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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.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\u003EThis article discusses preliminary data from the Islet Transplantation in Type 1 Diabetes study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00434811\u0026amp;atom=%2Fspmdc%2F14%2F19%2F13.atom\u0022\u003ENCT00434811\u003C\/a\u003E]. The Phase 3, open-label, single-group study was conducted by the Clinical Islet Transplantation (CIT) Consortium. The CIT was created by the National Institutes of Health to advance islet transplantation for patients with type 1 diabetes mellitus and severe hypoglycemia and patients who have had a kidney transplant.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EHyperglycemia\/Hypoglycemia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EEndocrinology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Metabolic Syndrome\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHyperglycemia\/Hypoglycemia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EPreliminary data from the Islet Transplantation in Type 1 Diabetes study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00434811\u0026amp;atom=%2Fspmdc%2F14%2F19%2F13.atom\u0022\u003ENCT00434811\u003C\/a\u003E] were presented by Bernhard J. Hering, MD, University of Minnesota, Minneapolis, Minnesota, USA. The Phase 3, open-label, single-group study was conducted by the Clinical Islet Transplantation (CIT) Consortium. The CIT was created by the National Institutes of Health to advance islet transplantation for patients with type 1 diabetes mellitus (T1DM) and severe hypoglycemia (SH) and patients who have had a kidney transplant.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EA total of 8 centers enrolled 48 patients (aged 18 to 65 years) with a diabetes duration of 5 years or longer, an absence of stimulated C-peptide (\u0026lt; .3 ng\/mL), 1 or more episodes of SH in the previous year, and either documented hypoglycemia unawareness or marked glycemic lability. Patients received up to 3 intraportal infusions of purified human pancreatic islets (PHPI) within an 8-month period. Induction immunotherapy included rabbit anti-thymocyte globulin and etanercept, and maintenance immunosuppression consisted of sirolimus and tacrolimus.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EDr. Hering reported secondary efficacy and safety outcomes. The primary outcome\u2014the proportion of patients with an HbA1C less than 7.0% at Day 365 and free of hypoglycemic events from Day 28 to Day 365 inclusive following the first islet transplant\u2014has been submitted for publication. All 48 patients have reached the 1-year follow-up after the initial islet transplant for the primary endpoint evaluation. Of these, 26 received a second transplant and 1 patient received 3 transplants.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe mean dose was 806,587 islet equivalents (IEQs), and the mean number of IEQs per kilogram of body weight was 11,476 in the 48 patients overall. In the patients who received only 1 islet treatment, the mean dose was 589,101 IEQs, and the mean number of IEQs per kilogram of body weight was 8372.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EEvidence of islet graft function was found in approximately 95% of patients at Day 75 and approximately 90% at Day 365, as measured by C-peptide. At Day 365, 50% of patients were insulin-independent (insulin could only be given between Days 75 and 240).\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EInsulin requirements fell from a median at baseline of approximately 0.49 U\/kg\/day to a median of 0.00 U\/kg\/day (range, 0.00 to \u22120.43 U\/kg\/day) at Day 365 and were sustained to Day 730. C-peptide secretion increased in response to a mixed-meal tolerance test to a median 4 ng\/mL at 90 minutes on Day 365, while glucose concentrations decreased to a median of approximately 150 ng\/mL at Day 365. Awareness of hypoglycemia was significantly improved as measured by the Clarke Score (median 6 at baseline reduced to 0 at Day 365; p\u0026lt; .001) and the Ryan Hypoglycemia Score (p\u0026lt; .001). The Glycemic Lability Index decreased from approximately 800 at baseline to approximately 100 at Day 365 (p\u0026lt; .001) and the Mean Amplitude of Glycemic Excursions Score improved (p\u0026lt; .0002). The median percentage of time in glucose range (50 to 180 mg\/dL) was approximately 95% at Day 365.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EThere were no deaths or permanent morbidities related to the study treatment. There were 19 serious adverse events, of which 5 were related to the procedure, 13 to immunosuppression, and 1 to insulin-related hypoglycemia. Other adverse events involved 6 patients with non-zero calculated panel reactive antibodies (only 1 was donor specific) and 1 patient with an acute kidney injury of unknown origin. The initiation of islet therapy transplantation was associated with a small but significant decrease in glomerular filtration rate (\u20138.1 mL\/minute; p\u0026lt; .0001), with no further significant change at Days 75 and 365.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EIn summary, transplanted PHPI safely restored and then sustained glycemic control to near normal levels and provided protection against SH in patients with T1DM.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 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\/14\/19\/13.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?nzp2p2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}