Is there a genetic predisposition to new-onset diabetes after kidney transplantation?

Kidney transplant recipients may develop new-onset diabetes after transplantation (NODAT) and transplant-associated hyperglycemia (TAH) (NODAT or new-onset impaired glucose tolerance-IGT). We studied 251 consecutive renal transplant South Asian recipients for incidence of NODAT and its risk factors...

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Main Authors: Yogesh N. V. Reddy, Georgi Abraham, Varun Sundaram, Pooja P Reddy, Milly Mathew, Prethivee Nagarajan, Nikita Mehra, A Ramachandran, Asik Ali Mohammed Ali, Yuvaram N. V. Reddy
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2015-01-01
Series:Saudi Journal of Kidney Diseases and Transplantation
Online Access:http://www.sjkdt.org/article.asp?issn=1319-2442;year=2015;volume=26;issue=6;spage=1113;epage=1120;aulast=Reddy
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author Yogesh N. V. Reddy
Georgi Abraham
Varun Sundaram
Pooja P Reddy
Milly Mathew
Prethivee Nagarajan
Nikita Mehra
A Ramachandran
Asik Ali Mohammed Ali
Yuvaram N. V. Reddy
author_facet Yogesh N. V. Reddy
Georgi Abraham
Varun Sundaram
Pooja P Reddy
Milly Mathew
Prethivee Nagarajan
Nikita Mehra
A Ramachandran
Asik Ali Mohammed Ali
Yuvaram N. V. Reddy
author_sort Yogesh N. V. Reddy
collection DOAJ
description Kidney transplant recipients may develop new-onset diabetes after transplantation (NODAT) and transplant-associated hyperglycemia (TAH) (NODAT or new-onset impaired glucose tolerance-IGT). We studied 251 consecutive renal transplant South Asian recipients for incidence of NODAT and its risk factors between June 2004 and January 2009. Pre-transplant glucose tolerance test (GTT) identified non-diabetics (n = 102, IGT-24, NGT-78) for analysis. Baseline immunosuppression along with either cyclosporine (CsA) (n = 70) or tacrolimus (Tac) (n = 32) was given. Patients underwent GTT 20 days (mean) post-transplant to identify NODAT, normal (N) or IGT. TAH was observed in 40.2% of the patients (40% in CsA and 40.6% in Tac) (P = 0.5). NODAT developed in 13.7% of the patients (12.9% in CsA and 15.6% in Tac) (P = 0.5). Overall, Hepatitis C (P = 0.007), human leukocyte antigen (HLA) B52 (P = 0.03) and lack of HLA A28 (A68/69) (P = 0.03) were associated with TAH. In the Tac group, higher Day 1 dosage (P <0.001), HLA A1 (P = 0.04), B13 (P = 0.03) and lack of DR2 (P = 0.004) increased the risk of TAH. In the CsA group, HLA A10 (P = 0.03), failure of triglyceride (P = 0.001) or low-density lipoprotein (LDL) (P = 0.03) to lower or high-density lipoprotein to rise (P = 0.001), and higher post-transplant LDL (P <0.001) and cholesterol levels (P = 0.02) were associated with NODAT or TAH. Post-transplant fasting plasma glucose on Day 1 had sensitivity-54.5%, specificity-50.1%, positive predictive value-18.1% and negative predictive value-84.8% for detecting NODAT. In conclusion, there is a genetic predisposition to NODAT and TAH in South Asia as seen by the HLA associations, and a predisposition exists to the individual diabetogenic effects of Tac and CsA based on HLA type. This could lead to more careful selection of calcineurin inhibitors based on HLA types in the South Asian population.
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spelling doaj.art-6a7e8285c11449d699a9fb80fe3808a22022-12-22T03:19:32ZengWolters Kluwer Medknow PublicationsSaudi Journal of Kidney Diseases and Transplantation1319-24422015-01-012661113112010.4103/1319-2442.168558Is there a genetic predisposition to new-onset diabetes after kidney transplantation?Yogesh N. V. ReddyGeorgi AbrahamVarun SundaramPooja P ReddyMilly MathewPrethivee NagarajanNikita MehraA RamachandranAsik Ali Mohammed AliYuvaram N. V. ReddyKidney transplant recipients may develop new-onset diabetes after transplantation (NODAT) and transplant-associated hyperglycemia (TAH) (NODAT or new-onset impaired glucose tolerance-IGT). We studied 251 consecutive renal transplant South Asian recipients for incidence of NODAT and its risk factors between June 2004 and January 2009. Pre-transplant glucose tolerance test (GTT) identified non-diabetics (n = 102, IGT-24, NGT-78) for analysis. Baseline immunosuppression along with either cyclosporine (CsA) (n = 70) or tacrolimus (Tac) (n = 32) was given. Patients underwent GTT 20 days (mean) post-transplant to identify NODAT, normal (N) or IGT. TAH was observed in 40.2% of the patients (40% in CsA and 40.6% in Tac) (P = 0.5). NODAT developed in 13.7% of the patients (12.9% in CsA and 15.6% in Tac) (P = 0.5). Overall, Hepatitis C (P = 0.007), human leukocyte antigen (HLA) B52 (P = 0.03) and lack of HLA A28 (A68/69) (P = 0.03) were associated with TAH. In the Tac group, higher Day 1 dosage (P <0.001), HLA A1 (P = 0.04), B13 (P = 0.03) and lack of DR2 (P = 0.004) increased the risk of TAH. In the CsA group, HLA A10 (P = 0.03), failure of triglyceride (P = 0.001) or low-density lipoprotein (LDL) (P = 0.03) to lower or high-density lipoprotein to rise (P = 0.001), and higher post-transplant LDL (P <0.001) and cholesterol levels (P = 0.02) were associated with NODAT or TAH. Post-transplant fasting plasma glucose on Day 1 had sensitivity-54.5%, specificity-50.1%, positive predictive value-18.1% and negative predictive value-84.8% for detecting NODAT. In conclusion, there is a genetic predisposition to NODAT and TAH in South Asia as seen by the HLA associations, and a predisposition exists to the individual diabetogenic effects of Tac and CsA based on HLA type. This could lead to more careful selection of calcineurin inhibitors based on HLA types in the South Asian population.http://www.sjkdt.org/article.asp?issn=1319-2442;year=2015;volume=26;issue=6;spage=1113;epage=1120;aulast=Reddy
spellingShingle Yogesh N. V. Reddy
Georgi Abraham
Varun Sundaram
Pooja P Reddy
Milly Mathew
Prethivee Nagarajan
Nikita Mehra
A Ramachandran
Asik Ali Mohammed Ali
Yuvaram N. V. Reddy
Is there a genetic predisposition to new-onset diabetes after kidney transplantation?
Saudi Journal of Kidney Diseases and Transplantation
title Is there a genetic predisposition to new-onset diabetes after kidney transplantation?
title_full Is there a genetic predisposition to new-onset diabetes after kidney transplantation?
title_fullStr Is there a genetic predisposition to new-onset diabetes after kidney transplantation?
title_full_unstemmed Is there a genetic predisposition to new-onset diabetes after kidney transplantation?
title_short Is there a genetic predisposition to new-onset diabetes after kidney transplantation?
title_sort is there a genetic predisposition to new onset diabetes after kidney transplantation
url http://www.sjkdt.org/article.asp?issn=1319-2442;year=2015;volume=26;issue=6;spage=1113;epage=1120;aulast=Reddy
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