New-onset Diabetes After Transplantation In Renal Transplant Recipients Research Articles

Serum hs-CRP measured prior transplantation predicts of new-onset diabetes after transplantation in renal transplant recipients

BackgroundTo assess the incidence of new-onset diabetes after transplantation (NODAT) for the first year post-transplantation and the predictive value of high-sensitivity C-reactive Protein (hs-CRP) before transplantation for NODAT prediction in kidney transplantation patients. Material and methodsA study of 251 consecutive adult end-stage kidney disease patients transplanted kidneys from living donors, follow-up during the first year to find NODAT. We diagnosed NODAT based on blood glucose or HbA1c following to the criteria of the American Diabetes Association. ResultsThe ratio of NODAT was 12.4%. The mean age, mean BMI, the proportion of arteriosclerosis, and the median hs-CRP level in NODAT group were significantly higher than those of non-NODAT group with p < 0.05. Age, BMI and serum hs-CRP had a predictive value for NODAT (Age: AUC = 0.62, p < 0.05, BMI: AUC = 0.626, hs-CRP: AUC = 0.748, p < 0.001). ConclusionSerum hs-CRP level measured prior transplantation is a good predictor for NODAT in renal transplant recipients.

HDL Cholesterol Efflux Predicts Incident New-Onset Diabetes After Transplantation (NODAT) in Renal Transplant Recipients Independent of HDL Cholesterol Levels.

In renal transplant recipients (RTRs), new-onset diabetes after transplantation (NODAT) is a frequent and serious complication limiting survival of graft and patient. However, the underlying pathophysiology remains incompletely understood. In vitro and in preclinical models, HDL can preserve β-cell function, largely by mediating cholesterol efflux, but this concept has not been evaluated in humans. This study investigated whether baseline cholesterol efflux capacity (CEC) in RTRs is associated with incident NODAT during follow-up. This prospective longitudinal study included 405 diabetes-free RTRs with a functioning graft for >1 year. During a median (interquartile range) follow-up of 9.6 (6.6-10.2) years, 57 patients (14.1%) developed NODAT. HDL CEC was quantified using incubation of human macrophage foam cells with apolipoprotein B-depleted plasma. Baseline CEC was significantly lower in patients developing NODAT during follow-up (median 6.84% [interquartile range 5.84-7.50%]) compared with the NODAT-free group (7.44% [6.46-8.60%]; P = 0.001). Kaplan-Meier analysis showed a lower risk for incident NODAT with increasing sex-stratified tertiles of HDL efflux capacity (P = 0.004). Linear regression analysis indicated that CEC is independently associated with incident NODAT (P = 0.04). In Cox regression analyses, CEC was significantly associated with NODAT (hazard ratio 0.53 [95% CI 0.38-0.76]; P < 0.001), independent of HDL cholesterol levels (P = 0.015), adiposity (P = 0.018), immunosuppressive medication (P = 0.001), and kidney function (P = 0.01). Addition of CEC significantly improved the predictive power of the Framingham Diabetes Risk Score (P = 0.004). This study establishes HDL CEC as a strong predictor of NODAT in RTRs, independent of several other recognized risk factors.

Plasma Malondialdehyde and Risk of New-Onset Diabetes after Transplantation in Renal Transplant Recipients: A Prospective Cohort Study.

New-onset diabetes after transplantation (NODAT) is a frequent complication in renal transplant recipients (RTR). Although oxidative stress has been associated with diabetes mellitus, data regarding NODAT are limited. We aimed to prospectively investigate the long-term association between the oxidative stress biomarker malondialdehyde (measured by high-performance liquid chromatography) and NODAT in an extensively phenotyped cohort of non-diabetic RTR with a functioning graft ≥1 year. We included 516 RTR (51 ± 13 years-old, 57% male). Median plasma malondialdehyde (MDA) was 2.55 (IQR, 1.92–3.66) µmol/L. During a median follow-up of 5.3 (IQR, 4.6–6.0) years, 56 (11%) RTR developed NODAT. In Cox proportional-hazards regression analyses, MDA was inversely associated with NODAT, independent of immunosuppressive therapy, transplant-specific covariates, lifestyle, inflammation, and metabolism parameters (HR, 0.55; 95% CI, 0.36–0.83 per 1-SD increase; p < 0.01). Dietary antioxidants intake (e.g., vitamin E, α-lipoic acid, and linoleic acid) were effect-modifiers of the association between MDA and NODAT, with particularly strong inverse associations within the subgroup of RTR with relatively higher dietary antioxidants intake. In conclusion, plasma MDA concentration is inversely and independently associated with long-term risk of NODAT in RTR. Our findings support a potential underrecognized role of oxidative stress in post-transplantation glucose homeostasis.

