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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EClosed-loop systems consist of a continuous glucose sensor that is connected to a computer that contains a glucose control algorithm and this algorithm advises the rate of the insulin pump. This article presents data comparing a bihormonal closed-loop system to control postprandial and post exercise glucose with an open-loop system (usual care, insulin dosing performed by the patient).\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHyperglycemia\/Hypoglycemia\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EClosed-loop systems consist of a continuous glucose sensor that is connected to a computer that contains a glucose control algorithm and this algorithm advises the rate of the insulin pump. Arianne van Bon, MD, Academic Medical Center, Amsterdam, The Netherlands, presented data comparing a bihormonal closed-loop system to control postprandial and post exercise glucose with an open-loop system (usual care, insulin dosing performed by the patient). Overall, the bihormonal closed-loop system (automated glucagon plus insulin delivery) successfully controlled the glucose values in type 1 diabetic patients.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe first prototype, (APPEL 1) was a pilot study that evaluated the feasibility of the bihormonal closed-loop system in 6 subjects with type 1 diabetes postprandially. The closed-loop consisted of subcutaneous continuous glucose monitor (CGM) based on microdialysis, self-learning proportional derivative algorithm built in a personal computer and two D-Tron+ pumps for subcutaneous insulin and glucagon administration [van Bon A et al. \u003Cem\u003EJ Diabetes Sci Techno\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe algorithm had three operating ranges: 1) administer insulin if the glucose level was \u0026gt;7 mmol\/L; 2) add glucagon if the glucose level was \u0026lt;3.2 mmol\/L; 3) issue an eating alert for glucose levels \u0026lt;5 mmol\/L).\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EOne subject was excluded due to technical failure of the CGM. Overall mean venous glucose values were similar between the two systems (open-loop 11.4 mmol\/L [5.2 to 14.7]; closed-loop in 8.7 mmol\/L [7.1 to 8.8]). There was an initial postprandial rise in glucose with the closed-loop system followed by a drop in glucose values to \u0026lt;5mmol\/L. There were four hypoglycemic events (glucose \u0026lt;3.9 mmol\/L) in the closed-loop group compared with one event in the open-loop group. These results showed that the technique was feasible, but adjustments were needed.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EIn the follow-up study (APPEL 2) adjustments were made: a needle type CGM was used instead of microdialysis CGM; two CGMs (one primary and one back up sensor) were used and there was a change in the algorithm. Insulin was administered if glucose levels \u0026gt;6.5 mmol\/L, glucagon was given at glucose levels \u0026lt;6.5 mmol\/L, and eating alerts were issued when glucose levels were \u0026lt;3.5mmol\/L. Rescue glucagon bolus was given when glucose was \u0026lt;4.5 mmol\/L. Also, exercise (30 minutes on a home trainer) was introduced to increase stress on the system. Included were 10 patients (8 men and 2 women, mean age 55.4 years) with type 1 diabetes treated with an insulin pump. Subjects had a mean HbA1C of 8.0%, mean duration of diabetes of 34.6 years, and mean pump use of 11.2 years. The glucose was controlled 2 hours after breakfast, during and one and a half hour post exercise, and four hours after lunch.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EThere were no overall differences in venous and sensor glucose concentrations between the closed-loop system and usual care (open-loop; \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). Significantly higher venous glucose levels (p=0.001) were noted in the closed-loop system post exercise. Significantly higher postprandial breakfast (p=0.001) and significantly lower post exercise (p=0.01) glucose concentrations (AUC) were noted in the closed-loop system. The postprandial lunch glucose control was not different. There were no incidents of severe hypoglycemia. Glucose levels \u0026lt;3.5 mmol\/L were observed in two patients in the open-loop system and four in the closed-loop system. All patients were given glucagon. In conclusion, the closed-loop system was efficient particularly after lunch when all glucose levels were \u0026lt;6.5 mmol\/L suggesting that the glucose level before the meal influences the performance of the algorithm.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/12482\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/12482\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12482\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003EAPPEL 2: Results.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/11\/11\/14.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmxw1\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzmxw1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}