Perioperative Fully Closed-loop versus Usual Care Glucose Management in Adults Undergoing Major Abdominal Surgery - A Two-centre Randomised Controlled Trial.

OBJECTIVE: To assess the efficacy and safety of fully closed-loop (FCL) compared with usual care (UC) glucose control in patients experiencing major abdominal surgery-related stress hyperglycaemia. SUMMARY BACKGROUND DATA: Major abdominal surgery-related stress and periprocedural interventions predispose to perioperative hyperglycaemia, both in diabetes and non-diabetes patients. Insulin corrects hyperglycaemia effectively, but its safe use remains challenging. METHODS: In this two-centre randomised controlled trial, we contrasted subcutaneous FCL with UC glucose management in patients undergoing major abdominal surgery anticipated to experience prolonged hyperglycaemia. FCL (CamAPS HX, Dexcom G6, mylife YpsoPump 1.5x) or UC treatment was used from hospital admission to discharge (max 20 d). Glucose control was assessed using continuous glucose monitoring (masked in the UC group). The primary outcome was the proportion of time with sensor glucose values in target range 5.6-10.0 mmol/L. RESULTS: Thirty-seven surgical patients (54% pancreas, 22% liver, 19% upper gastrointestinal, 5% lower gastrointestinal), of whom 18 received FCL and 19 UC glucose management, were included in the analysis. Mean±SD percentage time with sensor glucose in target range was 80.1±10.0% in the FCL and 53.7±19.7% in the UC group (P<0.001). Mean±SD glucose was 7.5±0.5 mmol/L in the FCL and 9.1±2.4 mmol/L in the UC group (P=0.015). Time in hypoglycaemia (<3.0 mmol/L) was low in either group. No study-related serious adverse events occurred. CONCLUSIONS: The FCL approach resulted in significantly better glycaemic control compared to UC management, without increasing the risk of hypoglycaemia. Automated glucose-responsive insulin delivery is a safe and effective strategy to minimise hyperglycaemia in complex surgical populations.

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. 1H-MRS and 13C-MRS probe endogenous metabolites, while deuterium metabolic imaging (DMI) relies on administration of deuterated tracers, currently 2H-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 1H/2H/13C 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. 2H-MR spectroscopic imaging allowed for registration of time- and space-resolved glucose levels following oral ingestion of 2H-glucose, while natural abundance 13C-MRS of glycogen provides a dynamic measure of hepatic glucose storage. For DMI and 13C-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 1H-MRS, while the determination of changes in glycogen levels by 13C-MRS is also feasible but somewhat more limited by signal-to-noise ratio.

Clinical evidence for high-risk CE-marked medical devices for glucose management: A systematic review and meta-analysis.

AIMS: To conduct a systematic review and meta-analysis, within the Coordinating Research and Evidence for Medical Devices (CORE-MD) project, evaluating CE-marked high-risk devices for glucose management. MATERIALS AND METHODS: We identified interventional and observational studies evaluating the efficacy and safety of eight automated insulin delivery (AID) systems, two implantable insulin pumps, and three implantable continuous glucose monitoring (CGM) devices. We meta-analysed randomized controlled trials (RCTs) comparing AID systems with other treatments. RESULTS: A total of 182 studies published between 2009 and 2024 were included, comprising 166 studies on AID systems, six on insulin pumps, and 10 on CGM devices; 26% reported industry funding; 18% were pre-market; 37% had a comparator group. Of the studies identified, 29% were RCTs, 24% were non-randomized trials, and 47% were observational studies. The median (interquartile range) sample size was 48 (28-102), age 34.8 (14-44.2) years, and study duration 17.5 (12-26) weeks. AID systems lowered glycated haemoglobin by 0.5 percentage points (absolute mean difference [MD] = -0.5; 21 RCTs; I2 = 86%) and increased time in target range for sensor glucose level by 13.4 percentage points (MD = 13.4; 14 RCTs; I2 = 90%). At least one safety outcome was assessed in 71% of studies. CONCLUSIONS: High-risk devices for glucose monitoring or insulin dosing, in particular AID systems, improve glucose control safely, but evidence on diabetes-related end-organ damage is lacking due to short study durations. Methodological heterogeneity highlights the need for developing standards for future pre- and post-market investigations of diabetes-specific high-risk medical devices.