Prevalence and Predictors of "New-onset Diabetes after Transplantation" (NODAT) in Renal Transplant Recipients: An Observational Study.

Objective:New-onset diabetes after transplantation (NODAT) develops frequently after renal transplant. The study aims at the prevalence of NODAT, predictors for developing it and therapeutic glycemic responses in NODAT.Materials and Methods:Consecutive renal transplant recipients excluding Diabetic Kidney Disease (DKD) or pretransplant diabetes were evaluated. Forty-three out of 250 persons were found to have NODAT. Ninety age-matched transplant recipients from the rest were recruited as control. Fasting blood sugar (FBS), HbA1c, lipid profile, and trough tacrolimus level (T0) were examined in all. HOMA IR C-peptide and HOMA-beta C-peptide were calculated.Results:Prevalence of NODAT in renal transplant recipients was 17.2% (43/250). Twenty-four (55.8%) developed early NODAT (<1 year) and 19 (44.2%) developed late NODAT (>1 year). Significantly higher pretransplant body mass index (BMI) (kg/m2) (P < 0.001), waist circumference (WC) (cm) (P < 0.001), pretransplant cholesterol (mg%) (P = 0.04), triglyceride (mg%) (P < 0.001), and FBS (mg%) (P < 0.001) were found in NODAT compared with non-NODAT. Trough tacrolimus (ng/mL) was found to be higher in NODAT (10.2 vs. 5.37, P < 0.001). Though HOMA IR was not found to be different between groups, HOMA-beta C-peptide was low in NODAT compared with non-NODAT (P = 0.03). Predictors of NODAT were WC [odds ratio (OR) = 01.15] and trough tacrolimus level (OR = 1.316). Best cut-off of WC for predicting NODAT was 87.5 cm for male and 83.5 cm for female. Best cut-off of T0 was 8.5 ng/mL. In NODAT, 9.3% were treated by lifestyle modification, 67.4% by oral hypoglycemic agents, 11.6% by insulin, and 11.6% by combined insulin and oral antidiabetic agents with HbA1c <7%.Conclusion:NODAT in renal transplant recipients is more common in those with higher pretransplant BMI, WC, pretransplant total cholesterol, triglyceride, and FBS. Beta-cell secretory defect is more relevant as etiological factor rather than insulin resistance. Higher WC and trough tacrolimus level above 8.5 ng/mL may be important factors for predicting NODAT.

Interleukin-2 receptor antagonists: Protective factors against new-onset diabetes after renal transplantation.

The aim of the present study was to examine the association between interleukin-2 receptor antagonists (IL-2Ra) and new-onset diabetes after transplantation (NODAT) among renal transplant recipients (RTRs). Between January 1993 and March 2014, 915 patients underwent renal transplantation at Zhongshan Hospital. In all, 557 RTRs were included in the present retrospective cohort study. The incidence of NODAT in this cohort was determined and multivariate Cox regression analysis was used to evaluate the risk factors for NODAT and to show the association between IL-2Ra use and NODAT development among RTRs. The cumulative incidence of NODAT was compared between groups treated with or without IL-2Ra. The mean ±SD postoperative follow-up was 5.08 ±3.17 years. The incidence of NODAT at the end of follow-up was 20.3%. After adjusting for potential confounders in the multivariate logistic regression (i.e. age, sex, body mass index, history of smoking, family history of diabetes, duration of dialysis, type of dialysis, donor type, recovery of graft function, acute rejection, hepatitis B or C or cytomegalovirus infection, fasting plasma glucose levels before and 1 week after transplantation, preoperative total cholesterol and triglyceride levels, daily dose of glucocorticoid, immunosuppressive regimen type, and immunosuppressant concentration after transplantation), IL-2Ra use was found to be related to a reduced incidence of NODAT. Use of IL-2Ra is associated with protection against the development of NODAT in RTRs.

