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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\u003ENew-onset diabetes after transplantation (NODAT) is recognized as one of the major medical complications of solid-organ transplantation. A spectrum of problems is attributed to NODAT, including impaired graft function, infectious complications, patient inconvenience, and increased costs, as well as patient mortality [Woodward RS et al. \u003Cem\u003EAm J Transplant\u003C\/em\u003E 2003].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EPrevention \u0026amp; Screening\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHyperglycemia\/Hypoglycemia\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ENew-onset diabetes after transplantation (NODAT) is recognized as one of the major medical complications of solid-organ transplantation. A spectrum of problems is attributed to NODAT, including impaired graft function, infectious complications, patient inconvenience, and increased costs, as well as patient mortality [Woodward RS et al. \u003Cem\u003EAm J Transplant\u003C\/em\u003E 2003].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EHowever, NODAT is not the same as diabetes mellitus. It has a different pathophysiology and disparate risk factors and treatment options and is associated with a greater risk of diabetic complications [Burroughs TE et al. \u003Cem\u003ETransplantation\u003C\/em\u003E 2007].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EGiven the considerable morbidity and mortality of NODAT, efforts are underway to identify risk factors and preventive approaches. However, there is no clinically validated tool or questionnaire for predicting the risk of developing NODAT.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003ETwo of the strongest, nonmodifiable risk factors are age and ethnicity, particularly African-Caribbeans and Hispanics. Others include human leukocyte antigen (HLA) system mismatches in kidney transplantation, with certain HLA types serving as independent predictors for the development of NODAT. There is also emerging interest in genetic susceptibilities, and some data suggest that deficiencies in the innate immune system may be related to an increased risk [Sharif A et al. \u003Cem\u003ENat Rev Nephrol\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EModifiable risk factors for the development of NODAT include elevated pretransplantation fasting glucose, which is associated with an increased risk 1-year posttransplant and hyperglycemia in the immediate postoperative period, even transient hyperglycemia [Chakkera HA et al. \u003Cem\u003EClin J Am Soc Nephrol\u003C\/em\u003E 2010; Chakkera HA et al. \u003Cem\u003EClin J Am Soc Nephrol\u003C\/em\u003E 2009]. The issue of transient hyperglycemia is important, because 66% of nondiabetics are discharged on insulin.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EThe use of an oral glucose tolerance test (OGTT) is beneficial for pretransplant risk stratification, since impaired glucose tolerance pretransplantation is predictive for posttransplant hyperglycemia [Bergrem HA et al. \u003Cem\u003ENephrol Dial Transplant\u003C\/em\u003E 2010]. The use of the OGTT is also important for predicting the risk of NODAT posttransplant, as evidence suggests that this measurement can identify more patients with NODAT than fasting glucose tests alone [Delgado P et al. \u003Cem\u003EClin J Am Soc Nephrol\u003C\/em\u003E 2008; Sharif A et al. \u003Cem\u003ETransplantation\u003C\/em\u003E 2006].\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EWhile there are advantages that are associated with HbA1C use in the transplantation setting, there are also caveats that are associated with its use, including the lack of validation in the transplantation setting, the influence of posttransplantation anemia, and the myelotoxicity of immunosuppressants, all of which can affect accuracy [Sharif A et al. \u003Cem\u003EJ Am Soc Nephrol\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EImmunosuppressive agents represent another modifiable risk factor for NODAT. While many are diabetogenic, some, including mycophenolate mofetil, azathioprine, and biological induction agents, are not [Sharif A et al. \u003Cem\u003ENat Rev Nephrol\u003C\/em\u003E 2010]. Other modifiable risk factors include obesity; biochemical abnormalities, such as posttransplantation hypomagnesemia, uric acid, vitamin D deficiency, and renal or renal graft function; and the use of antihypertensives [Armstrong KA et al. \u003Cem\u003ENephrology\u003C\/em\u003E 2005; Van Laecke A et al. Am J \u003Cem\u003ETransplant\u003C\/em\u003E 2009; Sharif A, et al. \u003Cem\u003EAm J Transplant\u003C\/em\u003E 2009; Hjelmesaeth J et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2001].\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EStudies are underway to identify the potential protective effects of pharmacological prophylaxis with sitagliptin to prevent NODAT following kidney transplantation.