In vivo mapping of postprandial hepatic glucose metabolism using dynamic magnetic resonance spectroscopy combined with stable isotope flux analysis in Roux-en-Y gastric bypass adults and non-operated controls: A case-control study.

AIMS: Roux-en-Y gastric bypass (RYGB) surgery alters postprandial glucose profiles, causing post-bariatric hypoglycaemia (PBH) in some individuals. Due to the liver's central role in glucose homeostasis, hepatic glucose handling might differ in RYGB-operated patients with PBH compared to non-operated healthy controls (HC). MATERIALS AND METHODS: We enrolled RYGB-operated adults with PBH and HCs (n = 10 each). Participants ingested 60 g of [6,6'-2H2]-glucose (d-glucose) after an overnight fast. Deuterium metabolic imaging (DMI) with interleaved 13C magnetic resonance spectroscopy was performed before and until 150 min post-d-glucose intake, with frequent blood sampling to quantify glucose enrichment and gluco-regulatory hormones until 180 min. Glucose fluxes were assessed by mathematical modelling. Outcome trajectories were described using generalized additive models. RESULTS: In RYGB subjects, the hepatic d-glucose signal increased early, followed by a decrease, whereas HCs exhibited a gradual increase and consecutive stabilization. Postprandial hepatic glycogen accumulation and the suppression of endogenous glucose production were lower in RYGB patients than in HCs, despite higher insulin exposure, indicating lower hepatic insulin sensitivity. The systemic rate of ingested d-glucose was faster in RYGB, leading to a higher, earlier plasma glucose peak and increased insulin secretion. Postprandial glucose disposal increased in RYGB patients, without between-group differences in peripheral insulin sensitivity. CONCLUSIONS: Exploiting DMI with stable isotope flux analysis, we observed distinct postprandial hepatic glucose trajectories and parameters of glucose-insulin homeostasis in RYGB patients with PBH versus HCs. Despite altered postprandial glucose kinetics and higher insulin exposure, there was no evidence of impaired hepatic glucose uptake or output predisposing to PBH in RYGB patients.

In Vitro Investigation of Insulin Dynamics During 4 Hours of Simulated Cardiopulmonary Bypass.

BACKGROUND: Hyperglycemia is common in patients undergoing cardiovascular surgery with cardiopulmonary bypass. We hypothesize that intraoperative hyperglycemia may be, at least partially, attributable to insulin loss due to adhesion on artificial surfaces and/or degradation by hemolysis. Thus, our primary aim was to investigate the loss of insulin in 2 different isolated extracorporeal circulation circuits (ECCs), that is, a conventional ECC (cECC) with a roller pump, and a mini-ECC (MiECC) system with a centrifugal pump. The secondary aim was to assess and compare the relationship between changes in insulin concentration and the degree of hemolysis in our 2 ECC models. METHODS: Six cECC and 6 MiECC systems were primed with red packed blood cells and thawed fresh-frozen plasma (1:1). Four additional experiments were performed in cECC using only thawed fresh-frozen plasma. Human insulin (Actrapid) was added, targeting a plasma insulin concentration of 400 mU/L. Insulin concentration and hemolysis index were measured at baseline and hourly thereafter. The end points were the change in insulin level after 4 hours compared to baseline and hemolysis index after 4 hours. The insulin concentration and hemolysis index were analyzed by means of a saturated linear mixed-effect regression model with a random offset for each experiment to account for the repeated measure design of the study, resulting in mean estimates and 95% confidence intervals (CIs) of the primary end points as well as of pairwise contrasts with respect to ECC type. RESULTS: Insulin concentration decreased by 63% (95% CI, 48%-77%) in the MiECC and 92% (95% CI, 77%-106%) in the cECC system that contained red blood cells. Insulin loss was significantly higher in the cECC system compared to the MiECC (P = .022). In the cECC with only plasma, insulin did not significantly decrease (-4%; 95% CI, -21% to 14%). Hemolysis index in MiECC increased from 68 (95% CI, 46-91) to 76 (95% CI, 54-98) after 4 hours, in cECC from 81 (95% CI, 59-103) to 121 (95% CI, 99-143). Hemolysis index and percent change of insulin showed an excellent relationship (r = -0.99, P < .01). CONCLUSIONS: Our data showed that insulin levels substantially decreased during 4 hours of simulated cardiopulmonary bypass only in the ECC that contained hemoglobin. The decrease was more pronounced in the cECC, which also exhibited a greater degree of hemolysis. Our results suggest that insulin degradation by hemolysis products may be a stronger contributor to insulin loss than adhesion of insulin molecules to circuit surfaces.

