New-Onset Diabetes after Kidney Transplantation

Rodrigo, Emilio; Fernández‐Fresnedo, Gema; Valero, Rosalía; Ruiz, J.C.; Piñera, Celestino; Palomar, Rosa; González–Cotorruelo, Julio; Gómez-Alamillo, C.; Arias, Manuel

doi:10.1681/asn.2006080929

Cited by 155 publications

(119 citation statements)

References 37 publications

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“…32,35,36 HapMap data show that the protective W allele frequency was much lower in the African group than in other ethnic populations (the W allele frequency was 25% in a group of Caucasian Americans with European ancestry, 48% in a Han Chinese population and 6% in a Yoruba population in Nigeria). 37 These data may also support the association of W325 with a low incidence of PTDM.…”

Section: Discussionmentioning

confidence: 97%

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A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion

et al. 2010

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SLC30A8 encodes the b-cell-specific zinc transporter-8 (ZnT-8) expressed in insulin secretory granules. The single-nucleotide polymorphism rs13266634 of SLC30A8 is associated with susceptibility to post-transplantation diabetes mellitus (PTDM). We tested the hypothesis that the polymorphic residue at position 325 of ZnT-8 determines the susceptibility to cyclosporin A (CsA) suppression of insulin secretion. INS (insulinoma)-1E cells expressing the W325 variant showed enhanced glucose-stimulated insulin secretion (GSIS) and were less sensitive to CsA suppression of GSIS. A reduced number of insulin granule fusion events accompanied the decrease in insulin secretion in CsA-treated cells expressing ZnT-8 R325; however, ZnT-8 W325-expressing cells exhibited resistance to the dampening of insulin granule fusion by CsA, and transported zinc ions into secretory vesicles more efficiently. Both tacrolimus and rapamycin caused similar suppression of GSIS in cells expressing ZnT-8 R325. However, cells expressing ZnT-8 W325 were resistant to tacrolimus, but not to rapamycin. The Down's syndrome candidate region-1 (DSCR1), an endogenous calcineurin inhibitor, overexpression and subsequent calcineurin inhibition significantly reduced GSIS in cells expressing the R325 but not the W325 variant, suggesting that differing susceptibility to CsA may be due to different interactions with calcineurin. These data suggest that the ZnT-8 W325 variant is protective against CsA-induced suppression of insulin secretion. Tolerance of ZnT-8 W325 to calcineurin activity may account for its protective effect in PTDM.

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Section: Discussionmentioning

confidence: 97%

“…However, the definite involvement of rapamycin in PTDM is still under investigation. 32,33 Recently, the suppression of carbohydrate metabolism by rapamycin was suggested as a candidate mechanism for the inhibition of insulin secretion. 34 However, the mechanism of action of rapamycin in the insulin secretory pathway is largely unknown.…”

Section: Discussionmentioning

confidence: 99%

A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion

et al. 2010

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“…osttransplantation diabetes mellitus (PTDM) is a serious metabolic complication and is associated with cardiovascular morbidity and mortality (1)(2)(3). Patients with PTDM have an increased risk for long-term cardiovascular events of up to 3.27 times compared with those without PTDM (4).…”

mentioning

confidence: 99%

A Polymorphism in the Zinc Transporter Gene SLC30A8 Confers Resistance Against Posttransplantation Diabetes Mellitus in Renal Allograft Recipients

Kang

Kim

et al. 2008

Diabetes

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OBJECTIVE—Posttransplantation diabetes mellitus (PTDM) is a major metabolic complication in renal transplant recipients, and insulin secretory defects play an important role in the pathogenesis of PTDM. The R325W (rs13266634) nonsynonymous polymorphism in the islet-specific zinc transporter protein gene, SLC30A8, has been reported to be associated with type 2 diabetes and possibly with a defect in insulin secretion. This study investigated the association between genetic variations in the SLC30A8 gene and PTDM in renal allograft recipients. RESEARCH DESIGN AND METHODS—A total of 624 unrelated renal allograft recipients without previously diagnosed diabetes were enrolled. Rs13266634 was genotyped in the cohort, which consisted of 174 posttransplantation diabetic patients and 450 non-posttransplantation diabetic subjects. The genotyping of the SLC30A8 polymorphism was performed using real-time PCR. RESULTS—The prevalence of PTDM was 33.8% in patients carrying the R/R genotype, 26.8% in patients with the R/W genotype, and 19.8% in patients with the W/W genotype. There was a strong association between the number of W-alleles and PTDM risk reduction (P for trend = 0.007). Patients with at least one T-allele showed a decreased risk of PTDM compared with those with the R/R genotype (R/W, risk ratio [RR] 0.78, P = 0.126; W/W, RR 0.52, P = 0.007). The effect of the SLC30A8 genotype remained significant after adjustments for age, sex, body weight gain, and type of immunosuppressant (R/W, hazard ratio [HR] 0.77, P = 0.114; W/W, HR 0.58, P = 0.026). CONCLUSIONS—These data provide evidence that the SLC30A8 rs13266634 gene variation is associated with protection from the development of PTDM in renal allograft recipients.

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“…흑인과 히스패닉계 인종은 동양인과 백인에 비해 이식 후 당뇨병의 위험이 더 높은 것으로 알려져 있다 [2,10,12,13]. 한 연구에 따르면 신장이식을 받은 환자의 11.6%에 서 이식 후 당뇨병이 발생하였는데, 이 중 히스패닉계 인 종은 21.3%, 흑인은 19.8%, 동양인은 4.8%의 발병률을 보 였다 [8].…”

Section: 인종unclassified

Management of Diabetes in Organ Transplant Patients

Yun

Kang

2014

J Korean Diabetes

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New onset diabetes after transplantation (NODAT) is a common complication after solid-organ transplantation and is associated with increased cardiovascular morbidity, mortality, and graft loss. The risk factors for NODAT include older age, ethnicity, genetic factors,obesity, family history of diabetes, hepatitis C virus infection, and immunosuppressant use (corticosteroids, calcineurin inhibitors, and mTOR inhibitor). Management of NODAT must be considered at the pre-transplantation stage in order to properly screen high-risk patients. Although NODAT management is similar to that of general type 2 diabetes, some specific considerations must be made in NODAT management, including the interactions between anti-diabetes medication and immunosuppressive agents. (J Korean Diabetes 2014;15:134-141)

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New-Onset Diabetes after Kidney Transplantation

Cited by 155 publications

References 37 publications

A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion

A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion

A Polymorphism in the Zinc Transporter Gene SLC30A8 Confers Resistance Against Posttransplantation Diabetes Mellitus in Renal Allograft Recipients

Management of Diabetes in Organ Transplant Patients

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