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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\u003ECardiovascular disease (CVD) is the primary cause of morbidity and mortality in people with diabetes, accounting for 70% of all deaths [Lloyd-Jones D et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2009]. Individuals with diabetes experience an enhanced atherosclerotic process, resulting in an increased plaque burden that affects smaller blood vessels, an increased necrotic core within the plaque, and greater macrophage and T-cell infiltration, all of which increase plaque vulnerability to rupture and result in thrombosis [Ross R et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 1999].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ELipid Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ECardiovascular disease (CVD) is the primary cause of morbidity and mortality in people with diabetes, accounting for 70% of all deaths [Lloyd-Jones D et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2009]. Individuals with diabetes experience an enhanced atherosclerotic process, resulting in an increased plaque burden that affects smaller blood vessels, an increased necrotic core within the plaque, and greater macrophage and T-cell infiltration, all of which increase plaque vulnerability to rupture and result in thrombosis [Ross R et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 1999].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EAs in individuals without diabetes, HMG-CoA reductase inhibitors (statins), provide significant primary and secondary protection against vascular events in those with diabetes. Pivotal studies that have documented these benefits include the Heart Protection Study. In patients with diabetes with or without coronary heart disease or other CVD, those who received simvastatin 40 mg daily experienced significant reductions in their relative risk of cardiovascular (CV) events, regardless of their CV history [Collins R et al. \u003Cem\u003ELancet\u003C\/em\u003E 2002].\u003C\/p\u003E\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\/10\/9\/38\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Heart Protection Study Diabetes Subgroups.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-768080450\u0022 data-figure-caption=\u0022Heart Protection Study Diabetes Subgroups.\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\/10\/9\/38\/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\/10\/9\/38\/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\/10\/9\/38\/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\/11573\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-4\u0022 class=\u0022first-child\u0022\u003EHeart Protection Study Diabetes Subgroups.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReprinted from \u003Cem\u003EThe Lancet\u003C\/em\u003E. Volume 360, Issue 9326, The Heart Protection Study Collaborative Group, TMRC\/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo controlled trial, pages 7\u201322, Copyright 2002, with permission from Elsevier.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-5\u0022\u003EIt is also clear that statin therapy is important in primary prevention. The Collaborative AtoRvastatin Diabetes Study (CARDS) demonstrated a 37% relative risk reduction in vascular events among participants who received 10 mg of atorvastatin versus placebo (p=0.001) over 4 years, with significant risk reduction occurring as early as 18 months. It also found a nearly 50% risk reduction in stroke (95% CI, \u221269 to \u221211) [Hitman GA et al. \u003Cem\u003EDiabet Med\u003C\/em\u003E 2007; Colhoun HM et al. \u003Cem\u003EDiabetologia\u003C\/em\u003E 2005; Colhoun HM et al. \u003Cem\u003ELancet\u003C\/em\u003E 2004].\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ENumerous studies also attest to the benefits of extremely low levels of low-density lipoprotein (LDL). In a meta-analysis of trials that involved 27,548 patients with stable CVD or acute coronary syndrome (ACS), Cannon and colleagues identified a 16% odds reduction in coronary death or myocardial infarction among patients who received intensive statin therapy versus moderate therapy (p\u0026lt;0.0001) [Cannon CP et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2006].\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003ESignificant reductions in LDL cholesterol can also result in atherosclerotic regression in patients with diabetes. In A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden (ASTEROID), intensive statin therapy with rosuvastatin 40 mg daily reduced LDL cholesterol from a mean of 130.4 mg\/dL to 60.8 mg\/dL, resulting in significant regression in 3 primary parameters of atherosclerosis (p\u0026lt;0.001) [Nissen SE et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2006].