{"markup":"\u003C?xml version=\u00221.0\u0022 encoding=\u0022UTF-8\u0022 ?\u003E\n    \u003Chtml version=\u0022HTML+RDFa+MathML 1.1\u0022\n    xmlns:content=\u0022http:\/\/purl.org\/rss\/1.0\/modules\/content\/\u0022\n    xmlns:dc=\u0022http:\/\/purl.org\/dc\/terms\/\u0022\n    xmlns:foaf=\u0022http:\/\/xmlns.com\/foaf\/0.1\/\u0022\n    xmlns:og=\u0022http:\/\/ogp.me\/ns#\u0022\n    xmlns:rdfs=\u0022http:\/\/www.w3.org\/2000\/01\/rdf-schema#\u0022\n    xmlns:sioc=\u0022http:\/\/rdfs.org\/sioc\/ns#\u0022\n    xmlns:sioct=\u0022http:\/\/rdfs.org\/sioc\/types#\u0022\n    xmlns:skos=\u0022http:\/\/www.w3.org\/2004\/02\/skos\/core#\u0022\n    xmlns:xsd=\u0022http:\/\/www.w3.org\/2001\/XMLSchema#\u0022\n    xmlns:mml=\u0022http:\/\/www.w3.org\/1998\/Math\/MathML\u0022\u003E\n  \u003Chead\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_itu2PgFdrjV-docKmLK8Jn5oXe_05RgvQh73eOhI_mE.js\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_at_symbol.js?nzln31\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_article_reference_popup.js?nzln31\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_I8yX6RYPZb7AtMcDUA3QKDZqVkvEn35ED11_1i7vVpc.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\n(function(i,s,o,g,r,a,m){i[\u0022GoogleAnalyticsObject\u0022]=r;i[r]=i[r]||function(){(i[r].q=i[r].q||[]).push(arguments)},i[r].l=1*new Date();a=s.createElement(o),m=s.getElementsByTagName(o)[0];a.async=1;a.src=g;m.parentNode.insertBefore(a,m)})(window,document,\u0022script\u0022,\u0022\/\/www.google-analytics.com\/analytics.js\u0022,\u0022ga\u0022);ga(\u0022create\u0022, \u0022UA-15605596-27\u0022, {\u0022cookieDomain\u0022:\u0022auto\u0022});ga(\u0022set\u0022, \u0022page\u0022, location.pathname + location.search + location.hash);ga(\u0022send\u0022, \u0022pageview\u0022);ga(\u0027create\u0027, \u0027UA-189672-26\u0027, \u0027auto\u0027, {\u0027name\u0027: \u0027hwTracker\u0027});\r\nga(\u0027hwTracker.send\u0027, \u0027pageview\u0027);\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\njQuery.extend(Drupal.settings, {\u0022basePath\u0022:\u0022\\\/\u0022,\u0022pathPrefix\u0022:\u0022\u0022,\u0022highwire\u0022:{\u0022markup\u0022:[{\u0022requested\u0022:\u0022full-text\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;15\\\/4\\\/23\u0022},{\u0022requested\u0022:\u0022long\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;15\\\/4\\\/23\u0022}],\u0022ac\u0022:{\u0022spmdc;15\\\/4\\\/23\u0022:{\u0022access\u0022:{\u0022reprint\u0022:true,\u0022full\u0022:true},\u0022pisa_id\u0022:\u0022spmdc;15\\\/4\\\/23\u0022,\u0022atom_uri\u0022:\u0022\u0022,\u0022jcode\u0022:\u0022spmdc\u0022}}},\u0022googleanalytics\u0022:{\u0022trackOutbound\u0022:1,\u0022trackMailto\u0022:1,\u0022trackDownload\u0022:1,\u0022trackDownloadExtensions\u0022:\u00227z|aac|arc|arj|asf|asx|avi|bin|csv|doc(x|m)?|dot(x|m)?|exe|flv|gif|gz|gzip|hqx|jar|jpe?g|js|mp(2|3|4|e?g)|mov(ie)?|msi|msp|pdf|phps|png|ppt(x|m)?|pot(x|m)?|pps(x|m)?|ppam|sld(x|m)?|thmx|qtm?|ra(m|r)?|sea|sit|tar|tgz|torrent|txt|wav|wma|wmv|wpd|xls(x|m|b)?|xlt(x|m)|xlam|xml|z|zip\u0022,\u0022trackUrlFragments\u0022:1},\u0022ajaxPageState\u0022:{\u0022js\u0022:{\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/jquery.cluetip.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.hoverIntent.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.bgiframe.min.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_at_symbol.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_article_reference_popup.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/contrib\\\/google_analytics\\\/googleanalytics.js\u0022:1,\u00220\u0022:1}}});\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Clink 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\u003EMultiple mechanisms that contribute to cardiovascular disease in patients with diabetes mellitus have been identified. Diabetic neuropathy can manifest as cardiac autonomic neuropathy and directly affect heart function. In addition, obstructive sleep apnea is associated with cardiovascular events and death. Hypoglycemia episodes can cause cardiac ischemia, atherothrombosis, and endothelial dysfunction.