[Formula diets for weight loss - chances and challenges]. / Formula-Diäten für den Gewichtsverlust ­ Chancen und Herausforderungen.

INTRODUCTION: Formula diets, through the use of industrially manufactured meal replacement products, lead to effective and rapid weight reduction and improvement in obesity-associated comorbidities. The specific composition of these meal replacement products simplifies the adherence to calorie goals and ensures the supply of essential nutrients during significant energy restriction. Despite numerous potential applications, evidence from randomized controlled studies, and simplicity in practical implementation, challenges persist. Monotony and social restrictions complicate adherence and acceptance. The use of formula diets for sustainable weight loss requires integration into a multimodal treatment approach with the goal of long-term changes in eating and activity behaviour. This includes accompanying nutritional counselling, promotion of physical activity, evaluation of adjuvant pharmacological or interventional therapies, as well as psychological support. The development of new incretin-based anti-obesity medications has opened another application field for formula products. There is optimization potential in expanding the product range and combining it with digital applications to enhance acceptance and reach a larger patient group.

Counter-regulatory responses to postprandial hypoglycaemia in patients with post-bariatric hypoglycaemia vs surgical and non-surgical control individuals.

AIMS/HYPOTHESIS: Post-bariatric hypoglycaemia is an increasingly recognised complication of bariatric surgery, manifesting particularly after Roux-en-Y gastric bypass. While hyperinsulinaemia is an established pathophysiological feature, the role of counter-regulation remains unclear. We aimed to assess counter-regulatory hormones and glucose fluxes during insulin-induced postprandial hypoglycaemia in patients with post-bariatric hypoglycaemia after Roux-en-Y gastric bypass vs surgical and non-surgical control individuals. METHODS: In this case-control study, 32 adults belonging to four groups with comparable age, sex and BMI (patients with post-bariatric hypoglycaemia, Roux-en-Y gastric bypass, sleeve gastrectomy and non-surgical control individuals) underwent a postprandial hypoglycaemic clamp in our clinical research unit to reach the glycaemic target of 2.5 mmol/l 150-170 min after ingesting 15 g of glucose. Glucose fluxes were assessed during the postprandial and hypoglycaemic period using a dual-tracer approach. The primary outcome was the incremental AUC of glucagon during hypoglycaemia. Catecholamines, cortisol, growth hormone, pancreatic polypeptide and endogenous glucose production were also analysed during hypoglycaemia. RESULTS: The rate of glucose appearance after oral administration, as well as the rates of total glucose appearance and glucose disappearance, were higher in both Roux-en-Y gastric bypass groups vs the non-surgical control group in the early postprandial period (all p<0.05). During hypoglycaemia, glucagon exposure was significantly lower in all surgical groups vs the non-surgical control group (all p<0.01). Pancreatic polypeptide levels were significantly lower in patients with post-bariatric hypoglycaemia vs the non-surgical control group (median [IQR]: 24.7 [10.9, 38.7] pmol/l vs 238.7 [186.3, 288.9] pmol/l) (p=0.005). Other hormonal responses to hypoglycaemia and endogenous glucose production did not significantly differ between the groups. CONCLUSIONS/INTERPRETATION: The glucagon response to insulin-induced postprandial hypoglycaemia is lower in post-bariatric surgery individuals compared with non-surgical control individuals, irrespective of the surgical modality. No significant differences were found between patients with post-bariatric hypoglycaemia and surgical control individuals, suggesting that impaired counter-regulation is not a root cause of post-bariatric hypoglycaemia. TRIAL REGISTRATION: ClinicalTrials.gov NCT04334161.

