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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\u003EDiabetes mellitus (DM) adds a layer of complexity to cardiovascular disease (CVD), and mortality rates among individuals with DM are 2- to 3-fold higher compared with those without DM [Preis SR. \u003Cem\u003ECirculation\u003C\/em\u003E 2009]. This article discusses the challenges and treatment strategies that are associated with DM and CVD.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ecardiometabolic disorder\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecoronary artery disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ediabetes mellitus\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EDiabetes mellitus (DM) adds a layer of complexity to cardiovascular disease (CVD), and mortality rates among individuals with DM are 2- to 3-fold higher compared with those without DM [Preis SR. \u003Cem\u003ECirculation\u003C\/em\u003E 2009]. Richard Nesto, MD, FACC, Lahey Clinic Medical Center, Burlington, MA, discussed the challenges and treatment strategies that are associated with DM and CVD.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003ERecent studies have investigated the effect of stringent glucose regulation on CVD risk in patients with type 2 DM. In the Action to Control CardiOvascular Risk in Diabetes (ACCORD) study, 10,251 patients with a median glycated hemoglobin A1c (HbA1c) level of 8.1% were randomized to receive either intensive (target HbA1c \u0026lt;6.0%) or standard (target HbA1c 7.0% to 7.9%) therapy. The primary outcome was a composite of nonfatal myocardial infarction (MI), nonfatal stroke, or death from cardiovascular (CV) causes (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). Intensive therapy was discontinued after a mean follow-up of 3.5 years due to increased rates of mortality in this group (HR, 1.22; 95% CI, 1.01 to 1.46; p=0.04). Dr. Nesto pointed out that the excess risk of death that was associated with intensive treatment occurred in patients who demonstrated no HbA1c reduction from baseline in the first year and\/or had an average HbA1c level of \u0026gt;7.0%. Hypoglycemia was also more frequent in the intensive therapy group (p\u0026lt;0.001); however, there was no evidence that it contributed to increased mortality [ACCORD Study Group. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2008].\u003C\/p\u003E\n         \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\/11551\/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\/11551\/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\/11551\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-4\u0022 class=\u0022first-child\u0022\u003EACCORD Primary and Secondary Outcomes.\u003Csup\u003E*\u003C\/sup\u003E\n               \u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EFindings from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study demonstrated that intensive glucose control (use of modified release gliclazide plus other drugs to achieve HbA1c levels \u22646.5%) reduced the incidence of combined major macrovascular and microvascular events, as well as microvascular events alone, compared with standard therapy at 5 years (p=0.01 for both), primarily owing to a 21% reduction in relative risk of nephropathy (HR, 0.79; 95% CI, 0.66 to 0.93; p=0.006) [The ADVANCE Collaborative Group. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2008]. Findings from the United Kingdom Prospective Diabetes Study (UKPDS), a prospective study of intensive glucose lowering in patients with type 2 DM, further support the microvascular benefit of intensive glucose control. In UKPDS, patients with type 2 DM were randomized to either conventional therapy (dietary restriction) or intensive therapy (either sulfonylurea or insulin, or metformin in overweight patients). Subjects who received intensive glucose therapy had a lower risk of microvascular complications compared with those who received conventional therapy [Holman RR. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2008]. A 10-year follow-up revealed continued reductions in the relative risk of microvascular disease (24%; p=0.001) as well as risk reductions for MI (15%; p=0.01) and death from any cause (13%; p=0.007) in the sulfonylurea\/insulin group, which emerged over time as more events occurred. Significant reductions in the relative risk of MI (33%; p=0.005), any diabetes-related endpoint (21%; p=0.01), and death from any cause (27%; p=0.002) were noted in the metformin group compared with standard therapy at the 10-year post-trial follow-up.