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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\u003EPreviously published results from the Action to Control Cardiovascular Risk in Diabetes study [ACCORD; ACCORD Study Group. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2008] showed an increased risk of all-cause and cardiovascular (CV) mortality in the intensive control group (HbA1C target, \u0026lt;6.0%) compared with the less intensive group (HbA1C target, 7.0% to 7.9%). Several post hoc analyses did not find a conclusive link between the ACCORD results and factors such as hypoglycemia, low HbA1C, the rapid decline in HbA1C during the first year of the study, weight gain, and specific medication use.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInsulin\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHypertensive Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHyperglycemia\/Hypoglycemia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELipid Disorders Diabetes Mellitus\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInsulin\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHypertensive Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHyperglycemia\/Hypoglycemia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELipid Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EEndocrinology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Metabolic Syndrome\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EPreviously published results from the Action to Control Cardiovascular Risk in Diabetes study [ACCORD; ACCORD Study Group. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2008] showed an increased risk of all-cause and cardiovascular (CV) mortality in the intensive control group (HbA1C target, \u0026lt;6.0%) compared with the less intensive group (HbA1C target, 7.0% to 7.9%). \u201cThis brought a huge puzzle to the diabetes community, to figure out why we were seeing this result,\u201d said Elias S. Siraj, MD, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. Several post hoc analyses have been conducted to date to determine what factors may have influenced this outcome [ACCORD Study Group. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2008; Bonds DE et al. \u003Cem\u003EBMJ\u003C\/em\u003E 2010; Riddle MC et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2010; Seaquist ER et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2012]. These analyses did not find a conclusive link between the ACCORD results and factors such as hypoglycemia, low HbA1C, the rapid decline in HbA1C during the first year of the study, weight gain, and specific medication use.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ETo better understand the findings of this study, ACCORD investigators hypothesized that higher doses of exogenous insulin may be associated with the CV mortality results from the ACCORD trial. To investigate this idea, data for insulin exposure and CV mortality from 10,163 patients were analyzed. HRs and 95% CIs were calculated, and multivariable Cox regression performed to choose the most appropriate baseline covariates and models.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe updated average total, basal, and bolus insulin doses were significantly higher in the intensive-control arm (all p\u0026lt;0.0001). In addition, there was a significant linear association between the updated average HbA1C level and updated average insulin dose in both groups (both p\u0026lt;0.0001). Four different Cox proportional hazards models were employed to determine HRs for CV mortality. The first model controlled for the following 14 baseline covariates: age, history of CV disease, heart failure, QT-index, baseline HbA1C value, high-density lipoprotein, amputation, presence of peripheral neuropathy, serum creatinine, urinary ratio of albumin to creatinine, use of angiotensin receptor blockers, educational status, presence of integrated health plan, and presence of certified diabetes educator on staff at randomization. Model 2 added assignment to blood pressure or lipid trial, treatment assignment within these, severe hypoglycemia, and weight change. Model 3 added the updated average HbA1C, and Model 4 added the glycemic treatment arm assignment. Results from all 4 models by total, basal, and bolus insulin are presented in \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E.\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\/13886\/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\/13886\/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\/13886\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-5\u0022 class=\u0022first-child\u0022\u003EHRs for CV Mortality of Insulin Dose (per 1 unit\/kg) From Cox Proportional Hazards Model\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-7\u0022\u003EBased on the unadjusted HRs, a daily insulin dose increase by 1 unit\/kg of body weight was associated with a 1.83- (total insulin), 2.29- (basal insulin) and 3.36-fold increase in risk of CV mortality (all p\u0026lt;0.0001). However, results from the four models did not confirm these findings. After adjustment for baseline covariates in Model 1, the HRs became nonsignificant indicating no association of insulin dose with CV mortality. Additionally, no association between insulin dose and CV mortality emerged after adjustments were made for on-treatment factors.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EDr. Siraj concluded that these results do not support the idea that insulin dose is an independent risk factor for CV mortality in the ACCORD population.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 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\/13\/11\/12.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?nznqs2\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?nznqs2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}