Bolusing frequency and amount impacts glucose control during hybrid closed-loop.

AIM: To compare bolus insulin delivery patterns during closed-loop home studies in adults with suboptimally [HbA1c 58-86 mmol/mol (7.5%-10%)] and well-controlled [58 mmol/mol (< 7.5%)] Type 1 diabetes. METHODS: Retrospective analysis of daytime and night-time insulin delivery during home use of closed-loop over 4 weeks. Daytime and night-time controller effort, defined as amount of insulin delivered by closed-loop relative to usual basal insulin delivery, and daytime bolus effort, defined as total bolus insulin delivery relative to total daytime insulin delivery were compared between both cohorts. Correlation analysis was performed between individual bolus behaviour (bolus effort and frequency) and daytime controller efforts, and proportion of time spent within and below sensor glucose target range. RESULTS: Individuals with suboptimally controlled Type 1 diabetes had significantly lower bolus effort (P = 0.038) and daily bolus frequency (P < 0.001) compared with those with well-controlled diabetes. Controller effort during both daytime (P = 0.007) and night-time (P = 0.005) were significantly higher for those with suboptimally controlled Type 1 diabetes. Time when glucose was within the target range (3.9-10.0 mmol/L) during daytime correlated positively with bolus effort (r = 0.37, P = 0.016) and bolus frequency (r = 0.33, P = 0.037). Time when glucose was below the target range during daytime was comparable in both groups (P = 0.36), and did not correlate significantly with bolus effort (r = 0.28, P = 0.066) or bolus frequency (r = -0.21, P = 0.19). CONCLUSION: More frequent bolusing and higher proportion of insulin delivered as bolus during hybrid closed-loop use correlated positively with time glucose was in target range. This emphasises the need for user input and educational support to benefit from this novel therapeutic modality.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, Wellcome Strategic Award (100574/Z/12/Z), EC Horizon 2020 (H2020-SC1-731560), NIDDK (DP3DK112176 and 1UC4DK108520-01), Efficacy and Mechanism Evaluation Programme of National Institute for Health Research (14/23/09) and Helmsley Trust (2016PG-T1D045 and #2016PG-T1D046)

Behavioral Patterns and Associations with Glucose Control During 12-Week Randomized Free-Living Clinical Trial of Day and Night Hybrid Closed-Loop Insulin Delivery in Adults with Type 1 Diabetes

$\textbf{Objectives}$: We evaluated patterns of meal intake, insulin bolus delivery, and fingerstick glucose measurements during hybrid closed-loop and sensor-augmented pump (SAP) therapy, including associations with glucose control. $\textbf{Methods}$: Data were retrospectively analyzed from pump-treated adults with type 1 diabetes who underwent, in random order, 12 weeks free-living closed-loop (n = 32) and 12 weeks SAP (n = 33) periods. We quantified daily patterns of main meals, snacks, prandial insulin boluses, correction boluses, and fingerstick glucose measurements by analyzing data recorded on the study glucometer and on study insulin pump. $\textbf{Results}$: We analyzed 1942 closed-loop days and 2530 SAP days. The total number of insulin boluses was reduced during closed-loop versus SAP periods by mean 1.0 per day (95% confidence interval 0.6–1.4, P < 0.001) mainly because of a reduced number of correction boluses by mean 0.7 per day (0.4–1.0, P < 0.001). Other behavioral patterns were unchanged. The carbohydrate content of snacks but not the number of snacks was positively correlated with (1) glycemic variability as measured by standard deviation of sensor glucose (closed-loop P < 0.05; SAP P < 0.01), (2) mean sensor glucose (P < 0.05), and (3) postintervention HbA1c (P < 0.05). Behavioral patterns explained 47% of between-subject variance in glucose variability during SAP period and 30%–33% of variance of means sensor glucose and postintervention HbA1c. $\textbf{Conclusion}$: Fewer correction boluses are delivered during closed-loop period. The size of snacks appears to worsen glucose control possibly because of carbohydrate-rich content of snacks. Modifiable behavioral patterns may be important determinants of glucose control.We acknowledge support by the staff at the Addenbrooke's Wellcome Trust Clinical Research Facility. 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. Barbara Semlitsch and Markus Schauer (both from Medical University of Graz) supported the study as insulin pump experts. Funding was by Seventh Framework Programme of the European Union (ICT FP7-247138). Additional support for the Artificial Pancreas work was by JDRF, National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome Strategic Award (100574/Z/12/Z), EC Horizon 2020 (H2020-SC1-731560), NIDDK (DP3DK112176 and 1UC4DK108520-01), Efficacy and Mechanism Evaluation Programme of National Institute for Health Research (14/23/09), and Helmsley Trust (Nos. 2016PG-T1D045 and 2016PG-T1D046). Abbott Diabetes Care supplied discounted continuous glucose monitoring devices, sensors, and communication protocol to facilitate real-time connectivity

