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

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.

Validation of the association of <i>TCF7L2</i> and <i>SLC30A8</i> gene polymorphisms with post-transplant diabetes mellitus in Asian Indian population

“…Few genetic polymorphisms appeared as negative association, such as SLC30A8, IGFBP2, HHEX, CDKN2A/B, PPARG, KCNJ11, and TCF7L2 (9,21). Our studies showed positive association towards rs7903146 and rs13266634 polymorphisms and not in accordance with the prior studies carried out in PTDM subjects in different ethnicities (9,15,21). The associations of diabetic diseases with rs7903146 and rs13266634 polymorphisms have been carried in Indian population (14,(22)(23)(24)(25)(26)(27)(28)(29).…”

“…synthesis, storage, and secretion (14). Previous studies showed no association of rs13266634 polymorphism with PTDM in different ethnicities (9,15,21), as well with T2DM in Indian population (25,28). Chauhan et al, (27) and our earlier study (14) showed a positive association of rs13266634 polymorphism with PTDM.…”

“…For instance, the associations were established between PTDM and genetic mutations (16) and T2DM genetic polymorphisms, such as PPARG, POR, IGFBP2, ADIPONECTIN, KCNQ1, CALPAIN, and INTERLEUKIN genes (8,10,(17)(18)(19)(20). Few genetic polymorphisms appeared as negative association, such as SLC30A8, IGFBP2, HHEX, CDKN2A/B, PPARG, KCNJ11, and TCF7L2 (9,21). Our studies showed positive association towards rs7903146 and rs13266634 polymorphisms and not in accordance with the prior studies carried out in PTDM subjects in different ethnicities (9,15,21).…”

Hyperparathyroidism and New Onset Diabetes After Renal Transplantation

“…17 Several other risk factors, such as pre-transplant obesity, genetic disposition and certain infections, have also been identified or suggested. 18,22,23,30 Incidence rates of NODAT between 2 and 53% have been reported in the literature. 31 In the present study the one-year cumulative incidence was 15% and the diagnosis was made within 180 days after transplantation in nearly 95% of all cases.…”

“…17 However, several other risk factors such as age, pre-transplant weight, certain infections and genetic predisposition have also been identified or suggested. [18][19][20][21][22][23] To the best of our knowledge, the role of hyperparathyroidism in developing NODAT has not been studied. This association could have important implications in the assessment of the individual patient risk of NODAT and in how to handle hyperparathyroidism in transplanted patients.…”