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

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’

Variability of Insulin Requirements Over 12 Weeks of Closed-Loop Insulin Delivery in Adults With Type 1 Diabetes.

OBJECTIVE: To quantify variability of insulin requirements during closed-loop insulin delivery. RESEARCH DESIGN AND METHODS: We retrospectively analyzed overnight, daytime, and total daily insulin amounts delivered during a multicenter closed-loop trial involving 32 adults with type 1 diabetes. Participants applied hybrid day-and-night closed-loop insulin delivery under free-living home conditions over 12 weeks. The coefficient of variation was adopted to measure variability of insulin requirements in individual subjects. RESULTS: Data were analyzed from 1,918 nights, 1,883 daytime periods and 1,564 total days characterized by closed-loop use over 85% of time. Variability of overnight insulin requirements (mean [SD] coefficient of variation 31% [4]) was nearly twice as high as variability of total daily requirements (17% [3], P < 0.001) and was also higher than variability of daytime insulin requirements (22% [4], P < 0.001). CONCLUSIONS: Overnight insulin requirements were significantly more variable than daytime and total daily amounts. This may explain why some people with type 1 diabetes report frustrating variability in morning glycemia.Seventh Framework Programme of the European Union (ICT FP7- 247138). Additional support for the Artificial Pancreas work by JDRF, National Institute for Health Research Cambridge Biomedical Research Centre and Wellcome Strategic Award (100574/Z/12/Z). Abbott Diabetes Care supplied discounted continuous glucose monitoring devices, sensors, and communication protocol to facilitate real-time connectivity. We acknowledge support by the staff at the Addenbrooke’s Wellcome Trust Clinical Research Facility. Jasdip Mangat and John Lum (Jaeb Center) supported development and validation of the closed-loop system. Josephine Hayes (University of Cambridge) provided administrative support. Karen Whitehead (University of Cambridge) provided laboratory support. We acknowledge support by the staff at Profil Institut; Krisztina Schmitz-Grozs provided support as a research physician, Martina Haase supported the study as an insulin pump expert, and Maren Luebkert, Kirstin Kuschma and Elke Przetak provided administrative, coordinating and documentation support.This is the author accepted manuscript. The final version is available from the American Diabetes Association via http://dx.doi.org/10.2337/dc15-262

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

Overnight closed-loop insulin delivery in young people with type 1 diabetes: a free-living, randomized clinical trial.

OBJECTIVE: To evaluate feasibility, safety, and efficacy of overnight closed-loop insulin delivery in free-living youth with type 1 diabetes. RESEARCH DESIGN AND METHODS: Overnight closed loop was evaluated at home by 16 pump-treated adolescents with type 1 diabetes aged 12-18 years. Over a 3-week period, overnight insulin delivery was directed by a closed-loop system, and on another 3-week period sensor-augmented therapy was applied. The order of interventions was random. The primary end point was time when adjusted sensor glucose was between 3.9 and 8.0 mmol/L from 2300 to 0700 h. RESULTS: Closed loop was constantly applied over at least 4 h on 269 nights (80%); sensor data were collected over at least 4 h on 282 control nights (84%). Closed loop increased time spent with glucose in target by a median 15% (interquartile range -9 to 43; P < 0.001). Mean overnight glucose was reduced by a mean 14 (SD 58) mg/dL (P < 0.001). Time when glucose was <70 mg/dL was low in both groups, but nights with glucose <63 mg/dL for at least 20 min were less frequent during closed loop (10 vs. 17%; P = 0.01). Despite lower total daily insulin doses by a median 2.3 (interquartile range -4.7 to 9.3) units (P = 0.009), overall 24-h glucose was reduced by a mean 9 (SD 41) mg/dL (P = 0.006) during closed loop. CONCLUSIONS: Unsupervised home use of overnight closed loop in adolescents with type 1 diabetes is safe and feasible. Glucose control was improved during the day and night with fewer episodes of nocturnal hypoglycemia.Supported by Juvenile Diabetes Research Foundation (#22-2006-1113, #22-2007-1801, #22-2009-801, #22-2009-802), Diabetes UK (BDA07/0003549), National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK085621), Medical Research Council Centre for Obesity and Related metabolic Diseases, and National Institute for Health Research Cambridge Biomedical Research Centre. Abbott Diabetes Care supplied continuous glucose delivery devices and sensors and modified devices to facilitate real-time connectivity.This is the final published version, also available from the American Diabetes Association at http://care.diabetesjournals.org/content/37/5/1204

Day and night home closed-loop insulin delivery in adults with type 1 diabetes: three-center randomized crossover study.