Manejo de la defoliación y fertilización nitrogenada en pasto llorón, Eragrostis curvula, cv. Tanganyka : 1-rendimiento de materia seca, digestibilidad in vitro y rendimiento de materia seca digestible

p.7-14En una pradera de pasto llorón ubicada en Argerich se estudió el efecto de dos tratamientos de defoliación y tres niveles de fertilización nitrogenada durante tres ciclos consecutivos. El forraje se cortó con una frecuencia de 35 cm de altura o acumulado, hasta el 20 de febrero (primavera-verano), y sus rebrotes otoñales se cortaron en invierno (diferido). En primavera-verano el corte a 35 cm, produjo en promedio más materia seca que el acumulado y en el diferido a la inversa. Sus totales anuales fueron similares. La fertilización aumentó los rendimientos promedios parciales y totales (P menor a 0,05). La digestibiüdad primavera-estival fue mayor con cortes a 35 cm que en el acumulado y ambos tratamientos de defoliación respondieron al nitrógeno pero en sus diferidos el efecto fue de pequeña magnitud. Los rendimientos de materia seca digestible siguieron la misma tendencia que los de materia seca aunque, por influencia primavera-estival, en el total anual el corte a 35 cm superó al acumulado (P menor a 0,05). El rebrote primaveral sólo mostró un efecto residual parcial del fertilizante

Faster insulin action is associated with improved glycaemic outcomes during closed-loop insulin delivery and sensor-augmented pump therapy in adults with type 1 diabetes

We aimed to evaluate the relationship between insulin pharmacodynamics and glycaemic outcomes during closed-loop insulin delivery and sensor-augmented pump therapy. We retrospectively analysed data from a multicentre randomized control trial involving 32 adults with type 1 diabetes receiving day-and-night closed-loop insulin delivery and sensor-augmented pump therapy over 12 weeks. We estimated time-to-peak insulin action (t$_{max,IA}$) and insulin sensitivity (_Ix}) during both interventions, and correlated these with demographic factors and glycaemic outcomes. During both interventions, t$_{max,IA}$ was positively correlated with pre- and post-intervention HbA1c (r = 0.50-0.52, P  < .01) and mean glucose (r = 0.45-0.62, P  < .05), and inversely correlated with time sensor glucose, which was in target range 3.9 to 10 mmol/L (r = -0.64 to -0.47, P  < .05). Increased body mass index was associated with higher t$_{max,I}$ and lower S I (both P  < .05). During closed-loop insulin delivery, t$_{max, IA}$, was positively correlated with glucose variability ( P  < .05). Faster insulin action is associated with improved glycaemic control during closed-loop insulin delivery and sensor-augmented pump therapy.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 Biomed ical 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

Home Use of an Artificial Beta Cell in Type 1 Diabetes.

