Risk factors at admission of in-hospital dysglycemia, mortality, and readmissions in patients with type 2 diabetes and pneumonia.

AIMS: In-hospital dysglycemia is associated with adverse outcomes. Identifying patients at risk of in-hospital dysglycemia early on admission may improve patient outcomes. METHODS: We analysed 117 inpatients admitted with pneumonia and type 2 diabetes monitored by continuous glucose monitoring. We assessed potential risk factors for in-hospital dysglycemia and adverse clinical outcomes. RESULTS: Time in range (3.9-10.0 mmol/l) decreased by 2.9 %-points [95 % CI 0.7-5.0] per 5 mmol/mol [2.6 %] increase in admission haemoglobin A1c, 16.2 %-points if admission diabetes therapy included insulin therapy [95 % CI 2.9-29.5], and 2.4 %-points [95 % CI 0.3-4.6] per increase in the Charlson Comorbidity Index (CCI) (integer, as a measure of severity and amount of comorbidities). Thirty-day readmission rate increased with an IRR of 1.24 [95 % CI 1.06-1.45] per increase in CCI. In-hospital mortality risk increased with an OR of 1.41 [95 % CI 1.07-1.87] per increase in Early Warning Score (EWS) (integer, as a measure of acute illness) at admission. CONCLUSIONS: Dysglycemia among hospitalised patients with pneumonia and type 2 diabetes was associated with high haemoglobin A1c, insulin treatment before admission, and the amount and severity of comorbidities (i.e., CCI). Thirty-day readmission rate increased with high CCI. The risk of in-hospital mortality increased with the degree of acute illness (i.e., high EWS) at admission. Clinical outcomes were independent of chronic glycemic status, i.e. HbA1c, and in-hospital glycemic status.

Screen Media Use and Mental Health of Children and Adolescents: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Excessive screen media use has been associated with poorer mental health among children and adolescents in several observational studies. However, experimental evidence supporting this hypothesis is lacking. Objective: To investigate the effects of a 2-week screen media reduction intervention on children's and adolescents' mental health. Design, Setting, and Participants: This prespecified secondary analysis of a cluster randomized clinical trial with a 2-week follow-up included 89 families (with 181 children and adolescents) from 10 Danish municipalities in the region of Southern Denmark. All study procedures were carried out in the home of the participants. Enrollment began on June 6, 2019, and ended on March 30, 2021. This analysis was conducted between January 1 and November 30, 2023. Intervention: Families were randomly allocated to a screen media reduction group or a control group. The 2-week screen media reduction intervention was designed to ensure a high level of compliance to the reduction in leisure-time screen media use. Participants allocated to the intervention group had to reduce their leisure-time screen media use to 3 hours per week or less per person and hand over smartphones and tablets. Main Outcomes and Measures: The main outcome was the between-group mean difference in change in total behavioral difficulties, measured by the Strengths and Difficulties Questionnaire at 2-week follow-up. Results were estimated using mixed-effects tobit regression models. Analyses were carried out as both intention to treat and complete case. Results: In the sample of 89 families including 181 children and adolescents (intervention group [45 families]: 86 children; mean [SD] age, 8.6 [2.7] years; 42 girls [49%]; control group [44 families]: 95 children; mean [SD] age, 9.5 [2.5] years; 57 girls [60%]), there was a statistically significant between-group mean difference in the total difficulties score, favoring the screen media reduction intervention (-1.67; 95% CI, -2.68 to -0.67; Cohen d, 0.53). The greatest improvements were observed for internalizing symptoms (emotional symptoms and peer problems; between-group mean difference, -1.03; 95% CI, -1.76 to -0.29) and prosocial behavior (between-group mean difference, 0.84; 95% CI, 0.39-1.30). Conclusions and Relevance: This secondary analysis of a randomized clinical trial found that a short-term reduction in leisure-time screen media use within families positively affected psychological symptoms of children and adolescents, particularly by mitigating internalizing behavioral issues and enhancing prosocial behavior. More research is needed to confirm whether these effects are sustainable in the long term. Trial Registration: ClinicalTrials.gov Identifier: NCT04098913.

