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.

Combined intake of caffeine and low-dose glucose to reduce exercise-related hypoglycaemia in individuals with type 1 diabetes on ultra-long-acting insulin degludec: A randomized, controlled, double-blind, cross-over trial.

AIM: To evaluate whether caffeine combined with a moderate amount of glucose reduces the risk for exercise-related hypoglycaemia compared with glucose alone or control in adult people with type 1 diabetes using ultra-long-acting insulin degludec. MATERIALS AND METHODS: Sixteen participants conducted three aerobic exercise sessions (maximum 75 min) in a randomized, double-blind, cross-over design. Thirty minutes before exercise, participants ingested a drink containing either 250 mg of caffeine + 10 g of glucose + aspartame (CAF), 10 g of glucose + aspartame (GLU), or aspartame alone (ASP). The primary outcome was time to hypoglycaemia. RESULTS: There was a significant effect of the condition on time to hypoglycaemia (χ2 = 7.674, p = .0216). Pairwise comparisons revealed an 85.7% risk reduction of hypoglycaemia for CAF compared with ASP (p = .044). No difference was observed between GLU and ASP (p = .104) or between CAF and GLU (p = .77). While CAF increased glucose levels during exercise compared with GLU and ASP (8.3 ± 1.9 mmol/L vs. 7.7 ± 2.2 mmol/L vs. 5.8 ± 1.4 mmol/L; p < .001), peak plasma glucose levels during exercise did not differ between CAF and GLU (9.3 ± 1.4 mmol/L and 9.1 ± 1.6 mmol/L, p = .80), but were higher than in ASP (6.6 ± 1.1 mmol/L; p < .001). The difference in glucose levels between CAF and GLU was largest during the last 15 min of exercise (p = .002). Compared with GLU, CAF lowered perceived exertion (p = .023). CONCLUSIONS: Pre-exercise caffeine ingestion combined with a low dose of glucose reduced exercise-related hypoglycaemia compared with control while avoiding hyperglycaemia.

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.

A rib-sparing unilateral transpedicular thoracic corpectomy using the ultrasonic bone scalpel: a novel technique and pictorial guide.

BACKGROUND: The thoracic corpectomy is a well-described technique for the surgical treatment of vertebral column fractures with spinal canal compromise. Traditionally, the posterolateral approach to this procedure required the removal of the approach side rib in order to introduce the corpectomy cage. This rib removal, however, has been identified as a major contributor to post-operative morbidity. Rib-sparing techniques have been shown to be beneficial in minimizing post-operative morbidity in non-spinal surgeries. Herein, we present a previously undescribed technique of a rib-sparing thoracic corpectomy that avoids sequalae of rib resection with assistance from an ultrasonic bone scalpel (UBS). METHODS: A retrospective chart review was conducted on patients having undergone this thoracic corpectomy technique. Data on patient age at operation, indication for surgery, number of corpectomies per case, estimated blood loss (EBL), operative time (OT), intra-operative complications, and post-operative length of stay (LOS) were collected and analyzed. A pictorial step-by-step guide was created to highlight the advantages of an entirely posterior rib-sparing unilateral transpedicular technique for thoracic corpectomy. RESULTS: A total of 36 corpectomies were performed on 32 patients between August 2015 and March 2023. Patients ages ranged from 17 to 85 years (mean = 63). The most common indication was oncological (n = 22, 69%), followed by degenerative/traumatic deformity (n = 7, 22%), and infection (n = 3, 9%). For the cases for which data was accessible, mean EBL was 853 cc and mean OT was 178 min. The average post-operative LOS was 6.5 days. CONCLUSION: The described surgical approach makes it possible to create a transpedicular corridor with no costectomy for implantation of an expandable titanium cage and anterior column reconstruction. The use of the UBS in this approach is critical as it minimizes bony removal and avoids sequelae of rib resection. The described technique has the potential to circumvent post-costectomy pain, thereby expediting post-operative recovery after thoracic corpectomy.

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.

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.

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.

Day-to-day variability of insulin requirements in the inpatient setting: Observations during fully closed-loop insulin delivery.