BACKGROUND: The feasibility, safety, and efficacy of prolonged use of an artificial beta cell (closed-loop insulin-delivery system) in the home setting have not been established. METHODS: In two multicenter, crossover, randomized, controlled studies conducted under free-living home conditions, we compared closed-loop insulin delivery with sensor-augmented pump therapy in 58 patients with type 1 diabetes. The closed-loop system was used day and night by 33 adults and overnight by 25 children and adolescents. Participants used the closed-loop system for a 12-week period and sensor-augmented pump therapy (control) for a similar period. The primary end point was the proportion of time that the glucose level was between 70 mg and 180 mg per deciliter for adults and between 70 mg and 145 mg per deciliter for children and adolescents. RESULTS: Among adults, the proportion of time that the glucose level was in the target range was 11.0 percentage points (95% confidence interval [CI], 8.1 to 13.8) greater with the use of the closed-loop system day and night than with control therapy (P<0.001). The mean glucose level was lower during the closed-loop phase than during the control phase (difference, -11 mg per deciliter; 95% CI, -17 to -6; P<0.001), as were the area under the curve for the period when the glucose level was less than 63 mg per deciliter (39% lower; 95% CI, 24 to 51; P<0.001) and the mean glycated hemoglobin level (difference, -0.3%; 95% CI, -0.5 to -0.1; P=0.002). Among children and adolescents, the proportion of time with the nighttime glucose level in the target range was higher during the closed-loop phase than during the control phase (by 24.7 percentage points; 95% CI, 20.6 to 28.7; P<0.001), and the mean nighttime glucose level was lower (difference, -29 mg per deciliter; 95% CI, -39 to -20; P<0.001). The area under the curve for the period in which the day-and-night glucose levels were less than 63 mg per deciliter was lower by 42% (95% CI, 4 to 65; P=0.03). Three severe hypoglycemic episodes occurred during the closed-loop phase when the closed-loop system was not in use. CONCLUSIONS: Among patients with type 1 diabetes, 12-week use of a closed-loop system, as compared with sensor-augmented pump therapy, improved glucose control, reduced hypoglycemia, and, in adults, resulted in a lower glycated hemoglobin level. (Funded by the JDRF and others; AP@home04 and APCam08 ClinicalTrials.gov numbers, NCT01961622 and NCT01778348.).JDRF (22-2011-668) and Seventh Framework Programme of the European Union (ICT FP7- 247138). Additional support for the Artificial Pancreas work by 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 details of communication protocol to facilitate real-time connectivity. Diasend provided discounted platform for data upload.This is the final version of the article. It was first available from Massachusetts Medical Society via http://dx.doi.org/10.1056/NEJMoa150935

RICHTLINIEN FUR DIE BEWERTUNG VON EINZELLERPROTEIN: BERICHT AUS DER TÄTIGKEIT DER IUPAC COMMISSION ON BIOTECHNOLOGY

Since many years the "Commission on Biotechnology'' of IUPAC is concerned with setting up guidelines for the evaluation of single cell proteins (SCP). In the first general rules for SCP as animal food, mainly hydrocarbons were considered in addition to carbohydrates as starting materials for SCP from yeasts and bacteria. The rules have been published as IUPAC Technical Reports - Number 12 in 1974. The use of methanol as an additional important raw material for SCP demanded an adequate extension of these rules. As a result the "Guidelines for Testing of Single Cell Protein, destined as Protein Source for Animal Feed - II' were published in 1979. In cooperation with the "Commission on Food" of IUPAC and the "Protein Advisory Group" of WHO/FAO, the commission is now preparing once more adapted recommendations for SCP as protein supplements, destined for human consumption

Glossary for Chemists of Terms Used in Biotechnology

The glossary contains definitions and explanatory notes, if needed, of over 230 terms frequently used in publications in the multidisciplinary field of biotechnology. The glossary was developed as a step to help facilitate communication between chemists, chemical engineers, biologists and bioengineers and to make biotechnology and its methodologies more accessible to the chemical profession. The interrelation between chemistry, chemical engineering and the burgeoning areas of molecular biology will be especially important as chemical industrial processes begin to incorporate recombinant DNA techniques, for example. The range of terms includes microbiology, genetic engineering, biochemistry, molecular biology, biochemical engineering, bioprocessing and general concepts of biotechnology

EIN BEITRAG ZUM METHANOL-STOFFWECHSEL UND ZU SEINER REGULATION IN HEFEN

Neben Bakterien wurden in den letzten Jahren auch eine Reihe von Hefen isoliert, die auf Methanol als einziger Kohlenstoff- und Energiequelle wachsen können. Die zentralen biochemischen Probleme bei allen diesen Organismen sind diejenigen der Energieumwandlung, der Biosynthese der Zellbestandteile aus dem C,-Substrat und der Regulation der dazu erforderlichen Reaktionen. Durch die Arbeiten von FUJII und TONOMURA (1) sowie von SAHM und WAGNER (2) konnte gezeigt werden, daß Methanol in Hefen unter Energiegewinn über Formaldehyd und Ameisensäure zu CO, oxidiert werden kann. Dieser dissimilatorische Weg wird von einer Methanol-Oxidase sowie einer Formaldehyd- und einer Formiat-Dehydrogenase katalysiert. Ausgehend von der C,-Oxidationsstufe des Formaldehyds sind nach QUAYLE (3) zwei Stoffwechselwege bekannt, die die Netto-Synthese eines Cz-Korpers aus C,-Verbindungen erlauben. In Abgrenzung zum dissimilatorischen Stoffwechsel werden diese Reaktionswege in dem Begriff "assimilatorischer C,-Stoffwechsel" zusammengefaßt