High serum PCSK9 is associated with increased risk of new-onset diabetes after transplantation in renal transplant recipients

OBJECTIVE New-onset diabetes after transplantation (NODAT) is a major complication in renal transplant recipients (RTRs). Cholesterol metabolism has been linked to diabetes development. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is crucial in LDL receptor regulation. Its association with NODAT is unknown. We prospectively determined the association between serum PCSK9 levels and NODAT development and then with all-cause mortality, cardiovascular mortality, and renal graft failure. RESEARCH DESIGN AND METHODS In a university setting, nondiabetic RTRs recruited between 2001 and 2003 with a functional graft for ≥1 year were eligible. Serum PCSK9 was measured by ELISA. Cox proportional hazards analysis was used to assess the association of PCSK9 with the development of NODAT, all-cause mortality, cardiovascular mortality, and graft failure. RESULTS In 453 RTRs (age 51 ± 12 years, 56% male; 6.1 [2.7–11.7] years after transplantation), serum PCSK9 was 107.1 ± 43.4 μg/L. During a median follow-up of 10 years, 70 RTRs developed NODAT, 123 died, and 59 developed graft failure. NODAT occurred more frequently in the upper PCSK9 tertile (23%) versus the lowest two PCSK9 tertiles (12%; P CONCLUSIONS Circulating PCSK9 is associated with NODAT in RTRs. The PCSK9 pathway may contribute to the pathogenesis of NODAT.

Efficacy and safety of sitagliptin for the treatment of new-onset diabetes after renal transplantation.

New-onset diabetes after transplantation (NODAT) is a common comorbidity after renal transplantation. Though metformin is the first-line agent for the treatment of type 2 diabetes, in renal transplant recipients, metformin is frequently avoided due to concerns about renal dysfunction and risk for lactic acidosis. Therefore, alternative first-line agents for the treatment of NODAT in renal transplant recipients are needed. Sitagliptin, a dipeptidyl-peptidase-4 (DPP-4) inhibitor, has a low incidence of hypoglycemia, is weight neutral, and, in a small study, did not affect immunosuppressant levels. However, long-term sitagliptin use for the treatment of NODAT in kidney transplant recipients has not been studied. We retrospectively analyzed renal transplant recipients diagnosed with NODAT and treated with sitagliptin to assess safety and efficacy. Twenty-two patients were started on sitagliptin alone. After 12 months of followup, 19/22 patients remained on sitagliptin alone with a significant improvement in hemoglobin A1c. Renal function and immunosuppressant levels remained stable. Analysis of long-term followup (32.5 ± 17.8 months) revealed that 17/22 patients remained on sitagliptin (mean hemoglobin A1c < 7%) with 9/17 patients remaining on sitagliptin alone. Transplant-specific adverse events were rare. Sitagliptin appears safe and efficacious for the treatment of NODAT in kidney transplant recipients.

Pre-transplant HbA1c level as an early marker for new-onset diabetes after renal transplantation

New-onset diabetes after transplantation (NODAT) is a common complication in renal transplant (RT) patients. The clinical significance of pre-transplant HbA1c level remains unclear in RT patients. Thus, we investigated the predictive role of pre-transplant HbA1c levels for the NODAT diagnosed in 1 year after renal transplantation. Two hundred and four RT patients older than 18 years were analyzed. NODAT diagnosis during the 1-year follow-up after RT was based on the 2003 modified criteria of the ADA. HbA1c level was measured at pre-transplantation period and every 3 months after RT. Mean age was 39.3 ± 10.7 (20-73) years and 36 % were female. Mean pre-transplant HbA1c level was 4.9 ± 0.5 % (4.0-6.4 %). Pre-transplant HbA1c level was positively correlated with age, pre-transplant body mass index (BMI) and cholesterol level. Fifty-four patients (25.9 %) developed NODAT and 33.8 % had impaired fasting blood glucose levels. Patients with NODAT were significantly older and had higher pre-transplant BMI and HbA1c than those without. Use of Tacrolimus was also higher in patients with NODAT. In stepwise logistic regression analysis, pre-transplant HbA1c level was an independent predictor for the development on NODAT (OR = 4.63, 95 % CI: 2.09-10.2, p < 0.001) together with age, Tacrolimus-based regimen and pre-transplant fasting blood glucose level. Assessment of pre-transplant HbA1c levels may be a valuable tool for early diagnosis of NODAT in RT recipients.