The aim of this study was to characterize the variability of exogenous insulin requirements during fully closed-loop insulin delivery in hospitalized patients with type 2 diabetes or new-onset hyperglycaemia, and to determine patient-related characteristics associated with higher variability of insulin requirements. We retrospectively analysed data from two fully closed-loop inpatient studies involving adults with type 2 diabetes or new-onset hyperglycaemia requiring insulin therapy. The coefficient of variation quantified day-to-day variability of exogenous insulin requirements during up to 15 days using fully automated closed-loop insulin delivery. Data from 535 days in 67 participants were analysed. The coefficient of variation of day-to-day exogenous insulin requirements was 30% ± 16%, and was higher between nights than between any daytime period (56% ± 29% overnight [11:00 pm to 4:59 am] compared with 41% ± 21% in the morning [5:00 am to 10:59 am], 39% ± 15% in the afternoon [11:00 am to 4:59 pm] and 45% ± 19% during the evening [5:00 pm to 10:59 pm]; all P < 0.01). There is high day-to-day variability of exogenous insulin requirements in inpatients, particularly overnight, and diabetes management approaches should account for this variability.

The impact of postbariatric hypoglycaemia on driving performance: A randomized, single-blind, two-period, crossover study in a driving simulator.

Postbariatric hypoglycaemia (PBH) is an increasingly recognized complication of bariatric surgery, but its effect on daily functioning remains unclear. In this randomized, single-blind, crossover trial we assessed driving performance in patients with PBH. Ten active drivers with PBH (eight females, age 38.2 ± 14.7 years, body mass index 27.2 ± 4.6 kg/m2 ) received 75 g glucose to induce PBH in the late postprandial period and aspartame to leave glycaemia unchanged, on two different occasions. A simulator was driven during 10 minutes before (D0) and 20 (D1), 80 (D2), 125 (D3) and 140 minutes (D4) after the glucose/aspartame ingestion, reflecting the expected blood glucose (BG) increase (D1), decrease (D2) and hypoglycaemia (D3, D4). Seven driving features indicating impaired driving were integrated in a Bayesian hierarchical regression model to assess the difference in driving performance after glucose/aspartame ingestion. Mean ± standard deviation peak and nadir BG after glucose were 182 ± 24 and 47 ± 14 mg/dL, while BG was stable after aspartame (85 ± 4 mg/dL). Despite the lack of a difference in symptom perception, driving performance was significantly impaired after glucose versus aspartame during D4 (posterior probability 98.2%). Our findings suggest that PBH negatively affects driving performance.

Hybrid closed-loop glucose control with faster insulin aspart compared with standard insulin aspart in adults with type 1 diabetes: A double-blind, multicentre, multinational, randomized, crossover study.

AIM: To evaluate the use of hybrid closed-loop glucose control with faster-acting insulin aspart (Fiasp) in adults with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: In a double-blind, multinational, randomized, crossover study, 25 adults with T1D using insulin pump therapy (mean ± SD, age 38 ± 9 years, HbA1c 7.4% ± 0.8% [57 ± 8 mmol/mol]) underwent two 8-week periods of unrestricted living comparing hybrid closed-loop with Fiasp and hybrid closed-loop with standard insulin aspart in random order. During both interventions the CamAPS FX closed-loop system incorporating the Cambridge model predictive control algorithm was used. RESULTS: In an intention-to-treat analysis, the proportion of time sensor glucose was in the target range (3.9-10.0 mmol/L; primary endpoint) was not different between interventions (75% ± 8% vs. 75% ± 8% for hybrid closed-loop with Fiasp vs. hybrid closed-loop with standard insulin aspart; mean-adjusted difference -0.6% [95% CI -1.8% to 0.7%]; p < .001 for non-inferiority [non-inferiority margin 5%]). The proportion of time with sensor glucose less than 3.9 mmol/L (median [IQR] 2.4% [1.2%-3.2%] vs. 2.9% [1.7%-4.0%]; p = .01) and less than 3.0 mmol/L (median [IQR] 0.4% [0.2%-0.7%] vs. 0.7% [0.2%-0.9%]; p = .03) was reduced with Fiasp versus standard insulin aspart. There was no difference in mean glucose (8.1 ± 0.8 vs. 8.0 ± 0.8 mmol/L; p = .13) or glucose variability (SD of sensor glucose 2.9 ± 0.5 vs. 2.9 ± 0.5 mmol/L; p = .90). Total daily insulin requirements did not differ (49 ± 15 vs. 49 ± 15 units/day; p = .45). No severe hypoglycaemia or ketoacidosis occurred. CONCLUSIONS: The use of Fiasp in the CamAPS FX closed-loop system may reduce hypoglycaemia without compromising glucose control compared with standard insulin aspart in adults with T1D.

