance Evaluation of Continuous Glucose Monitoring Systems.

Comparing the performance of different continuous glucose monitoring (CGM) systems is challenging due to the lack of comprehensive guidelines for clinical study design. In particular, the absence of concise requirements for the distribution of comparator (reference) blood glucose (BG) concentrations and their rate of change (RoC) that are used to evaluate CGM performance, impairs comparability. For this article, several experts in the field of CGM performance testing have collaborated to propose characteristics of the distribution of comparator measurements that should be collected during CGM performance testing. Specifically, it is proposed that at least 7.5% of comparator BG concentrations are <70 mg/dL (3.9 mmol/L) and >300 mg/dL (16.7 mmol/L), respectively, and that at least 7.5% of BG-RoC combinations indicate fast BG changes with impending hypo- or hyperglycemia, respectively. These proposed characteristics of the comparator data can facilitate the harmonization of testing conditions across different studies and CGM systems and ensure that the most relevant scenarios representing real-life situations are established during performance testing. In addition, a study protocol and testing procedure for the manipulation of glucose levels are suggested that enable the collection of comparator data with these characteristics. This work is an important step toward establishing a future standard for the performance evaluation of CGM systems.

Selenium Supplementation in Patients with Hashimoto Thyroiditis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background: Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Selenium is an essential trace element required for thyroid hormone synthesis and exerts antioxidant effects. Therefore, it may be of relevance in the management of HT. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of selenium supplementation on thyroid function (thyrotropin [TSH], free and total thyroxine [fT4, T4], free and total triiodothyronine [fT3, T3]), thyroid antibodies (thyroid peroxidase antibodies [TPOAb], thyroglobulin antibodies [TGAb], thyrotropin receptor antibody [TRAb]), ultrasound findings (echogenicity, thyroid volume), immune markers, patient-reported outcomes, and adverse events in HT. The study protocol was registered on PROSPERO (CRD42022308377). We systematically searched MEDLINE, Embase, CINHAL, Web of Science, Google Scholar, and the Cochrane CENTRAL Register of Trials from inception to January 2023 and searched citations of eligible studies. Two independent authors reviewed and coded the identified literature. The primary outcome was TSH in patients without thyroid hormone replacement therapy (THRT); the others were considered secondary outcomes. We synthesized the results as standardized mean differences (SMD) or odds ratio (OR), assessed risk of bias using the Cochrane RoB 2 tool, and rated the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We screened 687 records and included 35 unique studies. Our meta-analysis found that selenium supplementation decreased TSH in patients without THRT (SMD -0.21 [confidence interval, CI -0.43 to -0.02]; 7 cohorts, 869 participants; I2 = 0%). In addition, TPOAb (SMD -0.96 [CI -1.36 to -0.56]; 29 cohorts; 2358 participants; I2 = 90%) and malondialdehyde (MDA; SMD -1.16 [CI -2.29 to -0.02]; 3 cohorts; 248 participants; I2 = 85%) decreased in patients with and without THRT. Adverse effects were comparable between the intervention and control groups (OR 0.89 [CI 0.46 to 1.75]; 16 cohorts; 1339 participants; I2 = 0%). No significant changes were observed in fT4, T4, fT3, T3, TGAb, thyroid volume, interleukin (IL)-2, and IL-10. Overall, certainty of evidence was moderate. Conclusions: In people with HT without THRT, selenium was effective and safe in lowering TSH, TPOAb, and MDA levels. Indications for lowering TPOAb were found independent of THRT.

Utility of iron biomarkers in differentiating menopausal status: Findings from CoLaus and PREVEND.

