Basal insulin delivery reduction for exercise in type 1 diabetes: finding the sweet spot

Exercise poses significant challenges to glucose management in type 1 diabetes. In spite of careful planning and manipulation of subcutaneous insulin administration, increased risk of hypoglycaemia and glycaemic variability during and after exercise may occur as a result of inherent delays in insulin action and impaired counter-regulatory hormone responses. Various strategies to mitigate this issue have been advocated in clinical practice, including ingestion of supplementary carbohydrate prior to exercise, reducing background and pre-meal insulin bolus and performing bouts of resistance/high intensity exercise before aerobic exercise. Insulin pump therapy, considered the most physiological form of insulin replacement for type 1 diabetes allows modulation of basal insulin delivery before, during and after exercise. However uncertainty remains regarding the optimal strategy to reduce basal insulin delivery and its efficacy. In this issue of Diabetologia, McAuley and colleagues (DOI: 10.1007/s00125-016-3981-9) report on the impact of a 50% reduction of basal insulin delivery before, during and after moderate-intensity aerobic exercise. Results from this study may contribute to a better understanding of the effects of basal insulin delivery manipulation and may aid in devising therapeutic approaches for glucose management during exercise

Enhancing Representation Learning on High-Dimensional, Small-Size Tabular Data: A Divide and Conquer Method with Ensembled VAEs

Variational Autoencoders and their many variants have displayed impressive ability to perform dimensionality reduction, often achieving state-of-the-art performance. Many current methods however, struggle to learn good representations in High Dimensional, Low Sample Size (HDLSS) tasks, which is an inherently challenging setting. We address this challenge by using an ensemble of lightweight VAEs to learn posteriors over subsets of the feature-space, which get aggregated into a joint posterior in a novel divide-and-conquer approach. Specifically, we present an alternative factorisation of the joint posterior that induces a form of implicit data augmentation that yields greater sample efficiency. Through a series of experiments on eight real-world datasets, we show that our method learns better latent representations in HDLSS settings, which leads to higher accuracy in a downstream classification task. Furthermore, we verify that our approach has a positive effect on disentanglement and achieves a lower estimated Total Correlation on learnt representations. Finally, we show that our approach is robust to partial features at inference, exhibiting little performance degradation even with most features missing

Inpatient hypoglycaemia; should we should we focus on the guidelines, the targets or our tools?

In their thought‐provoking commentary, Levy et al. [1] explore the possible unintended consequences of United Kingdom (UK) guideline targets on the high frequency of hypoglycaemia in people with diabetes who are hospitalized. The authors cite the National Institute for Health and Care Excellence (NICE) and the Joint British Diabetes Societies (JBDS) guidelines pertaining to inpatient, surgical and pregnancy diabetes care. These guidelines suggest using lower limits of glucose targets varying from 4.0 to 6.0 mmol/l [2–4]. Levy et al. propose a lower glucose limit of 5 mmol/l with the catchphrase ‘stop at 5 and keep the inpatient alive’

Evaluation of Energy Properties of Nataw (Xylopia Parviflora), a Lesser Known Species as a Dry Matter Energy Source for Industrial Boilers

According to geography and climatic conditions, Sri Lanka is blessed with several types of renewable energy resources namely biomass, hydro, solar, and wind. Among them, in 2016, biomass is the most common source of energy supply in the country and the largest use of biomass is in the domestic sector for cooking purposes. In Sri Lanka, it has been revealed that nearly 72% of industrial boilers which use biomass as fuel consumes fuel wood, 15% of paddy husk and saw dust, and 13% of coconut shells. Also overall fuel wood demand in industries has been increasing steadily in the recent past. Hence, industrial sector in Sri Lanka use fuel wood as the major source of biomass energy. Current study was conducted with the objective of evaluating fuel wood characteristics of Nataw (Xylopia parviflora) which is a wet zone lesser known species. Selected individuals were categorized in to three Diameter (DBH) classes (i) 5 cm-14.99 cm, (ii) 15 cm- 24.99 cm, (iii) 25 cm-34.99 cm. From each class, 5 individuals were measured and sample wood disk were extracted at 1.3 m height level. Moisture content, density, specific gravity, ash content, volatile matter, fixed carbon, and biomass/ash ratio were measured using standard methods. Certain characteristics including moisture content, density, specific gravity, and ash content showed no significant difference at 0.05 level among three DBH classes. Volatile matter of DBH class (iii) is significantly higher among other DBH classes. Fixed carbon content is significantly lower than other two types of DBH classes. When compared the Xylopia parviflora with Hevea brasiliensis which is a commonly used fuel wood species in biomass boilers in industry, moisture content (31.22%), ash content (1.24%) of Xylopia parviflora is lower than that of Hevea brasiliensis. Even though Calorific values of both species are very close to each other Xylopia parviflora has highest calorific value of 18.92 kJ/g which is 18.74 kJ/g in Hevea brasiliensis. Fuel Value Index (FVI) of Xylopia parviflora is 3055 and while 1122 in Hevea brasiliensis. Study finding concluded that Xylopia parviflora performs better than the Hevea brasiliensis as a fuel wood hence can be a good fuel source for biomass boilers in industries.Keywords: Rubber wood residues, Wood pellets, Energy properties, Mechanical propertie