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.

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.

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).

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.

Association Between Ultra-Processed Food Intake and All-Cause Mortality: A Systematic Review and Meta-Analysis.

Consumption of ultra-processed foods (UPF) has increased worldwide during the last decades because they are hyperpalatable, cheap, and ready-to-consume products. However, uncertainty exists about their impact on health. We conducted a systematic review and meta-analysis evaluating the association of UPF consumption with all-cause mortality risk. Five bibliographic databases were searched for relevant studies. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). Of 6,951 unique citations, 40 unique prospective cohort studies comprising 5,750,133 individuals were included; publication dates ranged from 1984 to 2021. Compared with low consumption, highest consumption of UPF (RR = 1.29, 95% CI: 1.17, 1.42), sugar-sweetened beverages (RR = 1.11, 95% CI, 1.04, 1.18), artificially sweetened beverages (RR = 1.14, 95% CI, 1.05, 1.22), and processed meat/red meat (RR = 1.15, 95% CI, 1.10, 1.21) were significantly associated with increased risk of mortality. However, breakfast cereals were associated with a lower mortality risk (RR = 0.85, 95% CI, 0.79, 0.92). This meta-analysis suggests that high consumption of UPF, sugar-sweetened beverages, artificially sweetened beverages, processed meat, and processed red meat might increase all-cause mortality, while breakfast cereals might decrease it. Future studies are needed to address lack of standardized methods in UPF categorization.

Multiplexed Assay to Quantify the PP-Fold Family of Peptides in Human Plasma Using Microflow Liquid Chromatography-Tandem Mass Spectrometry.

BACKGROUND: Peptide Tyr-Tyr (PYY1-36), pancreatic polypeptide (PP1-36) and neuropeptide Y (NPY1-36) constitute the PP-fold family of peptides that is involved in metabolic regulation. Very low plasma concentrations and cleavage into active 3-36 fragments challenge bioanalytical assays used for the quantification of these peptides. METHODS: We developed a multiplexed isotopic dilution assay to quantify PYY1-36, PP1-36, and NPY1-36 and their dipeptidyl peptidase-4 (DPP4)-derived metabolites PYY3-36, PP3-36 and NPY3-36. All peptides were immunocaptured from plasma using a monoclonal antibody and quantified by micro-ultra-HPLC-MS/MS. Blood samples from healthy volunteers were collected fasting and 30 min after nutrient stimulation. Method comparison was performed with commercial immunoassays. RESULTS: Linearity was shown in the measured intervals (r2 > 0.99). The lower limit of quantification (LLOQ) with a CV at 20% was 1.5 pM for PYY1-36 and PYY3-36, 3.0 pM for PP1-36 and PP3-36, 0.8 pM for NPY1-36 and 0.5 pM for NPY3-36. In all cases, intra- and inter-assay bias and imprecision were <21%. Pre-analytical stability required addition of a protease inhibitor cocktail. Physiological concentrations of PYY3-36, NPY3-36, PP1-36 and PP3-36 were above the LLOQ in 43% to 100% of the samples. PYY1-36 and NPY1-36 were above the LLOQ in 9% and 0% of the samples, respectively. Immunoassays showed higher concentrations of measurands and poor agreement when compared with micro-UHPLC-MS/MS. CONCLUSIONS: The assay allowed for specific multiplexed analysis of the PP-fold family of peptides and their DPP4-cleaved fragments in a single sample, thereby offering new perspectives to study the role and therapeutic potential of these essential peptide hormones in health and metabolic disease.

Importance of Carbohydrate Quality: What Does It Mean and How to Measure It?