\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\u003Ecardiovascular disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eobstructive sleep apnea\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ediabetic neuropathy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecardiac autonomic neuropathy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecardiometabolic disorder\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ehyperglycemia\/hypoglycemia\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EOver the last 20 years, the prevalence of diabetes mellitus (DM) in the United States has nearly doubled to 9.3% [Selvin E et al. \u003Cem\u003EAnn Intern Med.\u003C\/em\u003E 2014], with rising prevalence observed in children and adolescents [Dabelea D et al. \u003Cem\u003EJAMA\u003C\/em\u003E. 2014]. Rodica Pop-Busui, MD, PhD, University of Michigan, Ann Arbor, Michigan, USA, discussed the role of diabetic neuropathy on cardiovascular (CV) risk in patients with DM.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003ENeuropathies affect up to 50% of patients with DM [Pop-Busui R et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E. 2013]. The diagnosis of peripheral diabetic neuropathy can be aided by using a simple clinical tool, the Michigan Neuropathy Screening Instrument [Herman WH et al. \u003Cem\u003EDiabet Med.\u003C\/em\u003E 2012; Feldman et al. \u003Cem\u003EDiabetes Care.\u003C\/em\u003E 1994]. In addition, the type of symptoms that a patient experiences can be indicative of the type of nerve fibers that are affected (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). Importantly, the heart is innervated by both sympathetic and parasympathetic nerves.\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\/16530\/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\/16530\/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\/16530\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\u003ESymptoms Indicating Nerve Fiber\u2013Type Involvement\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-5\u0022\u003EDiabetic neuropathy is associated with high morbidity and low quality of life and is an independent predictor of mortality in patients with type 1 DM (T1DM) and type 2 DM (T2DM). For instance, the EURODIAB IDDM Prospective Complications Study [Soedamah-Muthu SS et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E. 2008] reported that both CV autonomic and peripheral neuropathy were associated with similar CV disease (CVD) mortality risk after 7 years of follow-up. An analysis of \u0026gt;\u20058000 patients with T2DM enrolled in the ACCORD trial [Pop-Busui R et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E. 2010] who had valid cardiac autonomic neuropathy (CAN) data found that presence of CAN at baseline was associated with higher all-cause and CVD mortality risk after 3.5 years of follow-up.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003ESimilarly, a post hoc analysis of the ACCORD trial found that all-cause mortality was significantly associated with self-reported history of neuropathy (\u003Cem\u003EP\u003C\/em\u003E\n            \u003Csub\u003EInteraction\u003C\/sub\u003E\n            \u003Cem\u003E\u2005\u003C\/em\u003E=\u2005.0008) [Calles-Escadr\u00f3n J et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E. 2010]. Furthermore, the ADMIRE-HF trial [Jacobson AF et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E. 2010] demonstrated that both cardiac death (\u003Cem\u003Er\u003C\/em\u003E\u2005=\u2005\u20130.83; \u003Cem\u003EP\u2005\u003C\/em\u003E\u0026lt;\u2005.01) and all-cause mortality (\u003Cem\u003Er\u003C\/em\u003E\u2005=\u2005\u20130.89; \u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.001) were highly correlated with lower iodine-123 metaiodobenzylguanidine retention at baseline, an imaging technique to assess integrity of cardiac sympathetic innervation and CAN (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E).\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\/15\/4\/23\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Cardiac Autonomic Neuropathy as Measured by mIBG in the ADMIRE-HF TrialH\/M, heart to mediastinum; mIBG, metaiodobenzylguanidine.Reprinted from J Am Coll Cardiol, 2010;55:2212-2221, Jacobson AF et al, Myocardial iodine-123 meta-iodobenzylguanidine imaging and cardiac events in heart failure. Results of the prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study. Copyright with permission from American College of Cardiology Foundation.