Insulin therapy and dietary adjustments to normalize glycaemia and prevent nocturnal hypoglycaemia after evening exercise in type 1 diabetes: a randomized controlled trial

Introduction Evening-time exercise is a frequent cause of severe hypoglycemia in type 1 diabetes, fear of which deters participation in regular exercise. Recommendations for normalizing glycemia around exercise consist of prandial adjustments to bolus insulin therapy and food composition, but this carries only short-lasting protection from hypoglycemia. Therefore, this study aimed to examine the impact of a combined basal-bolus insulin dose reduction and carbohydrate feeding strategy on glycemia and metabolic parameters following evening exercise in type 1 diabetes. Methods Ten male participants (glycated hemoglobin: 52.4±2.2 mmol/mol), treated with multiple daily injections, completed two randomized study-days, whereby administration of total daily basal insulin dose was unchanged (100%), or reduced by 20% (80%). Participants attended the laboratory at ∼08:00 h for a fasted blood sample, before returning in the evening. On arrival (∼17:00 h), participants consumed a carbohydrate meal and administered a 75% reduced rapid-acting insulin dose and 60 min later performed 45 min of treadmill running. At 60 min postexercise, participants consumed a low glycemic index (LGI) meal and administered a 50% reduced rapid-acting insulin dose, before returning home. At ∼23:00 h, participants consumed a LGI bedtime snack and returned to the laboratory the following morning (∼08:00 h) for a fasted blood sample. Venous blood samples were analyzed for glucose, glucoregulatory hormones, non-esterified fatty acids, β-hydroxybutyrate, interleukin 6, and tumor necrosis factor α. Interstitial glucose was monitored for 24 h pre-exercise and postexercise. Results Glycemia was similar until 6 h postexercise, with no hypoglycemic episodes. Beyond 6 h glucose levels fell during 100%, and nine participants experienced nocturnal hypoglycemia. Conversely, all participants during 80% were protected from nocturnal hypoglycemia, and remained protected for 24 h postexercise. All metabolic parameters were similar. Conclusions Reducing basal insulin dose with reduced prandial bolus insulin and LGI carbohydrate feeding provides protection from hypoglycemia during and for 24 h following evening exercise. This strategy is not associated with hyperglycemia, or adverse metabolic disturbances

Gut microbiota of Type 1 diabetes patients with good glycaemic control and high physical fitness is similar to people without diabetes: an observational study

Type 1 diabetes is the product of a complex interplay between genetic susceptibility and exposure to environmental factors. Existing bacterial profiling studies focus on people who are most at risk at the time of diagnosis; there are limited data on the gut microbiota of people with long-standing Type 1 diabetes. This study compared the gut microbiota of patients with Type 1 diabetes and good glycaemic control and high levels of physical-fitness with that of matched controls without diabetes.Ten males with Type 1 diabetes and ten matched controls without diabetes were recruited; groups were matched for gender, age, BMI, peak oxygen uptake (VO2max ), and exercise habits. Stool samples were analysed using next-generation sequencing of the 16S rRNA gene to obtain bacterial profiles from each individual. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was implemented to predict the functional content of the bacterial operational taxonomic units.Faecalibacterium sp., Roseburia sp. and Bacteroides sp. were typically the most abundant members of the community in both patients with Type 1 diabetes and controls, and were present in every sample in the cohort. Each bacterial profile was relatively individual and no significant difference was reported between the bacterial profiles or the Shannon diversity indices of Type 1 diabetes compared with controls. The functional profiles were more conserved and the Type 1 diabetes group were comparable with the control group.We show that both gut microbiota and resulting functional bacterial profiles from patients with long-standing Type 1 diabetes in good glycaemic control and high physical fitness levels are comparable with those of matched people without diabetes. This article is protected by copyright. All rights reserved

Expiratory model-based method to monitor ARDS disease state

INTRODUCTION: Model-based methods can be used to characterise patient-specific condition and response to mechanical ventilation (MV) during treatment for acute respiratory distress syndrome (ARDS). Conventional metrics of respiratory mechanics are based on inspiration only, neglecting data from the expiration cycle. However, it is hypothesised that expiratory data can be used to determine an alternative metric, offering another means to track patient condition and guide positive end expiratory pressure (PEEP) selection. METHODS: Three fully sedated, oleic acid induced ARDS piglets underwent three experimental phases. Phase 1 was a healthy state recruitment manoeuvre. Phase 2 was a progression from a healthy state to an oleic acid induced ARDS state. Phase 3 was an ARDS state recruitment manoeuvre. The expiratory time-constant model parameter was determined for every breathing cycle for each subject. Trends were compared to estimates of lung elastance determined by means of an end-inspiratory pause method and an integral-based method. All experimental procedures, protocols and the use of data in this study were reviewed and approved by the Ethics Committee of the University of Liege Medical Faculty. RESULTS: The overall median absolute percentage fitting error for the expiratory time-constant model across all three phases was less than 10 %; for each subject, indicating the capability of the model to capture the mechanics of breathing during expiration. Provided the respiratory resistance was constant, the model was able to adequately identify trends and fundamental changes in respiratory mechanics. CONCLUSION: Overall, this is a proof of concept study that shows the potential of continuous monitoring of respiratory mechanics in clinical practice. Respiratory system mechanics vary with disease state development and in response to MV settings. Therefore, titrating PEEP to minimal elastance theoretically results in optimal PEEP selection. Trends matched clinical expectation demonstrating robustness and potential for guiding MV therapy. However, further research is required to confirm the use of such real-time methods in actual ARDS patients, both sedated and spontaneously breathing.Peer reviewe

The inflammation, vascular repair and injury responses to exercise in fit males with and without Type 1 diabetes: an observational study.

