New-onset Diabetes After Transplantation Research Articles

Abstract #1183881: Tacrolimus Induced Hyperosmolar Hyperglycemic State In A Kidney Transplant Recipient

Tacrolimus is a calcineurin inhibitor used for immunosuppression in organ transplant patients. In 74% of organ recipients, it can destroy pancreatic beta-islet cells and create peripheral insulin resistance, thereby causing new onset diabetes after transplant (NODAT). It has been reported to cause diabetic ketoacidosis (DKA), however, its association with hyperosmolar hyperglycemic state (HHS) is not well described. We present here a rare case of HHS as the initial presentation of NODAT due to Tacrolimus.

New-Onset Diabetes after Transplantation (NODAT) in Renal Transplant Recipients, A Retrospective Single Centre Study

Objective: New onset diabetes after transplant (NODAT) is a known post-transplant complication contributing to morbidity and mortality. This study was aimed to find out the frequency of NODAT in kidney disease patients after one year. Methods and subjects: The study was conducted retrospectively on 275 Asian patients who underwent kidney transplant. The demographic and clinical data was evaluated at the time, as well as 3, 6, and 12 months after kidney transplant. The etiology of end-stage renal disease (ESRD) or comorbidities was also documented. Every patient received a combination of Tacrolimus (Tac), Mycophenolate Mofetil (MMF), and Prednisone (Pred) as post-transplant immunosuppression. Patients who developed NODAT were compared with those who did not. RESULTS: One year after the transplantation, the incidence of NODAT was 4.3 percent. Patients diagnosed with NODAT were older (p = 0.001) and had renal failure owing to Chronic glomerulonephritis with hypertension (p = 0.001), according to the results of the univariate analysis. The NODAT group had significantly greater rates of high blood pressure after transplantation (p = 0.01), heart failure (p = 0.02), and dyslipidemia (p = 0.001) than the other groups. Through the use of logistic regression, it was shown that high blood pressure after transplant, and dyslipidemia are all independently linked with NODAT. Conclusion: Asian patients who had high blood pressure and dyslipidemia had a higher incidence of NODAT compared to those who did not have. Keywords: kidney transplantation, prevalence, new-onset diabetes after trasplant

Modeling type 2 diabetes in rats by administering tacrolimus

ABSTRACT The prevalence of diabetes is rapidly increasing. The current number of diagnosed cases is ~422 million, expected to reach ~640 million by 2040. Type 2 diabetes, which constitutes ~95% of the cases, is characterized by insulin resistance and a progressive loss of β-cell function. Despite intense research efforts, no treatments are yet able to cure the disease or halt its progression. Since all existing animal models of type 2 diabetes have serious drawbacks, one is needed that represents the complete pathogenesis, is low cost and non-obese, and can be developed relatively quickly. The aim of this study was to evaluate a low-cost, non-obese model of type 2 diabetes engendered by administering a daily high dose of tacrolimus (an immunosuppressant) to Wistar rats for 4 weeks. The biochemical and antioxidant markers were measured at basal and after the 4-week tacrolimus treatment. At week 4, the values of these parameters closely resembled those observed in human type 2 diabetes, including fasting blood glucose at 141.5 mg/dL, blood glucose greater than 200 mg/dL at 120 min of the glucose tolerance test, blood glucose at varied levels in the insulin tolerance test, and elevated levels of cholesterol and triglyceride. The tacrolimus treatment produced hypoinsulinemia and sustained hyperglycemia, probably explained by the alteration found in pancreatic β-cell function and morphology. This model should certainly be instrumental for evaluating possible type 2 diabetes treatments, and for designing new immunosuppressants that do not cause pancreatic damage, type 2 diabetes, or new-onset diabetes after transplantation (NODAT).