Dietary carbohydrates are our main source of energy. Traditionally, they are classified based on the polymer length between simple and complex carbohydrates, which does not necessarily reflect their impact on health. Simple sugars, such as fructose, glucose, and lactose, despite having a similar energy efficiency and caloric content, have very distinct metabolic effects, leading to increased risk for various chronic diseases when consumed in excess. In addition, beyond the absolute amount of carbohydrate consumed, recent data point out that the food form or processing level can modulate both the energy efficiency and the cardiometabolic risk associated with specific carbohydrates. To account for both of these aspects-the quality of carbohydrates as well as its food form-several metrics can be proposed to help identifying carbohydrate-rich food sources and distinguish between those that would favor the development of chronic diseases and those that may contribute to prevent these. This review summarizes the findings presented during the American Society of Nutrition Satellite symposium on carbohydrate quality, in which these different aspects were presented.

Association of diabetes mellitus and admission glucose levels with outcome after endovascular therapy in acute ischaemic stroke in anterior circulation.

BACKGROUND AND PURPOSE: We aimed to assess the association of diabetes mellitus (DM) and admission hyperglycaemia (AH), respectively, and outcome in patients with acute ischaemic stroke with large vessel occlusion in the anterior circulation treated with endovascular therapy (EVT) in daily clinical practice. METHODS: Consecutive EVT patients admitted to our stroke centre between February 2015 and April 2020 were included in this observational cohort study. Patients with versus without DM and with versus without AH (glucose ≥ 7.8 mmol/L) were compared. RESULTS: We included 1020 patients (48.9% women, median age = 73.1 years); 282 (27.6%) had DM, and 226 (22.2%) had AH. Patients with versus without DM less often showed successful reperfusion (odds ratio [OR]adjusted  = 0.61, p = 0.023) and worse 3-month functional outcome (modified Rankin Scale [mRS] = 0-2: 31.3% vs. 48%, ORadjusted  = 0.59, p = 0.004; death: 38.9% vs. 24.1%, ORadjusted  = 1.75, p = 0.002; mRS shift: padjusted  < 0.0001; if moderate/good collaterals and mismatch, mRS = 0-2: ORadjusted  = 0.52, p = 0.005; death: ORadjusted  = 1.95, p = 0.005). If analysis was additionally adjusted for AH, only mRS shift was still significantly worse in patients with DM (padjusted  = 0.012). Patients with versus without AH showed similar successful reperfusion rates and worse 3-month functional outcome (mRS = 0-2: 28.3% vs. 50.4%, ORadjusted  = 0.52, p < 0.0001; death: 40.4% vs. 22.4%, ORadjusted  = 1.80, p = 0.001; mRS shift: padjusted  < 0.0001; if moderate/good collaterals and mismatch, mRS = 0-2: ORadjusted  = 0.38, p < 0.0001; death: ORadjusted  = 2.39, p < 0.0001). If analysis was additionally adjusted for DM, 3-month functional outcome remained significantly worse in patients with AH (mRS = 0-2: ORadjusted  = 0.58, p = 0.004; death: ORadjusted  = 1.57, p = 0.014; mRS shift: padjusted  = 0.004). DM independently predicted recurrent/progressive in-hospital ischaemic stroke (OR = 1.71, p = 0.043) together with admission National Institutes of Health Stroke Scale score (OR = 0.95, p = 0.005), and AH independently predicted in-hospital symptomatic intracranial haemorrhage (OR = 2.21, p = 0.001). The association of admission continuous glucose levels and most outcome variables was (inversely) J-shaped. CONCLUSIONS: Hyperglycaemia more than DM was associated with worse 3-month outcome in the patients studied, more likely so in the case of moderate/good collaterals and mismatch in admission imaging.

Insufficient weight loss after banded vs. non-banded primary gastric bypass surgery: insights from an observational 5 year follow-up study.

