title: Is there a genetic predisposition to new-onset diabetes after kidney transplantation?
abstract: 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.
authors.affiliation: Madras Medical Mission Hospital, Chennai, India; Division of Cardiovascular Disease, Mayo Clinic, Rochester, Minnesota, USA, .
authors.forename: Yogesh N V
authors.initials: YN
authors.lastname: Reddy
authors.forename: Georgi
authors.initials: G
authors.lastname: Abraham
authors.forename: Varun
authors.initials: V
authors.lastname: Sundaram
authors.forename: Pooja P
authors.initials: PP
authors.lastname: Reddy
authors.forename: Milly
authors.initials: M
authors.lastname: Mathew
authors.forename: Prethivee
authors.initials: P
authors.lastname: Nagarajan
authors.forename: Nikita
authors.initials: N
authors.lastname: Mehra
authors.forename: A
authors.initials: A
authors.lastname: Ramachandran
authors.forename: Asik Ali Mohammed
authors.initials: AA
authors.lastname: Ali
authors.forename: Yuvaram N V
authors.initials: YN
authors.lastname: Reddy
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006084:Graft Rejection / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D065095:Calcineurin Inhibitors; D006680:HLA Antigens; D016572:Cyclosporine; D016559:Tacrolimus