Hyperglycemia and Death in Cystic Fibrosis–Related Diabetes

OBJECTIVE Diabetes is common in cystic fibrosis and increases the risk of death, yet the role of hyperglycemia remains unproven. An association between glycemia and mortality would provide compelling evidence to support glucose lowering in cystic fibrosis–related diabetes (CFRD). RESEARCH DESIGN AND METHODS Using the U.K. Cystic Fibrosis Registry, we analyzed longitudinal data from 2006 to 2009 in 520 individuals with diabetes. We tested the association between HbA1c and mortality. RESULTS During a median follow-up of 2 years, 36 patients died. The median value of HbA1c was higher in those who died (7.3%) than in those who did not (6.7%). An HbA1c value of ≥6.5% was associated with a threefold increased risk of death (hazard ratio 3.2 [95% CI 1.4–7.3]; P = 0.005) independent of potential confounders. CONCLUSIONS Hyperglycemia trebles the risk of death in patients with CFRD. These findings provide epidemiologic support for continued efforts to improve glycemic control. Diabetes frequently complicates cystic fibrosis. Cystic fibrosis–related diabetes (CFRD) has an incidence in teenagers of up to 6% per year and a prevalence in adults of >30% (1,2). Diabetes further elevates the already high mortality rates in cystic fibrosis (3–5). In individuals without cystic fibrosis, diabetes increases the risk of death, and in individuals with diabetes, hyperglycemia increases the risk of death (6,7). However, no study of CFRD using national data has investigated whether hyperglycemia, per se, increases the risk of death; likewise, no trial has tested whether controlling blood glucose prolongs survival. Proving an association between glycemia and mortality in cystic fibrosis would provide compelling observational evidence to inform clinical practice. Using the U.K. Cystic Fibrosis Registry, we performed longitudinal analyses to test the association between glycemia, as measured by HbA1c, and mortality in individuals with CFRD

Closing the loop overnight at home setting: psychosocial impact for adolescents with type 1 diabetes and their parents.

OBJECTIVE: To explore the experiences of adolescents with type 1 diabetes mellitus (T1DM) and their parents taking part in an overnight closed loop study at home, using qualitative and quantitative research methods. RESEARCH DESIGN AND METHODS: Adolescents aged 12-18 years on insulin pump therapy were recruited to a pilot closed loop study in the home setting. Following training on the use of a study insulin pump and continuous glucose monitoring (CGM), participants were randomized to receive either real-time CGM combined with overnight closed loop or real-time CGM alone followed by the alternative treatment for an additional 21 days with a 2-3-week washout period in between study arms. Semistructured interviews were performed to explore participants' perceptions of the impact of the closed loop technology. At study entry and again at the end of each 21-day crossover arm of the trial, participants completed the Diabetes Technology Questionnaire (DTQ) and Hypoglycemia Fear Survey (HFS; also completed by parents). RESULTS: 15 adolescents and 13 parents were interviewed. Key positive themes included reassurance/peace of mind, confidence, 'time off' from diabetes demands, safety, and improved diabetes control. Key negative themes included difficulties with calibration, alarms, and size of the devices. DTQ results reflected these findings. HFS scores were mixed. CONCLUSIONS: Closed loop insulin delivery represents cutting-edge technology in the treatment of T1DM. Results indicate that the psychological and physical benefits of the closed loop system outweighed the practical challenges reported. Further research from longitudinal studies is required to determine the long-term psychosocial benefit of the closed loop technology

Feasibility of fully automated closed-loop glucose control using continuous subcutaneous glucose measurements in critical illness: a randomized controlled trial.