AIM: To examine the association of iron biomarkers with menopausal status and assess whether these biomarkers can help differentiate menopausal status beyond age. METHODS: In this cross-sectional study we included 1679 women from the CoLaus and 2133 from the PREVEND cohorts, with CoLaus used as primary cohort and PREVEND for replication. Ferritin, transferrin, iron, and transferrin saturation (TSAT) were used to assess iron status. Hepcidin and soluble transferrin receptor were assessed only in PREVEND. Menopausal status was self-reported and defined as menopausal or non-menopausal. Logistic regressions were used to explore the association of these iron biomarkers with menopause status. Sensitivity, specificity, area under the receiver operating characteristic curves (AUC), positive and negative predictive values as well as cut-off points for the iron biomarkers were calculated. The model with the highest AUC was defined as the best. RESULTS: In the CoLaus and PREVEND cohorts, respectively, 513 (30.6 %) and 988 (46.3 %) women were postmenopausal. Ferritin (OR, 2.20; 95 % CI 1.72-2.90), transferrin (OR, 0.03; 95 % CI 0.01-0.10), and TSAT (OR, 1.28; 95 % CI 1.06-1.54) were significantly associated with menopausal status in CoLaus, with the findings replicated in PREVEND. AUC of age alone was 0.971. The best model resulted from combining age, ferritin, and transferrin, with an AUC of 0.976, and sensitivity and specificity of 87.1 % and 96.5 %, respectively. Adding transferrin and ferritin to a model with age improved menopause classification by up to 7.5 %. In PREVEND, a model with age and hepcidin outperformed a model with age, ferritin, and transferrin. CONCLUSION: Iron biomarkers were consistently associated with menopausal status in both cohorts, and modestly improved a model with age alone for differentiating menopause status. Our findings on hepcidin need replication.

Design and Usability Assessment of a User-Centered, Modular Platform for Real-World Data Acquisition in Clinical Trials involving Post-bariatric Surgery Patients.

BACKGROUND: Clinical trials often face challenges in efficient data collection and participant monitoring. To address these issues, we developed the IMPACT platform, comprising a real-time mobile application for data collection and a web-based dashboard for remote monitoring and management. METHODS: This article presents the design, development, and usability assessment of the IMPACT platform customized for patients with post-bariatric surgery hypoglycemia (PBH). We focus on adapting key IMPACT components, including continuous glucose monitoring (CGM), symptom tracking, and meal logging, as crucial elements for user-friendly and efficient PBH monitoring. RESULTS: The adapted IMPACT platform demonstrated effectiveness in data collection and remote participant monitoring. The mobile application allowed patients to easily track their data, while the clinician dashboard provided a comprehensive overview of enrolled patients, featuring filtering options and alert mechanisms for identifying data collection issues. The platform incorporated various visual representations, including time plots and category-based visualizations, which greatly facilitated data interpretation and analysis. The System Usability Scale questionnaire results indicated a high level of usability for the web dashboard, with an average score of 86.3 out of 100. The active involvement of clinicians throughout the development process ensured that the platform allowed for the collection and visualization of clinically meaningful data. CONCLUSIONS: By leveraging IMPACT's existing features and infrastructure, the adapted version streamlined data collection, analysis, and trial customization for PBH research. The platform's high usability underscores its alignment with the requirements for conducting research using continuous real-world data in PBH patients and other populations of interest.

Clinical evaluation of a decision support system for glucose infusion in hypoglycaemic clamp experiments.

AIM: To provide a preliminary evaluation of the accuracy and safety of Gluclas decision support system suggestions in a hypoglycaemic clamp study. METHODS: This analysis was performed using data from 32 participants (four groups with different glucose-insulin regulation: post Roux-en-Y gastric bypass with and without postprandial hypoglycaemia syndrome, postsleeve gastrectomy and non-operated controls) undergoing Gluclas-assisted hypoglycaemic clamps (target: 2.5 mmol/L for 20 minutes at 150 minutes after oral glucose ingestion). Gluclas provided glucose infusion rate suggestions upon manual entry of blood glucose values (every 5 minutes), which were either followed or overruled by investigators after critical review. Accuracy and safety were evaluated by mean absolute error (MAE), mean absolute percentage error (MAPE), average glucose level, coefficient of variation (CV) and minimal glucose level during the 20-minute hypoglycaemic period. RESULTS: Investigators accepted 84% of suggestions, with a mean deviation of 30.33 mg/min. During the hypoglycaemic period, the MAE was 0.16 (0.12-0.24) (median [interquartile range]) mmol/L and the MAPE was 6.12% (4.80%-9.29%). CV was 4.90% (3.58%-7.27%), with 5% considered the threshold for sufficient quality. The minimal glucose level was 2.40 (2.30-2.50) mmol/L. CONCLUSIONS: Gluclas achieved sufficiently high accuracy with minimal safety risks in a population with differences in glucose-insulin dynamics, underscoring its applicability to various patient groups.