Risk of New-Onset Diabetes after Transplantation among Kidney Transplant Recipients with Cytomegalovirus Infection: A Retrospective Analysis

Background: New-onset diabetes after transplantation (NODAT) is one of the common complications reported in patients with kidney transplant and is associated with risk of infection, poor allograft and patient survival. There is conflicting research literature regarding the role of cytomegalovirus (CMV) infection in increasing the risk of NODAT development. Objective: To assess the risk of development of NODAT in kidney transplant patients with CMV infection Methods: A total of 59 kidney transplant patients were studied from March 2017 to February 2019. NODAT was defined as two readings of fasting plasma glucose of ≥126 mg/dL at three months post-transplant. CMV viral load was also documented. The 12 months post-transplant allograft and patient survival outcomes were also measured. Results: Mean age was 43.4 ± 6.2 years. Nearly one-fourth, 14 (23.7%), of the patients had NODAT. CMV viral load and viremia were high in NODAT group; however, the result did not reach statistical significance. CMV DNA replication was statistically high during 1-6 months post-transplant for NODAT group (P<0.001). Only 7 (11.9%) recipients advanced to symptomatic CMV infection. Also, we found that high CMV viremia load was associated with poor kidney allograft function at 12 months. Conclusions: In summary, this study showed that infection with CMV may not be a risk factor to develop NODAT in patients transplanted with kidney. An elevated CMV viral load may decrease the post-transplant allograft function at 12 months. The prompt diagnosis and timely management of CMV infection could substantially lessen the risk to develop NODAT subsequent worsening of allograft and patient survival. Keywords: Kidney; Transplant; NODAT; New-onset Diabetes; Cytomegalovirus

The Utility of Pre- and Post-Transplant Oral Glucose Tolerance Tests: Identifying Kidney Transplant Recipients With or at Risk of New Onset Diabetes After Transplant.

Background: New onset diabetes after transplant (NODAT) is common in kidney transplant recipients (KTRs). Identifying patients at risk prior to transplant may enable strategies to mitigate NODAT, with a pre-transplant oral glucose tolerance test (OGTT) suggested by the KDIGO 2020 Guidelines for this purpose. Methods: We investigated the utility of pre- and post-transplant OGTTs to stratify risk and diagnose NODAT in a retrospective, single-centre cohort study of all non-diabetic KTRs transplanted between 2003 and 2018. Results: We identified 597 KTRs who performed a pre-transplant OGTT, of which 441 had their post-transplant glycaemic status determined by a clinical diagnosis of NODAT or OGTT. Pre-transplant dysglycaemia was identified in 28% of KTRs and was associated with increasing age (p < 0.001), BMI (p = 0.03), and peritoneal dialysis (p < 0.001). Post-transplant dysglycaemia was common with NODAT and impaired glucose tolerance (IGT) occurring in 143 (32%) and 121 (27%) patients, respectively. Pre-transplant IGT was strongly associated with NODAT development (OR 3.8, p < 0.001). Conclusion: A pre-transplant OGTT identified candidates at increased risk of post-transplant dysglycaemia and NODAT, as diagnosed by an OGTT. Robust prospective trials are needed to determine whether various interventions can reduce post-transplant risk for candidates with an abnormal pre-transplant OGTT.

Remnant lipoprotein cholesterol is associated with incident new onset diabetes after transplantation (NODAT) in renal transplant recipients: results of the TransplantLines Biobank and cohort Studies

BackgroundNew onset diabetes after transplantation (NODAT) is a frequent and serious complication of renal transplantation resulting in worse graft and patient outcomes. The pathophysiology of NODAT is incompletely understood, and no prospective biomarkers have been established to predict NODAT risk in renal transplant recipients (RTR). The present work aimed to determine whether remnant lipoprotein (RLP) cholesterol could serve as such a biomarker that would also provide a novel target for therapeutic intervention.MethodsThis longitudinal cohort study included 480 RTR free of diabetes at baseline. 53 patients (11%) were diagnosed with NODAT during a median [interquartile range, IQR] follow-up of 5.2 [4.1–5.8] years. RLP cholesterol was calculated by subtracting HDL and LDL cholesterol from total cholesterol values (all directly measured).ResultsBaseline remnant cholesterol values were significantly higher in RTR who subsequently developed NODAT (0.9 [0.5–1.2] mmol/L vs. 0.6 [0.4–0.9] mmol/L, p = 0.001). Kaplan-Meier analysis showed that higher RLP cholesterol values were associated with an increased risk of incident NODAT (log rank test, p < 0.001). Cox regression demonstrated a significant longitudinal association between baseline RLP cholesterol levels and NODAT (HR, 2.27 [1.64–3.14] per 1 SD increase, p < 0.001) that remained after adjusting for plasma glucose and HbA1c (p = 0.002), HDL and LDL cholesterol (p = 0.008) and use of immunosuppressive medication (p < 0.001), among others. Adding baseline remnant cholesterol to the Framingham Diabetes Risk Score significantly improved NODAT prediction (change in C-statistic, p = 0.01).ConclusionsThis study demonstrates that baseline RLP cholesterol levels strongly associate with incident NODAT independent of several other recognized risk factors.