INTRODUCTION: Closed-loop (CL) systems modulate insulin delivery according to glucose levels without nurse input. In a prospective randomized controlled trial, we evaluated the feasibility of an automated closed-loop approach based on subcutaneous glucose measurements in comparison with a local sliding-scale insulin-therapy protocol. METHODS: Twenty-four critically ill adults (predominantly trauma and neuroscience patients) with hyperglycemia (glucose, ≥10 mM) or already receiving insulin therapy, were randomized to receive either fully automated closed-loop therapy (model predictive control algorithm directing insulin and 20% dextrose infusion based on FreeStyle Navigator continuous subcutaneous glucose values, n = 12) or a local protocol (n = 12) with intravenous sliding-scale insulin, over a 48-hour period. The primary end point was percentage of time when arterial blood glucose was between 6.0 and 8.0 mM. RESULTS: The time when glucose was in the target range was significantly increased during closed-loop therapy (54.3% (44.1 to 72.8) versus 18.5% (0.1 to 39.9), P = 0.001; median (interquartile range)), and so was time in wider targets, 5.6 to 10.0 mM and 4.0 to 10.0 mM (P ≤ 0.002), reflecting a reduced glucose exposure >8 and >10 mM (P ≤ 0.002). Mean glucose was significantly lower during CL (7.8 (7.4 to 8.2) versus 9.1 (8.3 to 13.0] mM; P = 0.001) without hypoglycemia (<4 mM) during either therapy. CONCLUSIONS: Fully automated closed-loop control based on subcutaneous glucose measurements is feasible and may provide efficacious and hypoglycemia-free glucose control in critically ill adults. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01440842

Safety, efficacy and glucose turnover of reduced prandial boluses during closed-loop therapy in adolescents with type 1 diabetes: a randomized clinical trial.

AIMS: To evaluate safety, efficacy and glucose turnover during closed-loop with meal announcement using reduced prandial insulin boluses in adolescents with type 1 diabetes (T1D). METHODS: We conducted a randomized crossover study comparing closed-loop therapy with standard prandial insulin boluses versus closed-loop therapy with prandial boluses reduced by 25%. Eight adolescents with T1D [3 males; mean (standard deviation) age 15.9 (1.5) years, glycated haemoglobin 74 (17) mmol/mol; median (interquartile range) total daily dose 0.9 (0.7, 1.1) IU/kg/day] were studied on two 36-h-long visits. In random order, subjects received closed-loop therapy with either standard or reduced insulin boluses administered with main meals (50-80 g carbohydrates) but not with snacks (15-30 g carbohydrates). Stable-label tracer dilution methodology measured total glucose appearance (Ra_total) and glucose disposal (Rd). RESULTS: The median (interquartile range) time spent in target (3.9-10 mmol/l) was similar between the two interventions [74 (66, 84)% vs 80 (65, 96)%; p = 0.87] as was time spent above 10 mmol/l [21.8 (16.3, 33.5)% vs 18.0 (4.1, 34.2)%; p = 0.87] and below 3.9 mmol/l [0 (0, 1.5)% vs 0 (0, 1.8)%; p = 0.88]. Mean plasma glucose was identical during the two interventions [8.4 (0.9) mmol/l; p = 0.98]. Hypoglycaemia occurred once 1.5 h post-meal during closed-loop therapy with standard bolus. Overall insulin delivery was lower with reduced prandial boluses [61.9 (55.2, 75.0) vs 72.5 (63.6, 80.3) IU; p = 0.01] and resulted in lower mean plasma insulin concentration [186 (171, 260) vs 252 (198, 336) pmol/l; p = 0.002]. Lower plasma insulin was also documented overnight [160 (136, 192) vs 191 (133, 252) pmol/l; p = 0.01, pooled nights]. Ra_total was similar [26.3 (21.9, 28.0) vs 25.4 (21.0, 29.2) µmol/kg/min; p = 0.19] during the two interventions as was Rd [25.8 (21.0, 26.9) vs 25.2 (21.2, 28.8) µmol/kg/min; p = 0.46]. CONCLUSIONS: A 25% reduction in prandial boluses during closed-loop therapy maintains similar glucose control in adolescents with T1D whilst lowering overall plasma insulin levels. It remains unclear whether closed-loop therapy with a 25% reduction in prandial boluses would prevent postprandial hypoglycaemia.US National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK085621). Support for the Artificial Pancreas research programme by the JDRF, Diabetes UK, NIHR Cambridge Biomedical Research Centre, and Wellcome Trust Strategic Award (100574/Z/12/Z) is acknowledged.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/dom.1254