A Consensus Statement for Continuous Glucose Monitoring Metrics for Inpatient Clinical Trials.

Diabetes Technology Society organized an expert consensus panel to develop metrics for research in the use of continuous glucose monitors (CGMs) in a hospital setting. The experts met virtually in small groups both before and after an April 13, 2023 virtual meeting of the entire panel. The goal of the panel was to develop consensus definitions in anticipation of greater use of CGMs in hospital settings in the future. Establishment of consensus definitions of inpatient analytical metrics will be easier to compare outcomes between studies. Panelists defined terms related to 10 dimensions of measurements related to the use of CGMs including (1) hospital hypoglycemia, (2) hospital hyperglycemia, (3) hospital time in range, (4) hospital glycemic variability, (5) hospital glycemia risk index, (6) accuracy of CGM devices and reference methods for CGMs in the hospital, (7) meaningful time blocks for hospital glycemic goals, (8) hospital CGM data sufficiency, (9) using CGM data for insulin dosing, and (10) miscellaneous factors. The panelists voted on 51 proposed recommendations. Based on the panel vote, 51 recommendations were classified as either strong (43) or mild (8). Additional research is needed on CGM performance in the hospital. This consensus report is intended to support that type of research intended to improve outcomes for hospitalized people with diabetes.

Relationship Between Symptom Perception and Postprandial Glycemic Profiles in Patients With Postbariatric Hypoglycemia After Roux-en-Y Gastric Bypass Surgery.

OBJECTIVE: Post-bariatric surgery hypoglycemia (PBH) is a metabolic complication of Roux-en-Y gastric bypass (RYGB). Since symptoms are a key component of the Whipple's triad to diagnose nondiabetic hypoglycemia, we evaluated the relationship between self-reported symptoms and postprandial sensor glucose profiles. RESEARCH DESIGN AND METHODS: Thirty patients with PBH after RYGB (age: 50.1 [41.6-60.6] years, 86.7% female, BMI: 26.5 [23.5-31.2] kg/m2; median [interquartile range]) wore a blinded Dexcom G6 sensor while recording autonomic, neuroglycopenic, and gastrointestinal symptoms over 50 days. Symptoms (overall and each type) were categorized into those occurring in postprandial periods (PPPs) without hypoglycemia, or in the preceding dynamic or hypoglycemic phase of PPPs with hypoglycemia (nadir sensor glucose <3.9 mmol/L). We further explored the relationship between symptoms and the maximum negative rate of sensor glucose change and nadir sensor glucose levels. RESULTS: In 5,851 PPPs, 775 symptoms were reported, of which 30.6 (0.0-59.9)% were perceived in PPPs without hypoglycemia, 16.7 (0.0-30.1)% in the preceding dynamic phase and 45.0 (13.7-84.7)% in the hypoglycemic phase of PPPs with hypoglycemia. Per symptom type, 53.6 (23.8-100.0)% of the autonomic, 30.0 (5.6-80.0)% of the neuroglycopenic, and 10.4 (0.0-50.0)% of the gastrointestinal symptoms occurred in the hypoglycemic phase of PPPs with hypoglycemia. Both faster glucose dynamics and lower nadir sensor glucose levels were related with symptom perception. CONCLUSIONS: The relationship between symptom perception and PBH is complex, challenging clinical judgement and decision-making in this population.

Nutritional strategies for correcting low glucose values in patients with postbariatric hypoglycaemia: A randomized controlled three-arm crossover trial.