Abstract 132: Incidence and predictors of new onset diabetes after transplant (NODAT) in liver transplant recipients

Background: NODAT (New onset Diabetes after Transplant) is associated with multiple complications in liver transplant patients which has to be diagnosed and treated early to prevent graft failure and cardiovascular morbidity and mortality.Aims and Objectives: To know the incidence and predictors of NODAT.Methodology: This was retro-prospective study of non-Diabetic recipients who underwent Liver Transplantation at Yashoda Hospital, Secundarabad from January 2020 to May 2021. Follow-up duration was 6 months. Total 65 patients were enrolled. All the relevant data was collected and appropriate statistical tests were applied.Results: Total incidence of NODAT in our study was 29.2%. Among them 47.36% were transient NODAT and 52.67% were persistent NODAT. Factors significantly associated with occurrence of NODAT were: Type of Transplant (Living donor liver transplant v/s Deceased donor liver transplant), Donor CT LAI, Presence of IFG, Presence of Post-Operative Hyperglycemia, Pre transplant Magnesium & Immediate post-operative Magnesium level, Post-Operative Albumin, Trough Tacrolimus level At 3 Months, Tacrolimus and steroid dose at 3 months.Conclusions: NODAT is significant entity to be addressed. Robust strategy should be in place for screening of NODAT. Choosing donor with Higher CT LAI and minimizing Tacrolimus level could be effective strategy for prevention of NODAT.

POS-764 ANALYSIS OF CORRELATION BETWEEN GLUCOCORTICOID RECEPTOR POLYMORPHISMS AND NEW-ONSET DIABETES IN RENAL RECIPIENTS

New-onset diabetes after transplantation (NODAT) is one of the severe metabolic complications after transplantation. Glucocorticoid receptor is encoded by NR3C1 gene and it seems that polymorphisms in this gene lead to sensitivity increase to insulin. Therefore, the aim of the study was to evaluate four common polymorphisms in the NR3C1 gene in kidney recipients with NODAT.

New-onset Diabetes after Renal Transplant and Associated Factors.

To assess the frequency and time of onset of new-onset diabetes after transplant (NODAT) and its associated factors. Observational study. Department of Nephrology, Bahria International Hospital, Lahore, Pakistan, from April 2016 to April 2018. NODAT was diagnosed according to American Diabetes Association Criteria with fasting plasma glucose >126 mg/dl or random plasma glucose >200 mg/dl. Those with pre-existing diabetes and follow-up duration less than 12months, were excluded. Patients were divided in two groups: with and without NODAT, for statistical comparison. The study included 115 patients, 101 were males and the median age was 35.0 (29.0-46.0) years. During the one-year period of follow-up, 28 (24.3%) patients developed NODAT. The mean time of onset of NODAT was 5.3 ± 3.6 months. Family history of diabetes was positive in 46% patients in NODAT group, which was significantly higher as compared to 5.7% in non-NODAT group with p-value of <0.001, which is significant. All patients with more than three HLA mismatches developed NODAT. The mean fasting glucose levels (FPG) before transplant in NODAT group was 96.6 ± 15.4 mg/dl, which was significantly higher than FPG of non-NODAT group, where it was 80.5 ± 12.2 mg/dl. It was interesting to note that 35.7% of hepatitis patients developed NODAT as compared to 6 % in non-NODAT group with p = 0.001. NODAT was observed in 24.3% patients. The pre-transplant FPG, family history of diabetes, increased HLA mismatches, and hepatitis C infection were the major associated factors. Key Words: New onset diabetes after transplant, Fasting plasma glucose, Renal transplant.