\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EHDL and Triglycerides as Targets in Type 2 Diabetes Mellitus\u003C\/h2\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EWhile the risk of CVD from increased LDL level is significant in patients with diabetes, it is becoming clear that the risk is also related to low levels of high-density lipoprotein (HDL) and high levels of triglycerides (TG), even in individuals with normal LDL. This pattern of mixed dyslipidemia is particularly common among diabetics. Not only does it increase the risk of macrovascular events, it also increases microvascular consequences, such as diabetic neuropathy and retinopathy, neither of which is affected by LDL levels [Assmann G et al. \u003Cem\u003EDiab Vasc Dis Res\u003C\/em\u003E 2010; Assmann G et al. \u003Cem\u003EEur J Clin Invest\u003C\/em\u003E 2007; Fioretto P et al. \u003Cem\u003ENat Rev Endocrinol\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EWhile statins are quite successful in reducing macrovascular events in patients with diabetes, they have little impact on the risk for microvascular events [Fioretto P et al. \u003Cem\u003ENat Rev Endocrinol\u003C\/em\u003E 2010]. In addition, even with their effectiveness in preventing CVD, patients with diabetes still maintain a higher risk of CV events and deaths than those without the disease (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E) [Kearney PM et al. \u003Cem\u003ELancet\u003C\/em\u003E 2008]. Thus, there is a need to address other components of diabetic dyslipidemia.\u003C\/p\u003E\n         \u003Cdiv id=\u0022F2\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\/10\/9\/38\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Risk of CV Events and Deaths in Statin-Treated Patients With or Without Diabetes Mellitus.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-768080450\u0022 data-figure-caption=\u0022Risk of CV Events and Deaths in Statin-Treated Patients With or Without Diabetes Mellitus.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/9\/38\/F2.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\/10\/9\/38\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\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\/10\/9\/38\/F2.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\/11577\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 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-10\u0022 class=\u0022first-child\u0022\u003ERisk of CV Events and Deaths in Statin-Treated Patients With or Without Diabetes Mellitus.\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from A. von Eckardstein, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EUnfortunately, the effect of statins on HDL and TG is also limited [Jones P et al. \u003Cem\u003EAm J Cardiol\u003C\/em\u003E 1998]. Thus, other interventions are required. One option is fenofibrate. However, in the Action to reduce Cardiovascular Risk in Diabetes (ACCORD) trial, patients who were randomized to simvastatin and fenofibrate demonstrated no improvement in CV events compared with those who were randomized to simvastatin and placebo [Ginsberg HN et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010]. A later subgroup analysis found significant benefits in patients with elevated triglycerides (\u0026gt;204 mg\/dL) and extremely low HDL levels (\u226434 mg\/dL) [Ginsberg HN et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010]. This subgroup accounted for 17% of patients in the ACCORD trial. Also, in other fibrate trials, patients with both low HDL cholesterol and elevated triglycerides were found to benefit from treatment with fenofibrate, bezafibrate, or gemfibrozil [Fruchart et al. \u003Cem\u003ECurr Med Res Opin 2010\u003C\/em\u003E]. The message from these findings is that while it may not be appropriate to treat the entire population of patients who have HDL and TG abnormalities with fibrates, it may be appropriate for a subpopulation.\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EEven fibrates are limited in their ability to affect HDL. Currently, there are no approved options for increasing HDL, although the cholesterol-ester transfer protein (CETP) inhibitors that are now in clinical trials offer some potential. Phase II trials of the CETP inhibitor dalcetrapib demonstrated significant reductions in CETP activity compared with placebo in patients with and without type 2 diabetes and\/or metabolic syndrome (p\u0026lt;0.0001 for both) [Devi L et al. \u003Cem\u003EPLoS One\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EAs drugs that target HDL are introduced to clinical practice, it will be important to understand how best to use them. For instance, while lower is better in terms of risk prevention with LDL cholesterol, higher is not necessarily better when it comes to HDL levels, as indicated by a meta-analysis that was published in 2009, revealing a flattening of the benefit beyond current recommended levels [Di Angelantonio E et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2009].\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\/10\/9\/38.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?nzmocp\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?nzmocp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}