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003ERobert L. Frye, MD, Mayo Clinic, Rochester, MN, discussed the Bypass Angioplasty Revascularization 2 Diabetes (BARI-2D) study, which evaluated treatment options for coronary artery disease (CAD) and glycemic control in patients with type 2 DM. Dr. Frye emphasized that BARI-2D is a comparison of management strategies for myocardial ischemia and glycemic control rather than a test of individual diabetes drugs, different HbA1c targets, or percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). In BARI-2D, 2368 patients with type 2 DM (mean duration of 10.4 years and mean HbA1c=7.7%) and documented myocardial ischemia (\u22651 significant coronary stenosis at angiography) were randomized as part of a 2-by-2 factorial design to receive either prompt revascularization (PCI or CABG, as determined by the local cardiologist) with intensive medical therapy or intensive medical therapy alone and subsequently randomized to either insulin sensitization (IS) or insulin provision (IP) therapy. The primary endpoints were the rate of death and a composite of death, MI, or stroke (major CV events).\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EOverall, CV events and mortality were similar for prompt revascularization versus delayed or no revascularization (p=0.70 for CV events and p=0.97 for survival), as well as for IS versus IP (p=0.13 for CV events and p=0.89 for survival) at 5 years. However, among patients who were selected for the CABG stratum, revascularization was associated with a lower rate of major CV events compared with medical therapy (p=0.01), particularly among those who received IS (p=0.002; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Additionally, IS therapy was associated with less weight gain (0.3 vs 2.1 kg), decreased waist circumference (\u22120.1\u00b19.1 cm vs +1.9\u00b18.4), and fewer hypoglycemic events (5.9% vs 9.2%; p=0.003) compared with IP therapy [The BARI-2D Study Group. \u003Cem\u003ENew Engl J Med\u003C\/em\u003E 2009; Rutter MK \u0026amp; Nesto RW. \u003Cem\u003EDiab Vasc Dis Res\u003C\/em\u003E 2010]. Dr. Frye concluded that for patients who are similar to those in BARI 2D with extensive multivessel disease, CABG has an advantage in reducing event rates compared with initial medical therapy alone. In applying these results in clinical practice, comorbidities, age, and other factors must also be considered. The role of insulin sensitization merits further investigation, based on the BARI-2D results, added Dr. Frye.\u003C\/p\u003E\n         \u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/6\/8\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022BARI-2D: Rates of Survival and Freedom from Major CV Events, According to PCI and CABG Strata.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1385544392\u0022 data-figure-caption=\u0022BARI-2D: Rates of Survival and Freedom from Major CV Events, According to PCI and CABG Strata.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/6\/8\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/6\/8\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/6\/8\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11546\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\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-9\u0022 class=\u0022first-child\u0022\u003EBARI-2D: Rates of Survival and Freedom from Major CV Events, According to PCI and CABG Strata.\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003ECopyright \u00a9 2009 Massachusetts Medical Society. All rights reserved.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EMetabolic Syndrome (MetS) also plays a role in CVD risk and may predict diabetes independently of other factors [Lorenzo C. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2003]; therefore, \u201cdiabeteslike\u201d strategies for prevention are merited, noted Dr. Nesto. MetS components include obesity, increased waist circumference, fasting glucose \u0026gt;100 mg\/dL, high triglyceride\/HDL ratio, microalbuminuria, and C-reactive protein \u0026gt;3.0. MetS has been associated with lipid-rich plaques, which may contribute to increased risk of plaque vulnerability [Amano T. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2007]. There is also a strong association between abnormal glucose metabolism, a characteristic of MetS, and mortality, and there may be indications of MetS and CVD risk early in life [Barr EL. \u003Cem\u003ECirculation\u003C\/em\u003E 2007; Caballero AE. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2008; Atabek ME. \u003Cem\u003EPediatrRed\u003C\/em\u003E 2007; Urbina Em. \u003Cem\u003ECirculation\u003C\/em\u003E 2009]. Delivering optimal \u201cglobal\u201d treatment is a responsibility that must be shared by all health care providers, concluded Dr. Nesto.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2010 MD Conference Express\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\/9\/6\/8.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_figures.js?nzmuu2\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_openurl.js?nzmuu2\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?nzmuu2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}