AIM: To evaluate the efficacy of nutritional hypoglycaemia correction strategies in postbariatric hypoglycaemia (PBH) after Roux-en-Y gastric bypass (RYGB). MATERIALS AND METHODS: In a randomized, controlled, three-arm crossover trial, eight post-RYGB adults (mean [SD] 7.0 [1.4] years since surgery) with PBH ingested a solid mixed meal (584 kcal, 85 g carbohydrates, 21 g fat, 12 g protein) to induce hypoglycaemia on three separate days. Upon reaching plasma glucose of less than 3.0 mmol/L, hypoglycaemia was corrected with 15 g of glucose (G15), 5 g of glucose (G5) or a protein bar (P10, 10 g of protein) in random order. The primary outcome was percentage of time spent in the target plasma glucose range (3.9-5.5 mmol/L) during 40 minutes after correction. RESULTS: Postcorrection time spent in the target glucose range did not differ significantly between the interventions (P = .161). However, postcorrection time with glucose less than 3.9 mmol/L was lower after G15 than P10 (P = .007), whereas time spent with glucose more than 5.5 mmol/L, peak glucose and insulin 15 minutes postcorrection were higher after G15 than G5 and P10 (P < .001). Glucagon 15 minutes postcorrection was higher after P10 than after G15 and G5 (P = .002 and P = .003, respectively). G15 resulted in rebound hypoglycaemia (< 3.0 mmol/L) in three of eight cases (38%), while no rebound hypoglycaemia occurred with G5 and P10. CONCLUSIONS: Correcting hypoglycaemia with 15 g of glucose should be reconsidered in post-RYGB PBH. A lower dose appears to sufficiently increase glucose levels outside the critical range in most cases, and complementary nutrients (e.g. proteins) may provide glycaemia-stabilizing benefits. REGISTRATION NUMBER OF CLINICAL TRIAL: NTC05250271 (ClinicalTrials.gov).

Time Spent in Hypoglycemia According to Age and Time of Day: Observations During Closed-Loop Insulin Delivery.

Objective: We aimed to assess whether percentage of time spent in hypoglycemia during closed-loop insulin delivery differs by age group and time of day. Methods: We retrospectively analyzed data from hybrid closed-loop studies involving young children (2-7 years), children and adolescents (8-18 years), adults (19-59 years), and older adults (≥60 years) with type 1 diabetes. Main outcome was time spent in hypoglycemia <3.9 mmol/L (<70 mg/dL). Eight weeks of data for 88 participants were analyzed. Results: Median time spent in hypoglycemia over the 24-h period was highest in children and adolescents (4.4% [interquartile range 2.4-5.0]) and very young children (4.0% [3.4-5.2]), followed by adults (2.7% [1.7-4.0]), and older adults (1.8% [1.2-2.2]); P < 0.001 for difference between age groups. Time spent in hypoglycemia during nighttime (midnight-05:59) was lower than during daytime (06:00-23:59) across all age groups. Conclusion: Time in hypoglycemia was highest in the pediatric age group during closed-loop insulin delivery. Hypoglycemia burden was lowest overnight across all age groups.

Biomarkers for the Diagnosis of Heart Failure in People with Diabetes: A Consensus Report from Diabetes Technology Society.

Diabetes Technology Society assembled a panel of clinician experts in diabetology, cardiology, clinical chemistry, nephrology, and primary care to review the current evidence on biomarker screening of people with diabetes (PWD) for heart failure (HF), who are, by definition, at risk for HF (Stage A HF). This consensus report reviews features of HF in PWD from the perspectives of 1) epidemiology, 2) classification of stages, 3) pathophysiology, 4) biomarkers for diagnosing, 5) biomarker assays, 6) diagnostic accuracy of biomarkers, 7) benefits of biomarker screening, 8) consensus recommendations for biomarker screening, 9) stratification of Stage B HF, 10) echocardiographic screening, 11) management of Stage A and Stage B HF, and 12) future directions. The Diabetes Technology Society panel recommends 1) biomarker screening with one of two circulating natriuretic peptides (B-type natriuretic peptide or N-terminal prohormone of B-type natriuretic peptide), 2) beginning screening five years following diagnosis of type 1 diabetes (T1D) and at the diagnosis of type 2 diabetes (T2D), 3) beginning routine screening no earlier than at age 30 years for T1D (irrespective of age of diagnosis) and at any age for T2D, 4) screening annually, and 5) testing any time of day. The panel also recommends that an abnormal biomarker test defines asymptomatic preclinical HF (Stage B HF). This diagnosis requires follow-up using transthoracic echocardiography for classification into one of four subcategories of Stage B HF, corresponding to risk of progression to symptomatic clinical HF (Stage C HF). These recommendations will allow identification and management of Stage A and Stage B HF in PWD to prevent progression to Stage C HF or advanced HF (Stage D HF).