\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ETreating NODAT\u003C\/h2\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EMost of the current data on NODAT focus on immunosuppressant therapies and prevention strategies. However, there are little data on the optimal treatment for this condition. Current goals for therapy are based on American Diabetes Association guidelines for nontransplant diabetics. They include target HbA1C of \u0026lt;7% following transplant, premeal glucose of 90\u2013130 mg\/dL, postprandial glucose of \u0026lt;180 mg\/dL, blood pressure of \u0026lt;130\/80 mm Hg, low-density lipoprotein (LDL) cholesterol of \u0026lt;100 mg\/dL, high-density lipoprotein (HDL) cholesterol of \u0026gt;40 mg\/dL, and triglycerides of \u0026lt;150 mg\/dL [Reynolds LR et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2001].\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003ELisa Tannock, MD, University of Kentucky, Lexington, Kentucky, USA, discussed treatment options for NODAT. Dr. Tannock\u0027s group does not utilize oral antidiabetic agents for hospitalized patients\u2014only insulin. Patients who receive intravenous (IV) nutrition are managed on IV insulin, while those who are able to eat receive basal\/bolus insulin.\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EIn the outpatient setting, patients may be managed with either insulin or oral agents. Patients with blood glucose levels \u0026gt;300 mg\/dL (16 mmol\/L) begin on insulin, with the regimen dependent on the patient. The two algorithms that are used are either 10 units twice daily titrated by 2 units every 1 to 2 days or a body weight dosing formula. In extremely obese patients, body weight dosing is used. Patients with more moderate hyperglycemia receive education and evaluation, possibly leading to adjustment of their immunosuppressive agents and insulin or oral therapies, as needed.\u003C\/p\u003E\n         \u003Cp id=\u0022p-14\u0022\u003EWhen using oral antidiabetic agents, metformin is affordable, effective, and well tolerated, with no associated weight gain or hyperglycemia. Although there are little data on its use in the transplant population, it appears safe in patients who do not have renal insufficiency, significant liver disease, or congestive heart failure.\u003C\/p\u003E\n         \u003Cp id=\u0022p-15\u0022\u003EThe thiazolidinediones (TZD) appear to be safe for use in patients with chronic kidney disease; however, they should be used cautiously in patients with liver dysfunction. It is important to note that cardiovascular risk that is associated with TZD use is unclear, and TZD therapy may increase the risk of fractures and may result in weight gain and edema.\u003C\/p\u003E\n         \u003Cp id=\u0022p-16\u0022\u003EA retrospective study that addressed the duration and efficacy of TZDs versus metformin in transplant patients found that while HbA1C levels were similar between the two groups, patients who were on TZDs had a greater duration of glycemic control (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). However, they ultimately needed further treatment as the study progressed. Additionally, metformin demonstrated a greater effect on glomerular filtration rate (GFR) levels, raising concerns about its use in patients with renal disease [Kurian B et al. \u003Cem\u003EEndocr Pract\u003C\/em\u003E 2008].\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\/10\/9\/33\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Metformin Versus TZD in Renal Transplant Recipients.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1359220493\u0022 data-figure-caption=\u0022Metformin Versus TZD in Renal Transplant Recipients.\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\/33\/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\/33\/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\/33\/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\/11560\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-17\u0022 class=\u0022first-child\u0022\u003EMetformin Versus TZD in Renal Transplant Recipients.\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from L. Tannock, 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-18\u0022\u003ESecretagogues are also effective in NODAT patients, but these compounds require more frequent dosing and are metabolized via CYP3A4, raising concerns regarding drug interactions. There are little data on other oral hyperglycemic options in this population.\u003C\/p\u003E\n         \u003Cp id=\u0022p-19\u0022\u003EIn conclusion, it is clear that more research is needed as to the best approach to prevent and treat NODAT. Greater collaborations between diabetologists and transplant physicians are required to ensure the delivery of optimum care.\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\/33.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"}