Association of Genetic Polymorphisms of Interleukins With New-Onset Diabetes After Transplantation in Renal Transplantation

New-onset diabetes after transplantation (NODAT) is a serious metabolic complication. Although β-cell dysfunction is considered the main contributing factor in the development of NODAT, the precise pathogenesis has not been identified. Although several cytokines have been suggested to be involved in the inflammation of islet beta cells in diabetes mellitus, only rarely have studies examined β-cell dysfunction in NODAT. Therefore, we examined the association between NODAT and 18 single nucleotide polymorphisms (SNPs) located within the 10 genes of interleukins (IL) or their receptors, which might be related with β-cell dysfunction after kidney transplantation. A total of 306 renal transplants recipients were included without a history of diabetes. We analyzed the association between NODAT development and a panel of 18 SNPs within 10 genes of IL or their receptors. In terms of allele frequencies, rs2069763*T (IL-2), rs1494558*A and rs2172749*C (IL-7R), and rs4819554*A (IL-17R) were significantly higher in patients with NODAT. Eleven SNPs among 18 (61.1%) were significantly associated with NODAT development after adjusting for age, sex, and tacrolimus usage. They include IL-1B (rs3136558), IL-2 (rs2069762), IL-4 (rs2243250, rs2070874), IL-7R (rs1494558, rs2172749), IL-17RE (rs1124053), IL-17R (rs2229151, rs4819554), and IL-17RB (rs1043261, rs1025689). The data suggest that inflammation of islet β cells might play a crucial role in the pathogenesis of NODAT in renal transplantation recipients. In particular, significant variations of IL-7R, IL-17E, IL-17R, and IL-17RB, which was recently reported to be associated with type 1 diabetes mellitus, could be associated with the pathogenesis of NODAT in renal transplant recipients.

Hypomagnesemia and the risk of new-onset diabetes after liver transplantation

New-onset diabetes after transplantation (NODAT) is a frequent complication after liver transplantation and has a negative impact on both patient and graft survival. In analogy with the previous finding of an association between posttransplant hypomagnesemia and NODAT in renal transplant recipients, the relation between both pretransplant and posttransplant hypomagnesemia and NODAT was studied in liver transplant recipients (LTRs). One hundred sixty-nine adult LTRs (>18 years old) without diabetes who underwent transplantation between 2004 and 2009 were studied (mean age = 52.11 ± 12.6 years, proportion of LTRs who were male = 67.5%, body mass index = 25.5 ± 4.4 kg/m², proportion receiving tacrolimus = 90.0%). NODAT was defined according to the American Diabetes Association criteria. The association of NODAT with both pretransplant and posttransplant serum magnesium (Mg) was examined. Overall, 52 of 169 patients (30.8%) developed NODAT, and 57.7% of these (30 patients) were treated with antidiabetic drugs. Both pretransplant Mg levels and Mg levels in the first month after transplantation were lower in patients developing NODAT (P = 0.008 and P = 0.001, respectively). A multivariate regression model (adjusted for weight, pretransplant glucose levels, hyperglycemia in the first week after transplantation, gender, hepatitis C, and corticosteroid dosing) demonstrated both pretransplant Mg levels (hazard ratio = 0.844 per 0.1 mg/dL increase, 95% confidence interval = 0.764-0.932, P = 0.001) and posttransplant Mg levels (hazard ratio = 0.659, 95% confidence interval = 0.518-0.838, P = 0.001) to be independent predictors of NODAT together with age, biopsy-proven acute rejection, and cytomegalovirus (CMV) infection in the first year after transplantation. In conclusion, pretransplant hypomagnesemia and early posttransplant hypomagnesemia are independent predictors of new-onset diabetes after liver transplantation. Other risk factors are age, biopsy-proven acute rejection, and CMV infection.

Posttransplantation Hypomagnesemia and Its Relation with Immunosuppression as Predictors of New-Onset Diabetes after Transplantation

New-onset diabetes after transplantation (NODAT) is a frequent complication and has an impact on patient and graft survival. Hypomagnesemia is common in both renal transplant recipients and in diabetics. This study examines the relationship between hypomagnesemia, NODAT and the type of immunosuppression in renal transplant recipients. We conducted a retrospective single-center analysis (2002-2008) in order to assess NODAT the first year posttransplantation as defined by American Diabetes Association criteria. Serum magnesium (Mg) levels were defined as the median of all Mg levels registered during the first month posttransplantation. Patients with NODAT (N = 75; 29.5%) versus non-NODAT had lower Mg levels (p < 0.001). Patients with an Mg level < versus > or = 1.9 mg/dL showed a faster development of NODAT (log-rank p < 0.001). Mg levels were lower in patients on calcineurin inhibitors (CNI) versus no CNI patients (p < 0.001). Mg levels, albumin, BMI, triglycerides, posttransplantation hyperglycemia, tacrolimus levels and the use of sirolimus were predictors of NODAT in the multivariate analysis. Hypomagnesemia was an independent predictor of NODAT in renal transplant recipients. We confirm that the use of CNI is associated with NODAT, but, to a large extent, this effect seems attributable to the induction of hypomagnesemia. After adjustment for Mg, sirolimus was also associated with NODAT.