Factors Influencing Physical Activity Level in Adults With Type 1 Diabetes: A Cross-sectional Study.

OBJECTIVES: Exercise is a recommended component of type 1 diabetes (T1D) treatment because high physical activity levels improve health outcomes. However, many people with T1D do not meet physical activity recommendations. Our aim in this study was to identify factors influencing physical activity levels in people with T1D. METHODS: This questionnaire-based study included adults with T1D from 1 outpatient clinic in the United Kingdom and 2 clinics in Denmark. Exercise characteristics, motivators, and barriers were assessed. Physical activity level was measured using the Saltin-Grimby Physical Activity Level Scale. Respondents were categorized into 3 activity groups: inactive, light active, and moderate-to-vigourous active. RESULTS: Of the 332 respondents, 8.4% rated themselves as inactive, 48% as light active, and 43% as moderate-to-vigourous active. Seventy-eight percent of inactive and light active repondents expressed a desire to become more physically active. Fifty-three percent of respondents had received guidance concerning exercise/physical activity from their diabetes team. Being male and having received guidance were associated with a higher physical activity level. The major motivators for exercising/being physically active were improved mental and physical health and glycemic control, whereas the most frequent barriers were busyness with work/private life and lack of motivation. Worries about glucose excursions, costs, lack of knowledge, and health-related reasons were more prevalent barriers in the least active groups. CONCLUSIONS: This study demonstrated that 78% of inactive and light active respondents reported wishing to become more physically active. Receiving guidance about exercise/physical activity was associated with a higher physical activity level, but only 53% of respondents had received support from their diabetes team.

Healthcare professionals' competencies and confidence in managing hospitalized patients with type 2 diabetes.

AIMS: In hospitals, 15%-20% of patients have diabetes. Therefore, all healthcare professionals (HCPs) must have a basic knowledge of in-hospital diabetes management. This survey assessed the knowledge of diabetes among HCPs in Denmark. METHODS: A 27-item questionnaire was developed and reviewed independently before the survey was distributed. The questionnaire contained seven baseline questions on the HCPs' current workplace, educational level, usual shift routines and years of experience, 18 multiple-choice questions and 2 cases. RESULTS: A total of 252 completed questionnaires were returned by 133 (52.8%) physicians, 101 (40.1%) nurses and 18 (7.1%) healthcare assistants. HCPs answered 50% of the questions correctly. Having experience from endocrinological departments increased the correct response score (0%-100%) by 6.2% points (95% CI 0.3-12.1) (p = 0.039) and 3.1% points (95% CI 1.5-4.7) for every increase in confidence level on a scale from 1 to 10 (p < 0.001). HCPs scored 8 out of 10 on a confidence level scale on average. In a fictive case, 50% of HCPs administered the correct bolus insulin dose. Hyperglycaemia (>10.0 mmol/L) and hypoglycaemia (<3.9 mmol/L) were correctly identified by around 40% of HCPs. Hypoglycaemia was rated more important than hyperglycaemia by most HCPs. CONCLUSION: Significant gaps in identifying hypo- and hyperglycaemia and correct administration of bolus insulin have been identified, which could be targeted in future education for HCPs. HCPs answered 50% of questions related to in-hospital diabetes management correctly. Experience from endocrinological departments and self-rated confidence levels are associated with HCPs' in-hospital diabetes competencies.

Protein Binder Toolbox for Studies of Solute Carrier Transporters.

