Diabetes mellitus after transplant: relationship to pretransplant glucose metabolism and tacrolimus or cyclosporine A-based therapy

Sato, Tetsuhiko; Inagaki, Akemi; Uchida, Kazuharu; Ueki, Tsuneo; Goto, Norihiko; Matsuoka, Susumu; Katayama, Akio; Haba, T; Tominaga, Yoshihiro; Okajima, Yoshiki; Ohta, Kimiko; Suga, Hidetaka; Taguchi, Seiko; Kakiya, Satoshi; Itatsu, Takeharu; Kobayashi, Takaaki; Nakao, Akimasa

doi:10.1097/01.tp.0000084295.67371.11

Cited by 56 publications

(30 citation statements)

References 22 publications

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“…The incidence of NODM is similar to the relatively few studies also applying strict diagnostic criteria of diabetes before and after transplantation, with incidences ranging from 18% to 24% (7,13,14). We confirmed the earlier documented high prevalence of glucometabolic changes in nondiabetic patients with stage 5 chronic kidney disease (22).…”

Section: Discussionsupporting

confidence: 88%

New-Onset Diabetes Mellitus after Kidney Transplantation in Denmark

Hornum

Jørgensen²,

Hansen³

et al. 2010

Clinical Journal of the American Society of Nephrology

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Background and objectives: This study aimed to investigate the development of new-onset diabetes mellitus (NODM) in a prospective study of 97 nondiabetic uremic patients.Design, setting, participants, & measurements: Included were 57 kidney recipients (Tx group, age 39 ؎ 13 years) and 40 uremic patients remaining on the waiting list for kidney transplantation (uremic controls, age 47 ؎ 11 years). All were examined at baseline before possible transplantation and after 12 months. The prevalence of diabetes, prediabetes, insulin sensitivity index (ISI), and insulin secretion index (Isecr) were estimated using an oral glucose tolerance test with measurements of plasma glucose and plasma insulin.Results: One year after transplantation NODM was present in 14% (8 of 57) compared with 5% (2 of 40) in the uremic control group (P ‫؍‬ 0.01). ISI in the Tx group deteriorated from 6.8 ؎ 3.9 before transplantation to 4.9 ؎ 2.8 at 12 months after transplantation (P ‫؍‬ 0.005), and a slight increase in Isecr from 37 ؎ 19 to 46 ؎ 22 (P ‫؍‬ 0.02) was seen. No significant changes occurred in the uremic controls (ISI was 7.9 ؎ 5 and 8.5 ؎ 5, and Isecr was 31 ؎ 17 and 28 ؎ 15). Using multivariate ordinal logistic regression, pre-Tx ISI and age predicted NODM (odds ratios: 0.82, P ‫؍‬ 0.01 and 1.06, P ‫؍‬ 0.02, respectively).Conclusions: One year after kidney transplantation, NODM was present in 14% of patients. This was mainly caused by an increase in insulin resistance and was observed despite improvement in insulin secretion.

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Section: Discussionsupporting

confidence: 88%

New-Onset Diabetes Mellitus after Kidney Transplantation in Denmark

Hornum

Jørgensen²,

Hansen³

et al. 2010

Clinical Journal of the American Society of Nephrology

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“…The reason that our results suggest a potentially protective effect of higher CsA dosages remains unclear. There is some evidence that CsA but not Tac is associated with higher insulin-to-glucose ratios that may reflect increased insulin production in patients who are at particular risk for NOD (37). The effect of these CNI on both islet and ␤ cells varies (8).…”

Section: Discussionmentioning

confidence: 99%

Influence of Early Posttransplantation Prednisone and Calcineurin Inhibitor Dosages on the Incidence of New-Onset Diabetes

Burroughs¹,

Lentine²,

Takemoto³

et al. 2007

Clinical Journal of the American Society of Nephrology

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“…Shapiro et al (2000) have developed a glucocorticoid-free immunosuppressive protocol that includes sirolimus, low-dose tacrolimus, and a monoclonal antibody against the interleukin-2 receptor (daclizumab) for islet transplantation in patients with brittle type 1 diabetes. The addition of mycophenolate mofetil to immunosuppressive regimens has been shown to reduce even further the incidence of rejection following pancreas or islets transplantation (Sato et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Pancreatic β-cells expressing GLP-1 are resistant to the toxic effects of immunosuppressive drugs

D’Amico¹,

Hui²,

Khoury³

et al. 2005

Journal of Molecular Endocrinology

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Glucose intolerance is often observed after pancreatic islet cell transplantation. The administration of immunosuppressive agents (ISD), necessary to avoid tissue rejection, is in part responsible for hyperglycemia. To investigate whether mouse insulinoma (MIN6) cells transfected with the glucagon like peptide-1 (GLP-1) fragment of the proglucagon gene (RIP/GLP-1 MIN6 cells) are resistant to the toxicity derived from the administration of ISD. RIP/GLP-1 MIN6 cells, as well as parental MIN6 cells, were exposed to a cocktail of ISD. The secretion of insulin and the expression of apoptosis-related proteins were investigated by RIA and western blot analysis. Cell apoptosis was quantified by FACS analysis. Finally, to study whether the antiapoptotic action of GLP-1 was a function of its effect on insulin secretion, or rather it was a direct effect of GLP-1, cells were cultured with or without diazoxide or exendin-9. GLP-1 improved the functional activity and the viability of cells exposed to ISD. The insulin secretion of RIP/GLP-1 MIN6 cells after exposure to ISD was preserved. The expression of GLP-1 by -cells reduced the number of apoptotic cells and increased the expression of the antiapoptotic protein Bcl-2. GLP-1 also decreased the abundance of the proapoptotic markers PARP-p85 and Smac/Diablo. Treatment of cells with the diazoxide did not abolish the protective advantage that cells transfected with GLP-1 had; conversely the exposure of cells to exendin-9 was associated with a restored susceptibility to apoptosis. This report demonstrates that GLP-1 is capable of preserving -cell function and protecting cells from apoptotic cell death.

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Diabetes mellitus after transplant: relationship to pretransplant glucose metabolism and tacrolimus or cyclosporine A-based therapy

Cited by 56 publications

References 22 publications

New-Onset Diabetes Mellitus after Kidney Transplantation in Denmark

New-Onset Diabetes Mellitus after Kidney Transplantation in Denmark

Influence of Early Posttransplantation Prednisone and Calcineurin Inhibitor Dosages on the Incidence of New-Onset Diabetes

Pancreatic β-cells expressing GLP-1 are resistant to the toxic effects of immunosuppressive drugs

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