title: Tacrolimus decreases insulin sensitivity without reducing fasting insulin concentration: a 2-year follow-up study in kidney transplant recipients.
abstract: New Onset Diabetes after Transplantation (NODAT) is defined as sustained hyperglycemia developing in patients without diabetes history before transplantation. A cohort study was performed to access the effects of tacrolimus on insulin secretion and insulin sensitivity and consequently in the development of NODAT in kidney transplant recipients. Then, we further investigated the association between NODAT and single-nucleotide polymorphisms of IRS-1 and IRS-2 in renal allograft recipients. One hundred and fifty-eight kidney transplant patients, receiving tacrolimus as the base immunosuppressant, were divided into two groups: with or without NODAT. Plasma levels of fasting insulin concentration (FINS) and C-peptide were determined by enhanced chemiluminescence immunoassay and ADVIA Centaur C peptide assay, respectively. The genotypes of Gly1057Asp in IRS-2 and Gly972Arg in IRS-1 were detected through polymerase chain reaction fragment length polymorphism in NODAT and non-NODAT patients. It was found that the concentrations of fasting plasma insulin and C-peptide in NODAT and non-NODAT patients treated with tacrolimus were higher than that in healthy volunteers (p < 0.05). Fasting plasma insulin concentration in NODAT was significantly elevated compared with than that in non-NODAT group (p < 0.05). But there are no statistical differences in fasting plasma C-peptide concentrations between NODAT and non-NODAT groups. The allele and genotype frequencies of IRS-2 Gly1057Asp and IRS-1 Gly972Arg in NODAT patients were not significantly different from non-NODAT patients (p > 0.05). In conclusion, insulin resistance is the primary cause of tacrolimus-induced NODAT. The IRS-2 Gly1057Asp and IRS-1 Gly972Arg genotypes are not related to NODAT.
authors: Clinical Pharmacy and Pharmacology Research Institute, The Third Xiangya Hospital of Central South University , Changsha, Hunan , PR China .
authors: Qing-Jie
authors: QJ
authors: Chen
authors: Jing
authors: J
authors: Li
authors: Shan-Ru
authors: SR
authors: Zuo
authors: Ya-Ping
authors: YP
authors: Zhang
authors: Su-Jie
authors: SJ
authors: Jia
authors: Hong
authors: H
authors: Yuan
authors: Shi-Kun
authors: SK
authors: Liu
authors: Ke
authors: K
authors: Cheng
authors: Ying-Zi
authors: YZ
authors: Ming
authors: Xiao-Cong
authors: XC
authors: Zuo
authors: Ai-Jing
authors: AJ
authors: Luo
authors: Wen-Zhao
authors: WZ
authors: Xie
authors: Jing-Jing
authors: JJ
authors: Cai
authors: Meng
authors: M
authors: Yang
authors: Jiang-Lin
authors: JL
authors: Wang
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000139:chemically induced* / Q000453:epidemiology* / Q000235:genetics; D005215:Fasting / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D016030:Kidney Transplantation; D008297:Male; D011183:Postoperative Complications / Q000139:chemically induced* / Q000453:epidemiology* / Q000235:genetics; D012307:Risk Factors; D016559:Tacrolimus / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D007328:Insulin; D016559:Tacrolimus
keywords: IRS-1; IRS-2; PTDM; SNP; TAC