Transporters of the solute carrier superfamily (SLCs) are responsible for the transmembrane traffic of the majority of chemical substances in cells and tissues and are therefore of fundamental biological importance. As is often the case with membrane proteins that can be heavily glycosylated, a lack of reliable high-affinity binders hinders their functional analysis. Purifying and reconstituting transmembrane proteins in their lipidic environments remains challenging and standard approaches to generate binders for multi-transmembrane proteins, such as SLCs, channels or G protein-coupled receptors (GPCRs) are lacking. While generating protein binders to 27 SLCs, we produced full length protein or cell lines as input material for binder generation by selected binder generation platforms. As a result, we obtained 525 binders for 22 SLCs. We validated the binders with a cell-based validation workflow using immunofluorescent and immunoprecipitation methods to process all obtained binders. Finally, we demonstrated the potential applications of the binders that passed our validation pipeline in structural, biochemical, and biological applications using the exemplary protein SLC12A6, an ion transporter relevant in human disease. With this work, we were able to generate easily renewable and highly specific binders against SLCs, which will greatly facilitate the study of this neglected protein family. We hope that the process will serve as blueprint for the generation of binders against the entire superfamily of SLC transporters.

Inflammatory and endothelial host responses in community-acquired pneumonia: exploring the relationships with HbA1c, admission plasma glucose, and glycaemic gap-a cross-sectional study.

Introduction: Diabetes is associated with dysregulated immune function and impaired cytokine release, while transient acute hyperglycaemia has been shown to enhance inflammatory cytokine release in preclinical studies. Although diabetes and acute hyperglycaemia are common among patients with community-acquired pneumonia (CAP), the impact of chronic, acute, and acute-on-chronic hyperglycaemia on the host response within this population remains poorly understood. This study investigated whether chronic, acute, and acute-on- chronic hyperglycaemia are associated with distinct mediators of inflammatory, endothelial, and angiogenic host response pathways in patients with CAP. Methods: In a cross-sectional study of 555 patients with CAP, HbA1c, admission plasma (p)-glucose, and the glycaemic gap (admission p-glucose minus HbA1c- derived average p-glucose) were employed as measures of chronic, acute, and acute-on-chronic hyperglycaemia, respectively. Linear regression was used to model the associations between the hyperglycaemia measures and 47 proteins involved in inflammation, endothelial activation, and angiogenesis measured at admission. The models were adjusted for age, sex, CAP severity, pathogen, immunosuppression, comorbidity, and body mass index. Adjustments for multiple testing were performed with a false discovery rate threshold of less than 0.05. Results: The analyses showed that HbA1c levels were positively associated with IL-8, IL-15, IL-17A/F, IL-1RA, sFlt-1, and VEGF-C. Admission plasma glucose was also positively associated with these proteins and GM-CSF. The glycaemic gap was positively associated with IL-8, IL-15, IL-17A/F, IL-2, and VEGF-C. Conclusion: In conclusion, chronic, acute, and acute-on-chronic hyperglycaemia were positively associated with similar host response mediators. Furthermore, acute and acute-on-chronic hyperglycaemia had unique associations with the inflammatory pathways involving GM-CSF and IL-2, respectively.

Impact of a nationwide school policy on body mass index in Danish school children: An interrupted time series analysis.

Objectives: A new school policy mandating 45 min physical activity daily during school was introduced in Denmark in 2014. We aimed to evaluate the effect of this policy on BMI in school-aged children. It was hypothesized that the school policy would decrease BMI, especially in the obese fraction of the population (90th percentile BMI). Study design: This register-based study was conducted as a natural experiment. Methods: Analyses were based on data from The National Child Health Register that contains nationwide data on height and weight from mandatory preventive health examinations completed by school nurses or medical doctors during pre-preparatory classes (0th-3rd grade) and lower secondary education (7th-9th grade). A total of 401,517 children were included in the analyses with annual repeated cross-sectional data covering the period from 2012 to 2018. The effect of the school policy was evaluated using an interrupted time series approach comparing pre- and post-policy slopes in BMI, stratified by sex and age-group. Results: In boys, no significant differences were observed in mean BMI slopes from pre-to post-policy in either age-group. In girls, post-policy slopes were significantly higher compared to pre-policy in both age-groups (0th-3rd grade: ß:0·034 kg/m2, 95%-CI: (0·024; 0·043), p-value: <0·001; 7th-9th grade: ß:0·066 kg/m2, 95%-CI: (0·028; 0·103), p-value: 0·001). No significant differences in slopes were observed in BMI at the 90th percentile from pre-to post-policy for both sexes and across both age-groups. Adjustment for leisure-time physical activity as a potential time-varying confounder did not alter the findings. Conclusions: In conclusion, we did not detect a significant decrease in BMI levels among school-aged children following the introduction of a nationwide school policy specifying daily physical activity in school. If anything, a small positive change in BMI was observed in girls. More research is needed to understand whether structural changes similar to this requirement are able to prevent overweight and obesity in children and adolescents.