Clinical evidence for high-risk medical devices used to manage diabetes: protocol for a systematic review and meta-analysis.

INTRODUCTION: Medical devices, including high-risk medical devices, have greatly contributed to recent improvements in the management of diabetes. However, the clinical evidence that is submitted for regulatory approval is not transparent, and thus a comprehensive summary of the evidence for high-risk devices approved for managing diabetes in Europe is lacking. In the framework of the Coordinating Research and Evidence for Medical Devices group, we will, therefore, perform a systematic review and meta-analysis, which will evaluate the efficacy, safety and usability of high-risk medical devices for the management of diabetes. METHOD AND ANALYSIS: This study has been reported according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will search Embase (Elsevier), Medline All (Ovid), Cochrane Library (Wiley), Science Citation Index Expanded and Emerging Sources Citation Index (Web of Science) to identify interventional and observational studies that evaluate the efficacy and/or safety and/or usability of high-risk medical devices for the management of diabetes. No language or publication dates' limits will be applied. Animal studies will be excluded. In accordance with the Medical Device Regulation in European Union, high-risk medical devices are those in classes IIb and III. The following medical devices for diabetes management are considered as having a high risk: implantable continuous glucose monitoring systems, implantable pumps and automated insulin delivery devices. Selection of studies, data extraction and quality of evidence assessment will be performed independently by two researchers. Sensitivity analysis will be performed to identify and explain potential heterogeneity. ETHICS AND DISSEMINATION: No ethical approval is needed for this systematic review, as it is based in already published data. Our findings will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022366871.

Time requirements for perioperative glucose management using fully closed-loop versus standard insulin therapy: A proof-of-concept time-motion study.

AIMS: To compare the time required for perioperative glucose management using fully automated closed-loop versus standard insulin therapy. METHODS: We performed a time-motion study to quantify the time requirements for perioperative glucose management with fully closed-loop (FCL) and standard insulin therapy applied to theoretical scenarios. Following an analysis of workflows in different periods of perioperative care in elective surgery patients receiving FCL or standard insulin therapy upon hospital admission (pre- and intra-operatively, at the intermediate care unit and general wards), the time of process-specific tasks was measured by shadowing hospital staff. Each task was measured 20 times and its average duration in combination with its frequency according to guidelines was used to calculate the cumulative staff time required for blood glucose management. Cumulative time was calculated for theoretical scenarios consisting of elective minor and major abdominal surgeries (pancreatic surgery and sleeve gastrectomy, respectively) to account for the different care settings and lengths of stay. RESULTS: The FCL insulin therapy reduced the time required for perioperative glucose management compared to standard insulin therapy, across all assessed care periods and for both perioperative pathways (range 2.1-4.5). For a major abdominal surgery, total time required was 248.5 min using FCL versus 753.9 min using standard insulin therapy. For a minor abdominal surgery, total time required was 68.6 min and 133.2 min for FCL and standard insulin therapy, respectively. CONCLUSIONS: The use of fully automated closed-loop insulin delivery for inpatient glucose management has the potential to alleviate the workload of diabetes management in an environment with adequately trained staff.

Randomized, Double-Blind, Placebo-Controlled Crossover Trial of Once Daily Empagliflozin 25 mg for the Treatment of Postprandial Hypoglycemia After Roux-en-Y Gastric Bypass.

