Predicting Blood Glucose with an LSTM and Bi-LSTM Based Deep Neural Network

A deep learning network was used to predict future blood glucose levels, as this can permit diabetes patients to take action before imminent hyperglycaemia and hypoglycaemia. A sequential model with one long-short-term memory (LSTM) layer, one bidirectional LSTM layer and several fully connected layers was used to predict blood glucose levels for different prediction horizons. The method was trained and tested on 26 datasets from 20 real patients. The proposed network outperforms the baseline methods in terms of all evaluation criteria.Comment: 5 pages, submitted to 2018 14th Symposium on Neural Networks and Applications (NEUREL

Closed-loop management of inpatient hyperglycemia.

The prevalence of diabetes in the hospital is increasing and approximately 18-20% of hospital beds are occupied by someone with diabetes [1]. Diabetes disproportionally affects the elderly, with three times greater prevalence in hospitalised people aged over 65 years than in those aged under 45 years [2]. Maintaining near normoglycaemia during hospital admissions can be very challenging. The impact of the current illness, medication changes, alterations to meal timings and intake, and requirement for nutrition support in hospital can all contribute to sub-optimal glucose control. Both hyper- and hypoglycemia in hospital are associated with increased risk of complications, length of stay, admission to the intensive care unit and mortality [3].Diabetes UK (#14/0004878), Swiss National Science Foundation (P1BEP3_165297) and European Foundation for the Study of Diabetes. Additional support for the Artificial Pancreas work by JDRF, National Institute for Health Research Cambridge Biomedical Research Centre and Wellcome Trust Strategic Award (100574/Z/12/Z)

Simplified quantification of insulin, its synthetic analogs and C-peptide in human plasma by means of LC-HRMS.

The quantification of peptide hormones by means of liquid chromatography (LC) coupled to mass spectrometry (MS) or other techniques (e.g. immunoassays) has been a challenging task in modern analytical chemistry. Especially for insulin, its synthetic analogs, and C-peptide, reliable determinations are urgently needed due to their diagnostic value in the management of diabetes and insulin resistance and because of the illicit use of insulin as a performance-enhancing agent in professional sports or as an effective toxin in forensic toxicology. The concomitant measurement of C-peptide and insulin offers an established tool for the diagnostic workup of hypoglycemia (endogenous vs. exogenous hyperinsulinemia), characterizing hepatic insulin clearance, and the assessment of beta-cell function (insulin secretion). Thus, the present approach offers the possibility to determine human insulin and its synthetic analogs (lispro, glulisine, aspart, glargine metabolite, degludec, detemir, porcine, and bovine) and C-peptide simultaneously after sample preparation utilizing protein precipitation and a mixed-mode cation-exchange solid-phase extraction, and subsequent detection by LC-high resolution MS. The method was fully validated regarding the following parameters: specificity, limit of detection (0.2 ng/mL), limit of quantification (0.6 ng/mL), recovery (40-90%), accuracy (78-128%), linearity, precision (< 21%), carry over, robustness, and matrix effects. The proof-of-concept was shown by analyzing authentic plasma samples from adults with class II obesity and prediabetes collected in the course of an oral glucose tolerance test. All sample preparation steps were controlled by two stable isotope-labeled internal standards, namely [[2 H10 ] Leu B6, B11, B15, B17 ]-insulin, and [[13 C6 ] Leu 26, 30 ] C-peptide

Finding the right route for insulin delivery - an overview of implantable pump therapy.

Implantable pump therapy adopting the intraperitoneal route of insulin delivery has been available for the past three decades. The key rationale for implantable pump therapy is the restoration of the portal-peripheral insulin gradient of the normal physiology. Uptake in clinical practice is limited to specialized centers and selected patient populations. Areas covered: Implantable pump therapy is discussed, including technical aspects, rationale for its use, and glycemic and non-glycemic effects. Target populations, summaries of clinical studies and issues related to implantable pump therapy are highlighted. Limitations of implantable pump therapy and its future outlook in clinical practice are presented. Expert opinion: Although intraperitoneal insulin delivery appears closer to the normal physiology, technical, pharmacological, and costs barriers prevent a wider adoption. Evidence from clinical studies remains scarce and inconclusive. As a consequence, the use of implantable pump therapy will be confined to a small population unless considerable technological progress is made and well-conducted studies can demonstrate glycemic and/or non-glycemic benefits justifying wider application.Supported by National Institute of Health Research Cambridge Biomedical Research Centre, Efficacy and Mechanism Evaluation National Institute for Health Research (#14/23/09), The Leona M. & Harry B. Helmsley Charitable Trust (#2016PG-T1D045), JDRF (#2-SRA-2014-256-M-R), National Institute of Diabetes and Digestive and Kidney Diseases (1UC4DK108520-01), and Diabetes UK (#14/0004878). LB receives support from the Swiss National Science Foundation (P1BEP3_165297)

Closed-loop for type 1 diabetes – an introduction and appraisal for the generalist