Simulation of functional additive and non-additive genetic effects using statistical estimates from quantitative genetic models.

Stochastic simulation software is commonly used to aid breeders designing cost-effective breeding programs and to validate statistical models used in genetic evaluation. An essential feature of the software is the ability to simulate populations with desired genetic and non-genetic parameters. However, this feature often fails when non-additive effects due to dominance or epistasis are modeled, as the desired properties of simulated populations are estimated from classical quantitative genetic statistical models formulated at the population level. The software simulates underlying functional effects for genotypic values at the individual level, which are not necessarily the same as effects from statistical models in which dominance and epistasis are included. This paper provides the theoretical basis and mathematical formulas for the transformation between functional and statistical effects in such simulations. The transformation is demonstrated with two statistical models analyzing individual phenotypes in a single population (common in animal breeding) and plot phenotypes of three-way hybrids involving two inbred populations (observed in some crop breeding programs). We also describe different methods for the simulation of functional effects for additive genetics, dominance, and epistasis to achieve the desired levels of variance components in classical statistical models used in quantitative genetics.

Association between recent exposure to continuous glucose monitoring-recorded hypoglycaemia and counterregulatory and symptom responses to subsequent controlled hypoglycaemia in people with type 1 diabetes.

AIM: Experimental hypoglycaemia blunts the counterregulatory hormone and symptom responses to a subsequent episode of hypoglycaemia. In this study, we aimed to assess the associations between antecedent exposure and continuous glucose monitoring (CGM)-recorded hypoglycaemia during a 1-week period and the counterregulatory responses to subsequent experimental hypoglycaemia in people with type 1 diabetes. MATERIALS AND METHODS: Forty-two people with type 1 diabetes (20 females, mean ± SD glycated haemoglobin 7.8% ± 1.0%, diabetes duration median (interquartile range) 22.0 (10.5-34.9) years, 29 CGM users, and 19 with impaired awareness of hypoglycaemia) wore an open intermittently scanned CGM for 1 week to detect hypoglycaemic exposure before a standardized hyperinsulinaemic-hypoglycaemic [2.8 ± 0.1 mmol/L (50.2 ± 2.3 mg/dl)] glucose clamp. Symptom responses and counterregulatory hormones were measured during the clamp. The study is part of the HypoRESOLVE project. RESULTS: CGM-recorded hypoglycaemia in the week before the clamp was negatively associated with adrenaline response [ß -0.09, 95% CI (-0.16, -0.02) nmol/L, p = .014], after adjusting for CGM use, awareness of hypoglycaemia, glycated haemoglobin and total daily insulin dose. This was driven by level 2 hypoglycaemia [<3.0 mmol/L (54 mg/dl)] [ß -0.21, 95% CI (-0.41, -0.01) nmol/L, p = .034]. CGM-recorded hypoglycaemia was negatively associated with total, autonomic, and neuroglycopenic symptom responses, but these associations were lost after adjusting for potential confounders. CONCLUSIONS: Recent exposure to CGM-detected hypoglycaemia was independently associated with an attenuated adrenaline response to experimental hypoglycaemia in people with type 1 diabetes.

Summary of clinical investigation plan for The DIATEC trial: in-hospital diabetes management by a diabetes team and continuous glucose monitoring or point of care glucose testing - a randomised controlled trial.

