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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\u003EInsulin is released continuously by the pancreas at a nearly constant rate between meals and in the fasting state (basal insulin secretion). This article discusses the data on various basal insulins, as well as evolution of rapid-acting insulin, limitations of current insulin preparations, and pipeline products.\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\u003EInsulin\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EBasal Insulin\u003C\/h2\u003E\n         \u003Cp id=\u0022p-2\u0022\u003EInsulin is released continuously by the pancreas at a nearly constant rate between meals and in the fasting state (basal insulin secretion). The pivotal role of basal insulin is to restrain the release of glucose from the liver and free fatty acids from adipose tissue, thus preventing hyperglycemia and ketosis [Bolli GB et al. \u003Cem\u003EDiabetes Technol Ther\u003C\/em\u003E 2011]. Geremia B. Bolli, MD, University of Perugia, Perugia, Italy, presented data on various basal insulins.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003ENeutral protamine Hagedorn (NPH) insulin and NPH-based insulin mixtures have early peak effects and a relatively short duration of action. They carry a risk of nocturnal hypoglycemia and fasting hyperglycemia, respectively, after the evening injection [Bolli GB et al. \u003Cem\u003EDiabetes Technol Ther\u003C\/em\u003E 2011] (\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\/12\/10\/22\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022NPH and NPH-Based Insulin Mixtures Have Early Peak Effects and Relatively Short Duration of Action.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-984101798\u0022 data-figure-caption=\u0022NPH and NPH-Based Insulin Mixtures Have Early Peak Effects and Relatively Short Duration of Action.\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\/12\/10\/22\/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\/12\/10\/22\/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\/12\/10\/22\/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\/12739\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\u003ENPH and NPH-Based Insulin Mixtures Have Early Peak Effects and Relatively Short Duration of Action.\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from GB Bolli, 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-5\u0022\u003ECompared with NPH insulin, glargine provides greater metabolic activity and superior glucose control for up to 32 hours [Lucidi P et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2011]. Glargine is a peakless insulin that lasts nearly 24 hours, has lower intersubject variability than NPH insulin, and closely mimics continuous subcutaneous insulin infusion (CSII). The gold standard means of basal insulin replacement [Lepore M et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2000], CSII delivers rapid-acting insulin that mirrors the endogenous insulin pattern of the pancreas.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EOnly long-acting analogs, such as glargine (\u0026gt;24 hours in duration, once a day) and detemir (\u0026lt;24 hours in duration, once or twice a day), should be used as a basal insulin in type 1 diabetes in combination with mealtime rapid-acting analogs [Bolli GB. \u003Cem\u003EDiabetes Technol Ther\u003C\/em\u003E 2011]. The preferred means of delivery is CSII.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EDetemir is associated with a higher insulin dose compared with insulin glargine across a wide body mass index range [Holleman F et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2011]. CSII is a superior option, owing to better reproducibility or subcutaneous absorption of soluble insulin. Although CSII is not superior to multiple daily insulin injections in the general population of people with type 1 diabetes, it might be indicated in subsets of those with type 1 diabetes [Bolli GB et al. \u003Cem\u003EDiabetes Technol Ther\u003C\/em\u003E 2011].\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EBasal insulin degludec, which is still under development, is an ultra-long-acting basal insulin [Heller S. \u003Cem\u003ELancet\u003C\/em\u003E 2012]. Its pharmacokinetic profile predicts a sustained effect (\u0026gt;24 hours), low variability in subcutaneous absorption, and a low rate of hyperglycemia. Day-to-day variability in glucose-lowering effect is 4 times lower with degludec versus glargine [Heise T et al. \u003Cem\u003EDiabetes Obes Metab\u003C\/em\u003E 2012].\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EA novel basal insulin that is under development, LY2605541, is engineered to be large in size, thereby delaying insulin absorption, reducing clearance, and resulting in prolonged duration of action [Hansen RJ et al. ADA 2012 Abstract 896-P]. Questions that remain on LY2605541 include its pharmacokinetic profile in type 1 diabetes, day-to-day reproducibility, lipid\/hepatic mechanism and weight loss in the face of improved glycemic control, and titration.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EDr. Bolli said the replacement of basal insulin is fundamental to insulin treatment of types 1 and 2 diabetes, and substitution of basal insulin becomes increasingly more important and challenging as \u03b2-cell mass or function deteriorates over time.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ENewer Bolus Insulins\u003C\/h2\u003E\n         \u003Cp id=\u0022p-11\u0022\u003ELuigi F. Meneghini, MD, University of Miami Miller School of Medicine, Miami, Florida, USA, discussed the evolution of rapid-acting insulin, limitations of current insulin preparations, and pipeline products.