TCF7L2 rs7903146 Is Associated With Increased Risk of New-Onset Diabetes After Transplant: A Meta-analysis of Literature

Single nucleotide polymorphisms may influence the risk of development of new-onset diabetes after transplant (NODAT), a post-transplant clinical complication that is often implicated in allograft rejection and mortality. We performed a meta-analysis of association between transcription factor 7-like-2 (TCF7L2) rs7903146 and risk of NODAT. A systematic search was conducted using PubMed and ScienceDirect electronic databases for studies published between January 2001 and January 2021. Case-control or cohort studies reporting association between NODAT (diagnosis based on American Diabetes Association criteria) and TCF7L2 rs7903146 were included. MetaGenyo was used for meta-analysis (random-effects model). Pooled odds ratios with 95% confidence intervals were reported to evaluate the strength of association. Two reviewers independently screened for articles. A total of 6 case-control studies were included for full-text review and quantitative analysis after screening for eligibility. Genotypic distributions were in Hardy-Weinberg equilibrium for included studies. All articles reported statistically significant association of TCF7L2 rs7903146 for risk of NODAT except for 1 study. There was moderate heterogeneity among studies (I2=60.6%). Pooled analysis revealed 51% odds of developing NODAT with TCF7L2 rs7903146 T allele (allele contrast model: odds ratio, 1.51; 95% confidence interval, 1.13-2.02; P=.005). The present meta-analysis demonstrated association between TCF7L2 variant rs7903146 and risk of developing NODAT. This finding suggest clinical implications for individuals undergoing kidney transplant.

Impact of Pretransplant and New-Onset Diabetes After Transplantation on the Risk of Major Adverse Cardiovascular Events in Kidney Transplant Recipients: A Population-based Cohort Study.

Pretransplant diabetes and new-onset diabetes after transplant (NODAT) are known risk factors for vascular events after kidney transplantation, but the incidence and magnitude of the risk of major adverse cardiovascular events (MACE) and cardiac deaths remain uncertain in recent era. A population cohort study of kidney transplant recipients identified using data from linked administrative healthcare databases from Ontario, Canada. The incidence rates of MACE (expressed as events with 95% confidence interval [95% CI] per 1000 person-years were reported according to diabetes status of pretransplant diabetes, NODAT, or no diabetes. Extended Cox regression model was used to examine the association between diabetes status, MACE, and cardiac death. Of 5248 recipients, 1973 (38%) had pretransplant diabetes, and 799 (15%) developed NODAT with a median follow-up of 5.5 y. The incidence rates (95% CI) of MACE for recipients with pretransplant diabetes, NODAT, and no diabetes between 1 and 3 y posttransplant were 38.1 (32.1-45.3), 12.6 (6.3-25.2), and 11.8 (9.2-15.0) per 1000 person-years, respectively. Compared with recipients with pretransplant diabetes, recipients with NODAT experienced a lower risk of MACE (adjusted hazard ratio, 0.59; 95% CI, 0.47-0.74) but not cardiac death (adjusted hazard ratio, 0.97; 95% CI, 0.61-1.55). The rate of MACE and cardiac death was lowest in patients without diabetes. Patients with pretransplant diabetes incur the greatest rate of MACE and cardiac deaths after transplantation. Having NODAT also bears high burden of vascular events compared with those without diabetes, but the magnitude of the increased rate remains lower than recipients with pretransplant diabetes.

Association of serum adiponectin and leptin levels with renal function in kidney transplant recipients with or without new-onset diabetes after transplantation.

PurposeTo evaluate serum adiponectin and leptin concentration in new‐onset diabetes after transplantation (NODAT) and non‐NODAT patients and association with renal function in kidney transplant recipients (KTRs).Patients and methodsA study of 314 consecutive adults KTRs divided into four groups: 236 individuals without NODAT who had renal insufficiency (RI; n = 56) or normal renal function (n = 180) and 78 patients with NODAT who had RI (n = 17) or normal renal function (n = 61). NODAT was diagnosed based on venous fasting blood glucose or HbA1c with the criteria of the American Diabetes Association. Renal insufficiency was defined according to KDOQI 2002 guidelines.ResultsIn the NODAT group, the median level of serum adiponectin was lower than that of non‐NODAT one (30 µg/ml vs 37.15 µg/ml, p < 0.001); in contrast, the median leptin concentration was higher (4.27 ng/ml vs 4.05 ng/ml, p = 0.024). In the RI group, both median serum adiponectin and leptin levels were higher than those of non‐RI one (Adiponectin: 40.01 µg/ml vs 33.7 µg/ml; Leptin: 4.51 ng/ml vs 3.91 ng/ml, p < 0.001 both). We found that BMI was related to both adiponectin and leptin levels in both NODAT, non‐NODAT, and all subject groups, based on univariate and multivariate linear regression analysis.ConclusionNew‐onset diabetes after transplantation, BMI, and renal insufficiency were affected to the serum level of adiponectin and leptin in KTRs.

