Pilot Study: Association of Traditional and Genetic Risk Factors and New-Onset Diabetes Mellitus Following Kidney Transplantation

Harini M Chakkera, R. L. Hanson, S. M. Raza, J. K. DiStefano, M. P. Millis, R. L. Heilman, D. C. Mulligan, Kunam Sudhakar Reddy, M. J. Mazur, K. Hamawi, A. A. Moss, K. L. Mekeel, James R Cerhan

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Abstract

Introduction: New-onset diabetes mellitus, which occurs after kidney transplant and type 2 diabetes mellitus (T2DM), shares common risk factors and antecedents in impaired insulin secretion and action. Several genetic polymorphisms have been shown to be associated with T2DM. We hypothesized that transplant recipients who carry risk alleles for T2DM are "tipped over" to develop diabetes mellitus in the posttransplant milieu. Methods: We investigated the association of genetic and traditional risk factors present before transplantation and the development of new-onset diabetes mellitus after kidney transplantation (NODAT). Markers in 8 known T2DM-linked genes were genotyped using either the iPLEX assay or allelic discrimination (AD)-PCR in the study cohort testing for association with NODAT. We used univariate and multivariate logistic regression models for the association of pretransplant nongenetic and genetic variables with the development of NODAT. Results: The study cohort included 91 kidney transplant recipients with at least 1 year posttransplant follow-up, including 22 who developed NODAT. We observed that increased age, family history of T2DM, pretransplant obesity, and triglyceridemia were associated with NODAT development. In addition, we observed positive trends, although statistically not significant, for association between T2DM-associated genes and NODAT. Conclusions: These findings demonstrated an increased NODAT risk among patient with a positive family history for T2DM, which, in conjunction with the observed positive predictive trends of known T2DM-associated genetic polymorphisms with NODAT, was suggestive of a genetic predisposition to NODAT.

Original languageEnglish (US)
Pages (from-to)4172-4177
Number of pages6
JournalTransplantation Proceedings
Volume41
Issue number10
DOIs
StatePublished - Dec 2009

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Kidney Transplantation
Diabetes Mellitus
Type 2 Diabetes Mellitus
Genetic Polymorphisms
Cohort Studies
Logistic Models
Kidney
Genetic Predisposition to Disease
Genes
Obesity
Transplantation
Alleles
Insulin
Transplants
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Pilot Study : Association of Traditional and Genetic Risk Factors and New-Onset Diabetes Mellitus Following Kidney Transplantation. / Chakkera, Harini M; Hanson, R. L.; Raza, S. M.; DiStefano, J. K.; Millis, M. P.; Heilman, R. L.; Mulligan, D. C.; Reddy, Kunam Sudhakar; Mazur, M. J.; Hamawi, K.; Moss, A. A.; Mekeel, K. L.; Cerhan, James R.

In: Transplantation Proceedings, Vol. 41, No. 10, 12.2009, p. 4172-4177.

Research output: Contribution to journalArticle

Chakkera, HM, Hanson, RL, Raza, SM, DiStefano, JK, Millis, MP, Heilman, RL, Mulligan, DC, Reddy, KS, Mazur, MJ, Hamawi, K, Moss, AA, Mekeel, KL & Cerhan, JR 2009, 'Pilot Study: Association of Traditional and Genetic Risk Factors and New-Onset Diabetes Mellitus Following Kidney Transplantation', Transplantation Proceedings, vol. 41, no. 10, pp. 4172-4177. https://doi.org/10.1016/j.transproceed.2009.08.063
Chakkera, Harini M ; Hanson, R. L. ; Raza, S. M. ; DiStefano, J. K. ; Millis, M. P. ; Heilman, R. L. ; Mulligan, D. C. ; Reddy, Kunam Sudhakar ; Mazur, M. J. ; Hamawi, K. ; Moss, A. A. ; Mekeel, K. L. ; Cerhan, James R. / Pilot Study : Association of Traditional and Genetic Risk Factors and New-Onset Diabetes Mellitus Following Kidney Transplantation. In: Transplantation Proceedings. 2009 ; Vol. 41, No. 10. pp. 4172-4177.
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T2 - Association of Traditional and Genetic Risk Factors and New-Onset Diabetes Mellitus Following Kidney Transplantation

AU - Chakkera, Harini M

AU - Hanson, R. L.

AU - Raza, S. M.

AU - DiStefano, J. K.

AU - Millis, M. P.

AU - Heilman, R. L.

AU - Mulligan, D. C.

AU - Reddy, Kunam Sudhakar

AU - Mazur, M. J.

AU - Hamawi, K.

AU - Moss, A. A.

AU - Mekeel, K. L.

AU - Cerhan, James R

PY - 2009/12

Y1 - 2009/12

N2 - Introduction: New-onset diabetes mellitus, which occurs after kidney transplant and type 2 diabetes mellitus (T2DM), shares common risk factors and antecedents in impaired insulin secretion and action. Several genetic polymorphisms have been shown to be associated with T2DM. We hypothesized that transplant recipients who carry risk alleles for T2DM are "tipped over" to develop diabetes mellitus in the posttransplant milieu. Methods: We investigated the association of genetic and traditional risk factors present before transplantation and the development of new-onset diabetes mellitus after kidney transplantation (NODAT). Markers in 8 known T2DM-linked genes were genotyped using either the iPLEX assay or allelic discrimination (AD)-PCR in the study cohort testing for association with NODAT. We used univariate and multivariate logistic regression models for the association of pretransplant nongenetic and genetic variables with the development of NODAT. Results: The study cohort included 91 kidney transplant recipients with at least 1 year posttransplant follow-up, including 22 who developed NODAT. We observed that increased age, family history of T2DM, pretransplant obesity, and triglyceridemia were associated with NODAT development. In addition, we observed positive trends, although statistically not significant, for association between T2DM-associated genes and NODAT. Conclusions: These findings demonstrated an increased NODAT risk among patient with a positive family history for T2DM, which, in conjunction with the observed positive predictive trends of known T2DM-associated genetic polymorphisms with NODAT, was suggestive of a genetic predisposition to NODAT.

AB - Introduction: New-onset diabetes mellitus, which occurs after kidney transplant and type 2 diabetes mellitus (T2DM), shares common risk factors and antecedents in impaired insulin secretion and action. Several genetic polymorphisms have been shown to be associated with T2DM. We hypothesized that transplant recipients who carry risk alleles for T2DM are "tipped over" to develop diabetes mellitus in the posttransplant milieu. Methods: We investigated the association of genetic and traditional risk factors present before transplantation and the development of new-onset diabetes mellitus after kidney transplantation (NODAT). Markers in 8 known T2DM-linked genes were genotyped using either the iPLEX assay or allelic discrimination (AD)-PCR in the study cohort testing for association with NODAT. We used univariate and multivariate logistic regression models for the association of pretransplant nongenetic and genetic variables with the development of NODAT. Results: The study cohort included 91 kidney transplant recipients with at least 1 year posttransplant follow-up, including 22 who developed NODAT. We observed that increased age, family history of T2DM, pretransplant obesity, and triglyceridemia were associated with NODAT development. In addition, we observed positive trends, although statistically not significant, for association between T2DM-associated genes and NODAT. Conclusions: These findings demonstrated an increased NODAT risk among patient with a positive family history for T2DM, which, in conjunction with the observed positive predictive trends of known T2DM-associated genetic polymorphisms with NODAT, was suggestive of a genetic predisposition to NODAT.

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