Clinical and genetic risk factors for posttransplant diabetes mellitus in adult renal transplant recipients treated with tacrolimus.
BACKGROUND
The present study investigated the incidence of posttransplant diabetes mellitus (PTDM) and calculated the risk of developing PTDM under a tacrolimus-based immunosuppression based on clinical characteristics, tacrolimus pharmacokinetics, and genetic polymorphisms related to tacrolimus pharmacokinetics or diabetes mellitus.


METHODS
Seventy nondiabetic adult kidney recipients were studied. Patients with continuous high plasma glucose levels, over 6.5 mg/dl of hemoglobin A1c, or requiring insulin and/or oral antidiabetic agents for more than 3 months after transplantation 6 months postoperatively were diagnosed as having PTDM. Twelve genomic polymorphisms were assessed.


RESULTS
Six months after transplantation, 10 recipients (14.3%) developed PTDM. Positive risk factors were age (P=0.019) and body mass index (P=0.038). There were no significant differences in acute rejection rate, total steroid doses, tacrolimus pharmacokinetics or its related to genetic polymorphisms between the two groups. The frequency of PTDM was significantly higher in patients with the vitamin D receptor (VDR) TaqI t allele than in those with the TT genotype (P=0.013). On multivariate analysis, age over 50 years (odds ratio 9.28, P=0.003) and the presence of the VDR TaqI t allele (odds ratio 7.05, P=0.048) were correlated with the development of PTDM.


CONCLUSIONS
The incidence of PTDM was 14.3% in our cohort. Age over 50 years was a risk factor. The presence of the VDR TaqI t allele may also be a risk factor for PTDM, suggesting that genotyping of diabetes-related polymorphisms is a possible method of predicting a patient's risk for developing PTDM and would be a valuable asset in selecting appropriate immunosuppressive regimens for individuals.
Numakura
Kazuyuki
K
Department of Urology, Akita University School of Medicine, Akita, Japan.
Satoh
Shigeru
S
Tsuchiya
Norihiko
N
Horikawa
Yohei
Y
Inoue
Takamitsu
T
Kakinuma
Hideaki
H
Matsuura
Shinobu
S
Saito
Mitsuru
M
Tada
Hitoshi
H
Suzuki
Toshio
T
Habuchi
Tomonori
T
D052242:Adiponectin / Q000235:genetics; D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D005260:Female; D019450:Genes, MDR / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D007473:Ion Channels; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics; D015999:Multivariate Analysis; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D047495:PPAR gamma / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics; D012307:Risk Factors; D016559:Tacrolimus / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000071246:Uncoupling Protein 2
C499918:ADIPOQ protein, human; D052242:Adiponectin; D007166:Immunosuppressive Agents; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D047495:PPAR gamma; D018167:Receptors, Calcitriol; D000071246:Uncoupling Protein 2; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D007703:Peptidyl-Dipeptidase A; D009173:Mycophenolic Acid; D001379:Azathioprine; D016559:Tacrolimus