BACKGROUND: While Roux-en-Y gastric bypass (RYGB) is effective in achieving weight loss and improving obesity-related co-morbidities, insufficient weight loss in the long-term can occur. The goal was to assess whether banded vs. non-banded RYGB reduces the risk of insufficient weight loss at 5-year follow-up. METHODS: This is a retrospective single-center cohort study from Switzerland. We assessed the 5-year metabolic trajectories in terms of body weight, body mass index, glucose control, lipid profile and blood pressure of two surgical cohorts undergoing identical RYGB procedures with or without banding using a uniform 6.5 cm silastic Fobi band. Insufficient weight loss was defined as < 50% excess weight loss (EWL) at 5 years. RESULTS: A total of 55 patients receiving banded (Fobi) and 55 patients receiving non-banded (non-Fobi) RYGB were included in the analysis. 5-year follow-up was 91% for both groups. Percentage of EWL at 5 years was 78.11 ± 26.1% and 73.5 ± 27%.3 for the Fobi vs. non-Fobi group (p = 0.368), respectively. Insufficient weight loss (defined as < 50%EWL) at 5 years or last follow-up was significantly higher in the non-Fobi group compared to the Fobi group (19/55 vs. 9/55, respectively, OR = 2.639 (95% CI 1.066, 6.531), p = 0.036). Surrogate markers for cardiometabolic outcomes consistently improved over time, without differences between the groups. During the follow-up period, Fobi-removal was necessary in nine patients (16.3%). CONCLUSION: Banded-RYGB lowered the odds of insufficient weight loss at 5 years follow-up by approximately 62%. Further research is needed to explore the effect of restriction on eating behaviour and neuroendocrine responses after RYGB.

Closed-Loop Insulin Delivery for Glycemic Control in Noncritical Care.

BACKGROUND: In patients with diabetes, hospitalization can complicate the achievement of recommended glycemic targets. There is increasing evidence that a closed-loop delivery system (artificial pancreas) can improve glucose control in patients with type 1 diabetes. We wanted to investigate whether a closed-loop system could also improve glycemic control in patients with type 2 diabetes who were receiving noncritical care. METHODS: In this randomized, open-label trial conducted on general wards in two tertiary hospitals located in the United Kingdom and Switzerland, we assigned 136 adults with type 2 diabetes who required subcutaneous insulin therapy to receive either closed-loop insulin delivery (70 patients) or conventional subcutaneous insulin therapy, according to local clinical practice (66 patients). The primary end point was the percentage of time that the sensor glucose measurement was within the target range of 100 to 180 mg per deciliter (5.6 to 10.0 mmol per liter) for up to 15 days or until hospital discharge. RESULTS: The mean (±SD) percentage of time that the sensor glucose measurement was in the target range was 65.8±16.8% in the closed-loop group and 41.5±16.9% in the control group, a difference of 24.3±2.9 percentage points (95% confidence interval [CI], 18.6 to 30.0; P<0.001); values above the target range were found in 23.6±16.6% and 49.5±22.8% of the patients, respectively, a difference of 25.9±3.4 percentage points (95% CI, 19.2 to 32.7; P<0.001). The mean glucose level was 154 mg per deciliter (8.5 mmol per liter) in the closed-loop group and 188 mg per deciliter (10.4 mmol per liter) in the control group (P<0.001). There was no significant between-group difference in the duration of hypoglycemia (as defined by a sensor glucose measurement of <54 mg per deciliter; P=0.80) or in the amount of insulin that was delivered (median dose, 44.4 U and 40.2 U, respectively; P=0.50). No episode of severe hypoglycemia or clinically significant hyperglycemia with ketonemia occurred in either trial group. CONCLUSIONS: Among inpatients with type 2 diabetes receiving noncritical care, the use of an automated, closed-loop insulin-delivery system resulted in significantly better glycemic control than conventional subcutaneous insulin therapy, without a higher risk of hypoglycemia. (Funded by Diabetes UK and others; ClinicalTrials.gov number, NCT01774565 .).

Menopausal Transition Is Not Associated with Dietary Change in Swiss Women.