BACKGROUND: Rapid progress over the past decade has been made with the development of the 'Artificial Pancreas', also known as the closed-loop system, which emulates the feedback glucose-responsive functionality of the pancreatic beta cell. The recent FDA approval of the first hybrid closed-loop system makes the Artificial Pancreas a realistic therapeutic option for people with type 1 diabetes. In anticipation of its advent into clinical care, we provide a primer and appraisal of this novel therapeutic approach in type 1 diabetes for healthcare professionals and non-specialists in the field. DISCUSSION: Randomised clinical studies in outpatient and home settings have shown improved glycaemic outcomes, reduced risk of hypoglycaemia and positive user attitudes. User input and interaction with existing closed-loop systems, however, are still required. Therefore, management of user expectations, as well as training and support by healthcare providers are key to ensure optimal uptake, satisfaction and acceptance of the technology. An overview of closed-loop technology and its clinical implications are discussed, complemented by our extensive hands-on experience with closed-loop system use during free daily living. CONCLUSIONS: The introduction of the artificial pancreas into clinical practice represents a milestone towards the goal of improving the care of people with type 1 diabetes. There remains a need to understand the impact of user interaction with the technology, and its implication on current diabetes management and care

Available at a flash: a new way to check glucose.

Type 1 diabetes accounts for 5–10% of diabetes cases diagnosed worldwide.1 Hypoglycaemia is common and can limit efforts to tighten glucose control, lower quality of life,2 and increase mortality.3 Insulin analogues, structured education, insulin pump therapy, and continuous glucose monitoring have helped to decrease the burden of hypoglycaemia,4, 5 but it remains considerable.National Institute of Diabetes and Digestive and Kidney Diseases, JDRF, Diabetes UK, Helmsley Trust, National Institute for Health Research, Cambridge Biomedical Research Centre, Wellcome Trust (Strategic Award

Effectiveness of Dietary Interventions in the Treatment of Endometriosis: a Systematic Review

A patients’ increasing interest in dietary modifications as a possible complementary or alternative treatment of endometriosis is observed. Unfortunately, the therapeutic potential of dietary interventions is unclear and to date no guidelines to assist physicians on this topic exist. The aim of this study, therefore, was to systematically review the existing studies on the effect of dietary interventions on endometriosis. An electronic-based search was performed in MEDLINE and COCHRANE. We included human and animal studies that evaluated a dietary intervention on endometriosis-associated symptoms or other health outcomes. Studies were identified and coded using standard criteria, and the risk of bias was assessed with established tools relevant to the study design. We identified nine human and 12 animal studies. Out of the nine human studies, two were randomized controlled trials, two controlled studies, four uncontrolled before-after studies, and one qualitative study. All of them assessed a different dietary intervention, which could be classified in one of the following principle models: supplementation with selected dietary components, exclusion of selected dietary components, and complete diet modification. Most of the studies reported a positive effect on endometriosis; they were however characterized by moderate or high-risk bias possibly due to the challenges of conducting dietary intervention trials. According to the available level of evidence, we suggest an evidence-based clinical approach for physicians to use during consultations with their patients. Further well-designed randomized controlled trials are needed to accurately determine the short-term and long-term effectiveness and safety of different dietary interventions

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

Characteristics of inflammatory response and repair after experimental blast lung injury in rats.

BACKGROUND AND OBJECTIVES Blast-induced lung injury is associated with inflammatory, which are characterised by disruption of the alveolar-capillary barrier, haemorrhage, pulmonary infiltrateration causing oedema formation, pro-inflammatory cytokine and chemokine release, and anti-inflammatory counter-regulation. The objective of the current study was to define sequence of such alterations in with establishing blast-induced lung injury in rats using an advanced blast generator. METHODS Rats underwent a standardized blast wave trauma and were euthanised at defined time points. Non-traumatised animals served as sham controls. Obtained samples from bronchoalveolar lavage fluid (BALF) at each time-point were assessed for histology, leukocyte infiltration and cytokine/chemokine profile. RESULTS After blast lung injury, significant haemorrhage and neutrophil infiltration were observed. Similarly, protein accumulation, lactate dehydrogenase activity (LDH), alveolar eicosanoid release, matrix metalloproteinase (MMP)-2 and -9, pro-Inflammatory cytokines, including tumour necrosis factor (TNF) and interleukin (IL) -6 raised up. While declining in the level of anti-inflammatory cytokine IL-10 occurred. Ultimately, pulmonary oedema developed that increased to its maximum level within the first 1.5 h, then recovered within 24 h. CONCLUSION Using a stablished model, can facilitate the study of inflammatory response to blast lung injury. Following the blast injury, alteration in cytokine/chemokine profile and activity of cells in the alveolar space occurs, which eventuates in alveolar epithelial barrier dysfunction and oedema formation. Most of these parameters exhibit time-dependent return to their basal status that is an indication to resilience of lungs to blast-induced lung injury