BACKGROUND: Worldwide, up to 20 % of hospitalised patients have diabetes mellitus. In-hospital dysglycaemia increases patient mortality, morbidity, and length of hospital stay. Improved in-hospital diabetes management strategies are needed. The DIATEC trial investigates the effects of an in-hospital diabetes team and operational insulin titration algorithms based on either continuous glucose monitoring (CGM) data or standard point-of-care (POC) glucose testing. METHODS: This is a two-armed, two-site, prospective randomised open-label blinded endpoint (PROBE) trial. We recruit non-critically ill hospitalised general medical and orthopaedic patients with type 2 diabetes treated with basal, prandial, and correctional insulin (N = 166). In both arms, patients are monitored by POC glucose testing and diabetes management is done by ward nurses guided by in-hospital diabetes teams. In one of the arms, patients are monitored in addition to POC glucose testing by telemetric CGM viewed by the in-hospital diabetes teams only. The in-hospital diabetes teams have operational algorithms to titrate insulin in both arms. Outcomes are in-hospital glycaemic and clinical outcomes. DISCUSSION: The DIATEC trial will show the glycaemic and clinical effects of in-hospital CGM handled by in-hospital diabetes teams with access to operational insulin titration algorithms in non-critically ill patients with type 2 diabetes. The DIATEC trial seeks to identify which hospitalised patients will benefit from CGM and in-hospital diabetes teams compared to POC glucose testing. This is essential information to optimise the use of healthcare resources before broadly implementing in-hospital CGM and diabetes teams. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov with identification number NCT05803473 on March 27th 2023.

Corrigendum: Adiponectin as a predictor of mortality and readmission in patients with community-acquired pneumonia: a prospective cohort study.

[This corrects the article DOI: 10.3389/fmed.2024.1329417.].

Effectiveness of a Preschool Motor Skill Intervention on Body Mass Index and Movement Behavior: 6-, 18-, and 30-Month Findings From a Cluster Randomized Controlled Trial.

PURPOSE: To study the effectiveness of a preschool staff-delivered motor skills intervention on body composition and physical activity over a 2.5-year time frame. METHODS: In this pragmatic parallel cluster randomized controlled trial (16 preschools), outcome data were collected after 6 (body composition only), 18, and 30 months of intervention. The main physical activity outcomes were accelerometer behavior measures summarizing the total percentage of child daily movement (walk, run, cycle, and standing that included minor movements) and preschool movement during preschool attendance. To estimate between-group mean differences in outcomes, mixed-linear regression analyses including baseline value of the selected outcome and a treatment × time interaction term as a fixed effect were applied. In addition, the baseline preschool and child were included as a random effect. RESULTS: For body mass index, a total of 437 children (90%) had at least one valid baseline and one follow-up assessment. The corresponding numbers for preschool movement and daily movement were 163 (55%) and 146 (49%), respectively. No significant between-group mean difference was identified for body mass index, waist-to-height ratio, or any physical activity outcomes. CONCLUSION: Overall, this preschool motor skills intervention had no effect on either child anthropometry or physical activity, consistent with previous studies.

Water Promotes Melting of a Metal-Organic Framework.

Water is one of the most reactive and abundant molecules on Earth, and it is thus crucial to understand its reactivity with various material families. One of the big unknown questions is how water in liquid and vapor forms impact the fast-emerging class of metal-organic frameworks (MOFs). Here, we discover that high-pressure water vapor drastically modifies the structure and hence the dynamic, thermodynamic, and mechanical properties of MOF glasses. In detail, we find that an archetypical MOF (ZIF-62) is extremely sensitive to heat treatments performed at 460 °C and water vapor pressures up to ∼110 bar. Both the melting and glass transition temperatures decrease remarkably (by >100 °C), and simultaneously, hardness and Young's modulus increase by up to 100% under very mild treatment conditions (<20 bar of hydrothermal pressure). Structural analyses suggest water to partially coordinate to Zn in the form of a hydroxide ion by replacing a bridging imidazolate-based linker. The work provides insight into the role of hot-compressed water in influencing the structure and properties of MOF glasses and opens a new route for systematically changing the thermodynamics and kinetics of MOF liquids and thus altering the thermal and mechanical properties of the resulting MOF glasses.

Adiponectin as a predictor of mortality and readmission in patients with community-acquired pneumonia: a prospective cohort study.