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-637105977\u0022 data-figure-caption=\u0022\u0026amp;lt;div xmlns=\u0026amp;quot;http:\/\/www.w3.org\/1999\/xhtml\u0026amp;quot;\u0026amp;gt;Cardiac Autonomic Neuropathy as Measured by mIBG in the ADMIRE-HF TrialH\/M, heart to mediastinum; mIBG, metaiodobenzylguanidine.Reprinted from \u0026amp;lt;em\u0026amp;gt;J Am Coll Cardiol\u0026amp;lt;\/em\u0026amp;gt;, 2010;55:2212-2221, Jacobson AF et al, Myocardial iodine-123 meta-iodobenzylguanidine imaging and cardiac events in heart failure. Results of the prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study. Copyright with permission from American College of Cardiology Foundation.\u0026amp;lt;\/div\u0026amp;gt;\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\/15\/4\/23\/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\/15\/4\/23\/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\/15\/4\/23\/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\/16529\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\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003ECardiac Autonomic Neuropathy as Measured by mIBG in the ADMIRE-HF Trial\u003C\/p\u003E\n               \u003Cp id=\u0022p-8\u0022\u003EH\/M, heart to mediastinum; mIBG, metaiodobenzylguanidine.\u003C\/p\u003E\n               \u003Cp id=\u0022p-9\u0022\u003EReprinted from \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E, 2010;55:2212-2221, Jacobson AF et al, Myocardial iodine-123 meta-iodobenzylguanidine imaging and cardiac events in heart failure. Results of the prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study. Copyright with permission from American College of Cardiology Foundation.\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-10\u0022\u003EEmerging data suggest a link among CAN, left ventricle remodeling, and myocardial dysfunction as reported by several studies. The DCCT\/EDIC study [Pop-Busui R et al. \u003Cem\u003EJ Am Coll Cardiol.\u003C\/em\u003E 2013] found that patients with DM and CAN had significantly greater cardiac output (\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.0001), left ventricular mass (\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.0001), and mass-to-volume ratio (\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.0001), compared with patients who did not have CAN.\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EAbd A. Tahrani, MD, PhD, University of Birmingham, Birmingham, United Kingdom, discussed the possible link between obstructive sleep apnea (OSA) and CVD.\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EOSA has been linked to many factors that are involved in the pathogenesis of CVD risk in population studies, such as hypertension [Peppard PE et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2000], insulin resistance [Tahrani AA et al. \u003Cem\u003ECurr Opin Pulm Med.\u003C\/em\u003E 2013], inflammation [Lavie L. \u003Cem\u003EFront Biosci (Elite Ed)\u003C\/em\u003E. 2012], and obesity.\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EContinuous positive airway pressure (CPAP) has been shown to lower blood pressure (BP) and improve insulin resistance in randomized controlled trials [Hu X et al. \u003Cem\u003EJ Clin Hypertens (Greenwich)\u003C\/em\u003E. 2015; Iftikhar IH et al. \u003Cem\u003EJ Clin Sleep Med.\u003C\/em\u003E 2013]. Limited data also suggest that CPAP can improve insulin resistance and BP in patients with T2DM [Chen L et al. \u003Cem\u003EArch Med Sci\u003C\/em\u003E. 2014; Myhill PC et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E. 2012].\u003C\/p\u003E\n         \u003Cp id=\u0022p-14\u0022\u003EOSA has been more directly linked to CVD. In one study, the cumulative incidence of fatal and nonfatal CV events over an average follow-up of 10.1 years was higher in patients with untreated severe OSA compared with CPAP-treated patients, patients with mild OSA, simple snorers, and the control group [Marin JM et al. \u003Cem\u003ELancet.\u003C\/em\u003E 2005]. In patients with T2DM, OSA was significantly associated with stroke (OR, 2.57; 95% CI, 1.03 to 6.42; \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.04) in a cross-sectional analysis of a subgroup of the Look AHEAD trial [Rice TB et al. \u003Cem\u003ESleep\u003C\/em\u003E. 2012].