BACKGROUND: Adherence to a healthy diet could contribute to maintaining adequate health throughout the menopausal transition, but data are scarce. OBJECTIVE: We evaluated the association between menopausal status and changes in dietary intake in Swiss adult women. METHODS: Cross-sectional (n = 2439) and prospective analyses (n = 1656) were conducted between 2009 and 2012 (first follow-up) among women (mean age ± SD, 58.2 ± 10.5 y) living in Lausanne, Switzerland. In both visits, dietary intake was assessed using a validated FFQ, and menopausal status was classified based on the presence or absence of menstruations. Multivariable linear and logistic regression models were used to investigate the cross-sectional association of menopausal status (postmenopausal compared with premenopausal) at the first follow-up with food intake and dietary recommendations. To examine whether menopausal status (premenopausal as reference group, menopausal transition, and postmenopausal) during 5 y of follow-up was associated with longitudinal changes in diet, including adherence to dietary Swiss recommendations, we applied multivariable linear and logistic mixed models adjusted for several covariates. RESULTS: At the first follow-up, postmenopausal women consumed less (P < 0.002) meat [median (IQR) 57.2 (35-86.2) compared with 62.5 (41.2-95.2) g/d], pasta [61.8 (37.5-89.2) compared with 85 (57.8-128) g/d], and added sugar [0.1 (0-4) compared with 0.7 (0-8) g/d] and more dairy products [126 (65.4-214) compared with 109 (64.5-182) g/d] and fruit [217 (115-390) compared with 174 (83.2-319) g/d] than premenopausal women. However, linear regression analysis adjusted for potential confounding factors showed no independent (cross-sectional) associations of menopausal status with total energy intake (TEI) and individual macro- or micronutrient intakes. In the prospective analysis, compared with women who remained premenopausal during follow-up (n = 244), no differences were found in changes in TEI, dietary intakes, or adherence to the Swiss dietary recommendations in women transitioning from premenopausal to postmenopausal (n = 229) and who remained postmenopausal (n = 1168). CONCLUSION: The menopausal transition is not associated with changes in dietary habits among Swiss women.

Effect of fully automated closed-loop insulin delivery using faster aspart versus standard aspart on gluco-regulatory hormones in type 2 diabetes.

We retrospectively assessed gluco-regulatory hormones over 10 h (including two meals) of fully automated closed-loop insulin delivery using faster (FA) versus standard insulin aspart (IAsp) in adults with type 2 diabetes [n = 15, age 59 ± 10 years, body mass index 34.5 ± 9.1 kg/m2 , glycated haemoglobin 7.7 ± 1.2% (60 ± 13 mmol/mol)]. Plasma concentration of human insulin, IAsp, C-peptide, glucagon, glucagon-like peptide 1, glucose-dependent insulinotropic peptide and peptide tyrosine tyrosine were measured every 15-30 min. Endogenous insulin secretion was calculated using C-peptide deconvolution and exposures to hormones were compared using their mean plasma concentrations. Ten-hour exposure of IAsp was higher with FA versus IAsp (P = .037) in line with the 10% higher insulin requirements to achieve similar glucose control. No significant difference was found for total insulin exposure and endogenous insulin secretion. Similarly, other gluco-regulatory hormones did not significantly differ. In conclusion, the faster pharmacokinetic profile and slightly higher aspart exposure of FA versus IAsp remained without significant effects on endogenous insulin secretion or other gluco-regulatory hormones. Further studies are warranted to explore the metabolic and endocrine effects of novel insulins with accelerated pharmacokinetic properties.

Effect of nutrition on postprandial glucose control in hospitalized patients with type 2 diabetes receiving fully automated closed-loop insulin therapy.

Fully automated closed-loop insulin delivery may offer a novel way to manage diabetes in hospital. However, postprandial glycaemic control remains challenging. We aimed to assess the effect of nutritional intake on postprandial glucose control in hospitalized patients with type 2 diabetes receiving fully closed-loop insulin therapy. The effects of different meal types and macronutrient composition on sensor glucose time-in-target (TIT, 3.9-10.0 mmol/L) and mean sensor glucose were assessed with hierarchical linear models using a Bayesian estimation approach. TIT was lower and the mean sensor glucose slightly higher, after breakfast compared with lunch and dinner, whereas the insulin dose was higher. Across meals, when carbohydrates were replaced by fat, or to a lesser extent by protein, postprandial glucose control improved. For breakfast, a 3.9% improvement in TIT was observed when 10% of the energy from carbohydrates was replaced by fat. Improvements were slightly lower during lunch and dinner (3.2% and 3.4%) or when carbohydrates were replaced by protein (2.2 and 2.7%, respectively). We suggest that reducing carbohydrate at the expense of fat or protein, could further improve glucose control during fully closed-loop insulin therapy in hospital.