Performance of a factory-calibrated, real-time continuous glucose monitoring system during elective abdominal surgery.

We assessed the performance of the factory-calibrated, sixth-generation continuous glucose monitoring (CGM) system Dexcom G6® (DexCom Inc., San Diego, California) during elective abdominal surgery. Twenty adults with (pre)diabetes undergoing abdominal surgery (>2 hours; 15 men, age 69 ± 13 years, glycated haemoglobin 53 ± 14 mmol/mol) wore the sensor from 1 week prior to surgery until hospital discharge. From induction of anaesthesia until 2 hours post-surgery, reference capillary glucose values were obtained every 20 minutes using the Accu-Chek® Inform II meter (Roche Diabetes Care, Mannheim, Germany). The primary endpoint was the mean absolute relative difference (ARD) between sensor and reference method during this period. In total, 1207 CGM/reference pairs were obtained. In the peri-operative period (523 pairs), mean ± SD and median (interquartile range [IQR]) ARD were 12.7% ± 8.7% and 9.9 (6.3;15.9)%, respectively, and 67.4% of sensor readings were within International Organization of Standardization 15197:2013 limits. CGM overestimated reference glucose by 1.1 ± 0.8 mmol/L (95% limits of agreement -0.5;2.7 mmol/L). Clarke error grid zones A or B contained 99.2% of pairs (A: 78.8%; B: 20.4%). The median (IQR) peri-operative sensor availability was 98.6 (95.9;100.0)%. No clinically significant adverse events occurred. In conclusion, the Dexcom G6 device showed consistent and acceptable accuracy during elective abdominal surgery, opening new avenues for peri-operative glucose management.

[Closed-loop systems - Update 2020]. / Closed-loop-Systeme ­ Update 2020.

Closed-loop systems - Update 2020 Abstract. The artificial pancreas (also referred to as a Closed-loop system) represents the latest development in diabetes therapy. Closed-loop systems autonomously direct subcutaneous insulin infusion via a control algorithm based on real-time continuous glucose monitoring. Closed-loop systems have been tested in clinical studies since 2011, and were shown to improve glucose control by reducing hyper- and hypoglycaemia as well as glucose variability when compared with conventional insulin pump therapy. In 2016, the US regulatory authority approved the first hybrid-closed-loop system for the treatment of type 1 diabetes. Hybrid-closed loop systems are not yet fully automated and still require the user to be actively involved for insulin dosing at mealtimes. In spite of the remarkable progress, the delayed action profile of subcutaneously administered insulin and the need to wear multiple devices on the body remain challenging. The present review article summarizes the current state of the art of closed-loop systems in diabetes care and will address technical aspects, evidence from clinical studies as well as future developments in the field.

Short-term fully closed-loop insulin delivery using faster insulin aspart compared with standard insulin aspart in type 2 diabetes.

We evaluated the efficacy and safety of short-term fully closed-loop insulin delivery using faster versus standard insulin aspart in type 2 diabetes. Fifteen adults with insulin-treated type 2 diabetes underwent 22 hours of closed-loop insulin delivery with either faster or standard insulin aspart in a double-blind randomized crossover design. Basal-bolus regimen was replaced by model predictive control algorithm-directed insulin delivery based on sensor glucose levels. The primary outcome was time with plasma glucose in target range (5.6-10.0 mmol/L) and did not differ between treatments (mean difference [95% CI] 3.3% [-8.2; 1.7], P = 0.17). Mean glucose and glucose variability were comparable, as was time spent below and above target range. Hypoglycaemia (<3.5 mmol/L) occurred once with faster insulin aspart and twice with standard insulin aspart. Mean total insulin dose was higher with faster insulin aspart (mean difference [95% CI] 3.7 U [0.7; 6.8], P = 0.021). No episodes of severe hypoglycaemia or other serious adverse events occurred. In conclusion, short-term fully closed-loop in type 2 diabetes may require higher dose of faster insulin aspart compared with standard insulin aspart to achieve comparable glucose control.