Background: Adiponectin is secreted by adipocytes and is inversely associated with obesity. Given the association between low body mass index (BMI) and higher mortality risk after community-acquired pneumonia (CAP), we hypothesized that high adiponectin levels are associated with a higher risk of adverse clinical outcomes in patients with CAP. Methods: In a prospective cohort study of 502 patients hospitalized with CAP, adiponectin was measured in serum at admission. The associations between adiponectin and clinical outcomes were estimated with logistic regression analyses adjusted for age, sex, and measures of obesity (BMI, waist circumference or body fat percentage). Results: Adiponectin was associated with higher 90-day mortality for each 1 µg/mL increase [OR 1.02, 95% CI (1.00, 1.04), p = 0.048] independent of age and sex. Likewise, adiponectin was associated with a higher risk of 90-day readmission for each 1 µg/mL increase [OR 1.02, 95% CI (1.01, 1.04), p = 0.007] independent of age and sex. The association between adiponectin and 90-day mortality disappeared, while the association with 90-day readmission remained after adjusting for adiposity. Conclusion: Adiponectin was positively associated with mortality and readmission. The association with mortality depended on low body fat, whereas the association with readmission risk was independent of obesity.

Facilitating ambulatory heart rate variability analysis using accelerometry-based classifications of body position and self-reported sleep.

Objective.This study aimed to examine differences in heart rate variability (HRV) across accelerometer-derived position, self-reported sleep, and different summary measures (sleep, 24 h HRV) in free-living settings using open-source methodology.Approach.HRV is a biomarker of autonomic activity. As it is strongly affected by factors such as physical behaviour, stress, and sleep, ambulatory HRV analysis is challenging. Beat-to-beat heart rate (HR) and accelerometry data were collected using single-lead electrocardiography and trunk- and thigh-worn accelerometers among 160 adults participating in the SCREENS trial. HR files were processed and analysed in the RHRV R package. Start time and duration spent in physical behaviours were extracted, and time and frequency analysis for each episode was performed. Differences in HRV estimates across activities were compared using linear mixed models adjusted for age and sex with subject ID as random effect. Next, repeated-measures Bland-Altman analysis was used to compare 24 h RMSSD estimates to HRV during self-reported sleep. Sensitivity analyses evaluated the accuracy of the methodology, and the approach of employing accelerometer-determined episodes to examine activity-independent HRV was described.Main results.HRV was estimated for 31 289 episodes in 160 individuals (53.1% female) at a mean age of 41.4 years. Significant differences in HR and most markers of HRV were found across positions [Mean differences RMSSD: Sitting (Reference) - Standing (-2.63 ms) or Lying (4.53 ms)]. Moreover, ambulatory HRV differed significantly across sleep status, and poor agreement between 24 h estimates compared to sleep HRV was detected. Sensitivity analyses confirmed that removing the first and last 30 s of accelerometry-determined HR episodes was an accurate strategy to account for orthostatic effects.Significance.Ambulatory HRV differed significantly across accelerometry-assigned positions and sleep. The proposed approach for free-living HRV analysis may be an effective strategy to remove confounding by physical activity when the aim is to monitor general autonomic stress.

Incidental [18F]FDG-avid focuses in parotid glands on PET/CT.

BACKGROUND: The number of unexpected focal [18F]FDG-avid findings (incidentalomas) within the parotid gland (PGI) continues to increase with the expanding use of PET/CT scanning. The prevalence of malignancy in PGIs is uncertain and appropriate management is unsettled. AIMS: We aimed to explore the underlying pathologies associated with PGI. MATERIALS AND METHODS: A retrospective review of all patients with parotid gland incidentaloma(s) treated at the Ear-Nose-Throat Department, Aarhus University Hospital, Denmark in the period 2012-2021, was performed. RESULTS: In total, 94 patients with one (n = 86) or two (n = 8) PGI(s) were included. In patients with one PGI, 72 (84%) focuses were benign, two (2%) focuses were malignant (both malignant melanoma metastases), and 12 (14%) focuses were undiagnosed. In patients with two PGIs, all 12 lesions with pathological examinations were benign (4 PGIs were undiagnosed). The median SUVmax found in benign lesions was higher (12.0) compared to malignant lesions (5.5) (p = .043). CONCLUSIONS AND SIGNIFICANCE: The prevalence of malignancy was low (2/94, 2.4%) in PGIs. Based on our findings, PGI in patients without a history of parotid malignancy, who undergo PET/CT scanning for reasons other than head and neck cancer (including malignant melanoma), may be managed similarly to patients with asymptomatic parotid gland tumors.