\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EHome et al. recently reported [\u003Cem\u003EDiabetes Obes Metab\u003C\/em\u003E 2012] that postprandial glucose excursions can inhibit achievement of good glycemic control and possibly have an effect on the risk of vascular comorbidities. Rapid-acting analogs offer an earlier onset and peak of biologic activity, a shorter duration of action, and less biologic variability (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E), potentially leading to more physiologic insulin insulin replacement and better overall control than with human insulin.\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\/12\/10\/22\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Potential Advantages of Rapid-Acting Insulin Analogs.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-984101798\u0022 data-figure-caption=\u0022Potential Advantages of Rapid-Acting Insulin Analogs.\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\/12\/10\/22\/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\/12\/10\/22\/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\/12\/10\/22\/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\/12740\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-13\u0022 class=\u0022first-child\u0022\u003EPotential Advantages of Rapid-Acting Insulin Analogs.\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from LF Meneghini, 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-14\u0022\u003EA Cochrane review of the effects of short-acting insulin analogs versus regular insulin, however, suggested only a modest benefit of short-acting insulin analogs in the majority of patients treated with insulin [Siebenhofer A et al. \u003Cem\u003ECochrane Database Syst Rev\u003C\/em\u003E 2006]. Clearly the timing of insulin bolus to meal is an important determinant of post-prandial glycemic control, and should favor rapid-acting insulin analogs. It is clear, from a study on the optimal timing of bolus administration in relation to meal consumption in adolescents and adults with type 1 diabetes, that a bolus of rapid-acting insulin prior to a meal results in significantly better postprandial glucose control than when the meal insulin bolus is given just prior to the meal or 20 minutes after meal initiation. [Cobry E et al. \u003Cem\u003EDiabetes Technol Ther\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003Cp id=\u0022p-15\u0022\u003EInsulin analogs are absorbed more quickly than human insulin in normal-weight healthy subjects or lean subjects with type 1 diabetes. However, most patients with type 2 diabetes using insulin are distinctly overweight or obese and require much larger insulin dosages [Lane WS et al. \u003Cem\u003EEndocr Pract\u003C\/em\u003E 2009]. Gagnon-Auger et al. [\u003Cem\u003EDiabetes Care\u003C\/em\u003E 2010] found that absorption of even a rapid-acting insulin analog such as lispro is substantially delayed and biologic activity considerably lower in obese subjects with type 2 diabetes.\u003C\/p\u003E\n         \u003Cp id=\u0022p-16\u0022\u003EThere are a number of innovative technologies being applied to provide a more physiologic insulin action profile. One such approach is the use of a fully human recombinant DNA-derived hyaluronidase enzyme (rHuPH20), which reduces resistance to bulk fluid flow following drug injection (insulin) and promotes drug dispersion to allow exposure to a greater capillary bed area. This approach accelerates absorption and peak biologic activity, as well as shortens the duration of action of either regular insulin or rapid-acting insulin analog preparations. [Frost GI. E\u003Cem\u003Expert Opin Drug Deliv\u003C\/em\u003E 2007].\u003C\/p\u003E\n         \u003Cp id=\u0022p-17\u0022\u003EAnother approach\u2014inhaled insulin delivery\u2014is generally well-tolerated and appears to be safe, at least in the short term [Muchmore DB, Gates JR. Diabetes Obes Metab 2006]. Inhaled insulin offers an alternative noninvasive option for premeal insulin administration, with glycemic efficacy slightly less than subcutaneous regular insulin and increased acceptability [Ceglia L et al. Ann Intern Med 2006].\u003C\/p\u003E\n         \u003Cp id=\u0022p-18\u0022\u003EA randomized, open-label, parallel-group study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00309244\u0026amp;atom=%2Fspmdc%2F12%2F10%2F22.atom\u0022\u003ENCT00309244\u003C\/a\u003E] to assess the efficacy and safety of prandial Technosphere\u00ae inhaled insulin compared with twice-daily biaspart insulin found that change in HbA1C with inhaled insulin plus insulin glargine (0.68%; SE, 0.077; 95% CI, 0.83 to 0.53) was similar and noninferior to that with biaspart insulin (0.76%; SE, 0.071; 0.90 to 0.62).\u003C\/p\u003E\n         \u003Cp id=\u0022p-19\u0022\u003EPatients had significantly less weight gain (p\u0026lt;0.05) and a reduced incidence of mild-to-moderate and severe hypoglycemic events on inhaled insulin plus insulin glargine than on biaspart insulin. The safety and tolerability profile was similar for both treatments, although there was an increased occurrence of cough and change in pulmonary function in the group that received inhaled insulin plus insulin glargine [Rosenstock J et al. \u003Cem\u003ELancet\u003C\/em\u003E 2010]. Concerns with respect to chronic lung exposure of high insulin concentrations still need to be carefully evaluated.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2012 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\/12\/10\/22.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?nznez2\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?nznez2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}