Aims: To investigate the effect of empagliflozin on glucose dynamics in individuals suffering from postbariatric hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB). Methods: Twenty-two adults with PBH after RYGB were randomized to empagliflozin 25 mg or placebo once daily over 20 days in a randomized, double-blind, placebo-controlled, crossover trial. The primary efficacy outcome was the amplitude of plasma glucose excursion (peak to nadir) during a mixed-meal tolerance test (MMTT). Outcomes of the outpatient period were assessed using continuous glucose monitoring (CGM) and an event-tracking app. Results: The amplitude of glucose excursion during the MMTT was 8.1 ± 2.4 mmol/L with empagliflozin versus 8.1 ± 2.6 mmol/L with placebo (mean ± standard deviation, P = 0.807). CGM-based mean amplitude of glucose excursion during the 20-day period was lower with empagliflozin than placebo (4.8 ± 1.3 vs. 5.2 ± 1.6. P = 0.028). Empagliflozin reduced the time spent with CGM values >10.0 mmol/L (3.8 ± 3.5% vs. 4.7 ± 3.8%, P = 0.009), but not the time spent with CGM values <3.0 mmol/L (1.7 ± 1.6% vs. 1.5 ± 1.5%, P = 0.457). No significant difference was observed in the quantity and quality of recorded symptoms. Eleven adverse events occurred with empagliflozin (three drug-related) and six with placebo. Conclusions: Empagliflozin 25 mg reduces glucose excursions but not hypoglycemia in individuals with PBH. Clinical Trial Registration: Clinicaltrials.gov: NCT05057819.

Fostering physical activity-related health competence after bariatric surgery with a multimodal exercise programme: A randomised controlled trial.

Regular physical activity (PA) supports the long-term success of bariatric surgery. However, integrating health-enhancing physical activity in daily life requires specific competences. In this study, we evaluated a multimodal exercise programme to build these competences.Forty adults who underwent bariatric surgery were randomised to a multimodal exercise programme or control group. Primary outcomes were the facets of PA-related health competences, namely the control competence for physical training, PA-specific affect regulation, motivational competence and PA-specific self-control. Secondary outcomes were PA behaviour and subjective vitality. Outcomes were assessed before, directly after the intervention and at 3 months follow-up.Significant treatment effects were found for control competence for physical training and PA-specific self-control but not for PA-specific affect regulation and motivational competence. Significant treatment effects were further observed for self-reported exercise and subjective vitality, all in favour of the intervention group. In contrast, no treatment effect was found for device-based PA. Overall, this study provides a foundation for future research to optimise long-term post bariatric surgery outcomes.

Characteristics of inflammatory response and repair after experimental blast lung injury in rats.

BACKGROUND AND OBJECTIVES: Blast-induced lung injury is associated with inflammatory, which are characterised by disruption of the alveolar-capillary barrier, haemorrhage, pulmonary infiltrateration causing oedema formation, pro-inflammatory cytokine and chemokine release, and anti-inflammatory counter-regulation. The objective of the current study was to define sequence of such alterations in with establishing blast-induced lung injury in rats using an advanced blast generator. METHODS: Rats underwent a standardized blast wave trauma and were euthanised at defined time points. Non-traumatised animals served as sham controls. Obtained samples from bronchoalveolar lavage fluid (BALF) at each time-point were assessed for histology, leukocyte infiltration and cytokine/chemokine profile. RESULTS: After blast lung injury, significant haemorrhage and neutrophil infiltration were observed. Similarly, protein accumulation, lactate dehydrogenase activity (LDH), alveolar eicosanoid release, matrix metalloproteinase (MMP)-2 and -9, pro-Inflammatory cytokines, including tumour necrosis factor (TNF) and interleukin (IL) -6 raised up. While declining in the level of anti-inflammatory cytokine IL-10 occurred. Ultimately, pulmonary oedema developed that increased to its maximum level within the first 1.5 h, then recovered within 24 h. CONCLUSION: Using a stablished model, can facilitate the study of inflammatory response to blast lung injury. Following the blast injury, alteration in cytokine/chemokine profile and activity of cells in the alveolar space occurs, which eventuates in alveolar epithelial barrier dysfunction and oedema formation. Most of these parameters exhibit time-dependent return to their basal status that is an indication to resilience of lungs to blast-induced lung injury.