Type 1 diabetes is associated with raised inflammation, impaired endothelial progenitor cell mobilisation and increased markers of vascular injury. Both acute and chronic exercise is known to influence these markers in non-diabetic controls, but limited data exists in Type 1 diabetes. We assessed inflammation, vascular repair and injury at rest and after exercise in physically-fit males with and without Type 1 diabetes.Ten well-controlled type 1 diabetes (27 ± 2 years; BMI 24 ± 0.7 kg.m(2); HbA1c 53.3 ± 2.4 mmol/mol) and nine non-diabetic control males (27 ± 1 years; BMI 23 ± 0.8 kg.m(2)) matched for age, BMI and fitness completed 45-min of running. Venous blood samples were collected 60-min before and 60-min after exercise, and again on the following morning. Blood samples were processed for TNF-α using ELISA, and circulating endothelial progenitor cells (cEPCs; CD45(dim)CD34(+)VEGFR2(+)) and endothelial cells (cECs; CD45(dim)CD133(-)CD34(+)CD144(+)) counts using flow-cytometry.TNF-α concentrations were 4-fold higher at all-time points in Type 1 diabetes, when compared with control (P 0.05). Within the Type 1 diabetes group, the delta change in cEPCS from rest to the following morning was related to HbA1c (r = -0.65, P = 0.021) and TNF-α (r = -0.766, P = 0.005).Resting cEPCs and cECs in Type 1 diabetes patients with excellent HbA1c and high physical-fitness are comparable to healthy controls, despite eliciting 4-fold greater TNF-α. Furthermore, Type 1 diabetes patients appear to have a blunted post-exercise cEPCs response (vascular repair), whilst a biomarker of vascular injury (cECs) remained comparable to healthy controls

A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve.

AimsThe mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocardial perfusion reserve index, and diastolic filling.Materials and resultsRandomized, double-blind, placebo-controlled, crossover, mechanistic trial in subjects with evidence of CMD [invasive coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI)]. Short-term oral ranolazine 500-1000 mg twice daily for 2 weeks vs. placebo. Angina measured by Seattle Angina Questionnaire (SAQ) and SAQ-7 (co-primaries), diary angina (secondary), stress MPRI, diastolic filling, quality of life (QoL). Of 128 (96% women) subjects, no treatment differences in the outcomes were observed. Peak heart rate was lower during pharmacological stress during ranolazine (-3.55 b.p.m., P < 0.001). The change in SAQ-7 directly correlated with the change in MPRI (correlation 0.25, P = 0.005). The change in MPRI predicted the change in SAQ QoL, adjusted for body mass index (BMI), prior myocardial infarction, and site (P = 0.0032). Low coronary flow reserve (CFR <2.5) subjects improved MPRI (P < 0.0137), SAQ angina frequency (P = 0.027), and SAQ-7 (P = 0.041).ConclusionsIn this mechanistic trial among symptomatic subjects, no obstructive CAD, short-term late sodium current inhibition was not generally effective for SAQ angina. Angina and myocardial perfusion reserve changes were related, supporting the notion that strategies to improve ischaemia should be tested in these subjects.Trial registrationclinicaltrials.gov Identifier: NCT01342029

Organizations and efficiency in public services: The case of English lighthouses revisited

Abstract: Foundational debates about public service provision originate with the study of private lighthouses in England and Wales. We provide a new empirical assessment of cost and technical efficiency of competing lighthouse organizations in the early 1800s. Those with more private control charged ships higher fees and had greater operating costs. Lights with more local representation and funding provided lights of more local use and were most cheaply maintained. Our results help explain why government promoted nonprofit organizations to run lighthouses over private operators. We provide new insights into the role of private enterprise and nonprofit organizations in public service provision

Surface Characterisation Based Tool Wear Monitoring in Peripheral milling

The progress of surface metrology in the last decade has led to improved 3D characterisation of surfaces which offers the possibility of monitoring manufacturing operations to give highly detailed information regarding the machine tool condition. This paper presents a case study where areal surface characterisation is used to monitor tool wear in peripheral milling. Due to the fact that tool wear has a direct effect on the machined workpiece surface, the machined surface topography contains much information concerning the machining conditions including the tool wear state. Through analysing the often subtle changes in the surface topography the tool wear state can be highlighted. This paper utilises areal surface characterization, areal auto-correlation function (AACF) and pattern analysis to illustrate the effect of tool wear on the workpiece surface. The result shows that: (1) tool wear, previously difficult to detect will influence almost all of the areal surface parameters; (2) the pattern features of AACF spectrum can reflect the subtle surface texture variation with increasing tool wear. The authors consider that, combined analysis of the surface roughness and its AACF spectrum are a good choice for monitoring the tool wear state especially with the latest developments in on-machine surface metrology