OBJECTIVE: To evaluate the feasibility of day and night closed-loop insulin delivery in adults with type 1 diabetes under free-living conditions. RESEARCH DESIGN AND METHODS: Seventeen adults with type 1 diabetes on insulin pump therapy (means ± SD age 34 ± 9 years, HbA1c 7.6 ± 0.8%, and duration of diabetes 19 ± 9 years) participated in an open-label multinational three-center crossover study. In a random order, participants underwent two 8-day periods (first day at the clinical research facility followed by 7 days at home) of sensor-augmented insulin pump therapy (SAP) or automated closed-loop insulin delivery. The primary end point was the time when sensor glucose was in target range between 3.9 and 10.0 mmol/L during the 7-day home phase. RESULTS: During the home phase, the percentage of time when glucose was in target range was significantly higher during closed-loop compared with SAP (median 75% [interquartile range 61-79] vs. 62% [53-70], P = 0.005). Mean glucose (8.1 vs. 8.8 mmol/L, P = 0.027) and time spent above target (P = 0.013) were lower during closed loop, while time spent below target was comparable (P = 0.339). Increased time in target was observed during both daytime (P = 0.017) and nighttime (P = 0.013). CONCLUSIONS: Compared with SAP, 1 week of closed-loop insulin delivery at home reduces mean glucose and increases time in target without increasing the risk of hypoglycemia in adults with relatively well-controlled type 1 diabetes.This is the author accepted manuscript. The final version can be found published here: http://care.diabetesjournals.org/content/37/7/1931.abstract

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

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

Use of Factory-Calibrated Real-time Continuous Glucose Monitoring Improves Time in Target and HbA1c in a Multiethnic Cohort of Adolescents and Young Adults With Type 1 Diabetes:The MILLENNIALS Study

OBJECTIVEInternational type 1 diabetes registries have shown that HbA1c levels are highest in young people with type 1 diabetes; however, improving their glycemic control remains a challenge. We propose that use of the factory-calibrated Dexcom G6 CGM system would improve glycemic control in this cohort.RESEARCH DESIGN AND METHODSWe conducted a randomized crossover trial in young people with type 1 diabetes (16–24 years old) comparing the Dexcom G6 CGM system and self-monitoring of blood glucose (SMBG). Participants were assigned to the interventions in random order during two 8-week study periods. During SMBG, blinded continuous glucose monitoring (CGM) was worn by each participant for 10 days at the start, week 4, and week 7 of the control period. HbA1c measurements were drawn after enrollment and before and after each treatment period. The primary outcome was time in range 70–180 mg/dL.RESULTSTime in range was significantly higher during CGM compared with control (35.7 ± 13.5% vs. 24.6 ± 9.3%; mean difference 11.1% [95% CI 7.0–15.2]; P < 0.001). CGM use reduced mean sensor glucose (219.7 ± 37.6 mg/dL vs. 251.9 ± 36.3 mg/dL; mean difference −32.2 mg/dL [95% CI −44.5 to −20.0]; P < 0.001) and time above range (61.7 ± 15.1% vs. 73.6 ± 10.4%; mean difference 11.9% [95% CI −16.4 to −7.4]; P < 0.001). HbA1c level was reduced by 0.76% (95% CI −1.1 to −0.4) (−8.5 mmol/mol [95% CI −12.4 to −4.6]; P < 0.001). Times spent below range (<70 mg/dL and <54 mg/dL) were low and comparable during both study periods. Sensor wear was 84% during the CGM period.CONCLUSIONSCGM use in young people with type 1 diabetes improves time in target and HbA1c levels compared with SMBG

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