Design and engineering of bispecific antibodies: insights and practical considerations.

Bispecific antibodies (bsAbs) have attracted significant attention due to their dual binding activity, which permits simultaneous targeting of antigens and synergistic binding effects beyond what can be obtained even with combinations of conventional monospecific antibodies. Despite the tremendous therapeutic potential, the design and construction of bsAbs are often hampered by practical issues arising from the increased structural complexity as compared to conventional monospecific antibodies. The issues are diverse in nature, spanning from decreased biophysical stability from fusion of exogenous antigen-binding domains to antibody chain mispairing leading to formation of antibody-related impurities that are very difficult to remove. The added complexity requires judicious design considerations as well as extensive molecular engineering to ensure formation of high quality bsAbs with the intended mode of action and favorable drug-like qualities. In this review, we highlight and summarize some of the key considerations in design of bsAbs as well as state-of-the-art engineering principles that can be applied in efficient construction of bsAbs with diverse molecular formats.

Counterregulatory hormone and symptom responses to hypoglycaemia in people with type 1 diabetes, insulin-treated type 2 diabetes or without diabetes: the Hypo-RESOLVE hypoglycaemic clamp study.

AIM: The sympathetic nervous and hormonal counterregulatory responses to hypoglycaemia differ between people with type 1 and type 2 diabetes and may change along the course of diabetes, but have not been directly compared. We aimed to compare counterregulatory hormone and symptom responses to hypoglycaemia between people with type 1 diabetes, insulin-treated type 2 diabetes and controls without diabetes, using a standardised hyperinsulinaemic-hypoglycaemic clamp. MATERIALS: We included 47 people with type 1 diabetes, 15 with insulin-treated type 2 diabetes, and 32 controls without diabetes. Controls were matched according to age and sex to the people with type 1 diabetes or with type 2 diabetes. All participants underwent a hyperinsulinaemic-euglycaemic-(5.2 ± 0.4 mmol/L)-hypoglycaemic-(2.8 ± 0.13 mmol/L)-clamp. RESULTS: The glucagon response was lower in people with type 1 diabetes (9.4 ± 0.8 pmol/L, 8.0 [7.0-10.0]) compared to type 2 diabetes (23.7 ± 3.7 pmol/L, 18.0 [12.0-28.0], p < 0.001) and controls (30.6 ± 4.7, 25.5 [17.8-35.8] pmol/L, p < 0.001). The adrenaline response was lower in type 1 diabetes (1.7 ± 0.2, 1.6 [1.3-5.2] nmol/L) compared to type 2 diabetes (3.4 ± 0.7, 2.6 [1.3-5.2] nmol/L, p = 0.001) and controls (2.7 ± 0.4, 2.8 [1.4-3.9] nmol/L, p = 0.012). Growth hormone was lower in people with type 2 diabetes than in type 1 diabetes, at baseline (3.4 ± 1.6 vs 7.7 ± 1.3 mU/L, p = 0.042) and during hypoglycaemia (24.7 ± 7.1 vs 62.4 ± 5.8 mU/L, p = 0.001). People with 1 diabetes had lower overall symptom responses than people with type 2 diabetes (45.3 ± 2.7 vs 58.7 ± 6.4, p = 0.018), driven by a lower neuroglycopenic score (27.4 ± 1.8 vs 36.7 ± 4.2, p = 0.012). CONCLUSION: Acute counterregulatory hormone and symptom responses to experimental hypoglycaemia are lower in people with type 1 diabetes than in those with long-standing insulin-treated type 2 diabetes and controls.