\u003C\/p\u003E\n         \u003Cp id=\u0022p-15\u0022\u003EOSA has also been shown to be associated with increased oxidative and nitrosative stress and microvascular disease in patients with T2DM [Tahrani AA et al. \u003Cem\u003EAm J Respir Crit Care Med\u003C\/em\u003E. 2012], as well as peripheral neuropathy (60% vs 30%), nephropathy (49% vs 24%), and retinopathy in patients with T2DM in cross-sectional studies [Tahrani AA et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E. 2013; Tahrani AA et al. \u003Cem\u003EAm J Respir Crit Care Med\u003C\/em\u003E. 2012; West SD et al. \u003Cem\u003EDiabet Med.\u003C\/em\u003E 2010]. A recent study also found that patients with T1DM and CAN had a greater prevalence of OSA compared with patients who did not have CAN (67% vs 23%; \u003Cem\u003EP\u2005\u003C\/em\u003E=\u2005.02) [Janovsky CC et al. \u003Cem\u003EFront Endocrinol (Lausanne)\u003C\/em\u003E. 2014].\u003C\/p\u003E\n         \u003Cp id=\u0022p-16\u0022\u003EFurthermore, patients with mild and moderate-to-severe OSA had greater reduction in estimated glomerular filtration rate compared to those without OSA in patients with T2DM over 2.5 years of follow-up [Tahrani AA et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E. 2013]. Current prospective studies and randomized controlled trials are ongoing to assess the relationship between OSA and diabetic microvascular complications and the impact of CPAP in patients with T2DM.\u003C\/p\u003E\n         \u003Cp id=\u0022p-17\u0022\u003EStephen Neil Davis, MBBS, University of Maryland School of Medicine, Baltimore, Maryland, USA, discussed hypoglycemia and its role in severe adverse cardiac events. Multiple studies have demonstrated that hypoglycemia is associated with an increased risk of CV events and all-cause mortality [Khunti K et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E. 2015].\u003C\/p\u003E\n         \u003Cp id=\u0022p-18\u0022\u003EA potential mechanism for this phenomenon is cardiac ischemia, which is associated with hypoglycemic episodes. In a 2003 study of 19 patients with T2DM, 10 out of 54 episodes of hypoglycemia occurred with chest pain, and of these 10 episodes, 4 were associated with significant echocardiograph abnormalities (\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.01).\u003C\/p\u003E\n         \u003Cp id=\u0022p-19\u0022\u003EOther potential mechanisms are atherothrombosis and endothelial dysfunction. A recent study found that acute and repeated hypoglycemia resulted in increased levels of markers of atherothrombosis, including vascular cell adhesion protein 1, P-selectin, interleukin 6, and TNF-\u03b1 [Joy NG et al. \u003Cem\u003EDiabetes\u003C\/em\u003E. 2015]. In addition, hypoglycemia resulted in increased levels of plasminogen activator inhibitor 1 and thrombin-antithrombin complex, as well as decreased flow-mediated dilation via endogenous and exogenous nitric oxide\u2013mediated vasodilation.\u003C\/p\u003E\n         \u003Cp id=\u0022p-20\u0022\u003ESeveral agents are under investigation to determine their role in the counterregulatory response during hypoglycemia, including fructose [Gabriely I, Shamoon H. \u003Cem\u003EDiabetes\u003C\/em\u003E. 2005], naloxone [Vele S et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E. 2011], dehydroepiandrostenedione, and fluoxetine [Briscoe VJ et al. \u003Cem\u003EDiabetes\u003C\/em\u003E. 2008].\u003C\/p\u003E\n         \u003Cp id=\u0022p-21\u0022\u003EIn conclusion, there are multiple mechanisms that are attributed to CVD in patients with DM. In a direct role, neuropathy can lead to CAN and directly affect heart function. In an indirect role, patients with DM and OSA are at an increased risk of CV events and CV death. In addition, patients with OSA are more likely to experience diabetic neuropathy compared with patients who do not have OSA. Finally, hypoglycemic episodes can cause cardiac ischemia and lead to atherothrombosis and endothelial dysfunction.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\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\/15\/4\/23.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?nzln31\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?nzln31\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?nzln31\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}