Early Steroid Withdrawal After Kidney Transplantation in Patients at Risk for New-Onset Diabetes After Transplantation

New-onset diabetes after transplantation (NODAT) is a serious complication after kidney transplantation because of worse graft survival and increased risk of cardiovascular events. It is partly induced by immunosuppressive therapies such as corticosteroids. This study aimed to assess whether early corticosteroid withdrawal on day 4 (early steroid withdrawal [ESW] group) could prevent the development of NODAT within 2 years posttransplantation while maintaining good graft and patient survival rates. This was an observational, single-center, retrospective study. All patients received an induction therapy of antithymocyte globulin or basiliximab and maintenance therapy of tacrolimus/mycophenolate mofetil/corticosteroids. Patients were either weaned off corticosteroids on day 4 (ESW group) or were maintained on corticosteroids for at least 3 months (standard group). NODAT was defined as the initiation of any oral hypoglycemic agent or insulin at 3 months and up to 2 years posttransplantation in previously nondiabetic recipients. Between January, 1, 2010, and December 14, 2014, 492 recipients were included in this study; 88 received the ESW strategy, and 404 received the standard strategy. Age and body mass index (BMI) were significantly higher in the ESW group. The incidence of NODAT was 36.8% in the ESW group and 8.8% in the standard group (odds ratio [OR], 47.5; P < .001). Compared with a matched sample from the standard group that had the same probability to benefit from ESW at baseline, ESW was still associated with a significantly increased risk of NODAT (OR, 4.41; P=.018). Among recipients with a BMI >25 kg/m2, the ESW strategy significantly decreased the risk of NODAT compared with the standard strategy (OR, 0.07; P=.013). Safety endpoints (eg, acute rejection, de novo-specific antibodies, graft function/survival) did not differ between groups. Despite a reassuring safety profile, ESW on day 4 after kidney transplantation only had a marginal effect on the incidence of NODAT.

Association between preoperative lipid profiles and new‐onset diabetes after transplantation in Chinese kidney transplant recipients: A retrospective cohort study

BackgroundThis study investigated the association between the preoperative lipid profiles and new‐onset diabetes after transplantation (NODAT) in Chinese kidney transplant recipients (KTRs).MethodsIn this study, of 1140 KTRs registered between January 1993 and March 2018 in Zhongshan Hospital, Fudan University, 449 were enrolled. Clinical data, obtained through a chart review of the patient records in the medical record system, were evaluated, and NODAT was diagnosed based on the American Diabetes Association guidelines. Multivariate Cox regression analysis was conducted to determine whether the preoperative lipid profiles in KTRs were independently associated with NODAT incidence. The preoperative lipid profiles were analyzed as continuous variables and grouped into tertiles. Smooth curve fitting was used to confirm the linear associations.ResultsDuring a median follow‐up of 28.03 (interquartile range 12.00–84.23) months, 104 of the 449 (23.16%) participants developed NODAT. The multivariate model analysis, adjusted for all potential covariates, showed that increased values of the following parameters were associated with NODAT (hazard ratio, 95% confidence interval): preoperative total cholesterol (TC; 1.25, 1.09–1.58, p = 0.0495), low‐density lipoprotein cholesterol (LDL‐C; 1.33, 1.02–1.75, p = 0.0352), non‐high‐density lipoprotein cholesterol (non‐HDL‐C; 1.41, 1.09–1.82, p = 0.0084), TC/HDL‐C (1.28, 1.06–1.54, p = 0.0109), and non‐HDL‐C/HDL‐C (1.26, 1.05–1.52, p = 0.0138). However, the association between the preoperative triglyceride, HDL‐C, or TG/HDL‐C and NODAT was not significant.ConclusionsPreoperative TC, LDL‐C, non‐HDL‐C, TC/HDL‐C, and non‐HDL‐C/HDL‐C were independent risk factors for NODAT.

Efficacy and Safety of SGLT2 Inhibitors in Diabetic Kidney Transplant Patients: Review of the Current Literature

Introduction: SGLT2 inhibitors are oral hypoglycemic medications used in type 2 diabetes mellitus (T2DM). They act by blocking glucose and sodium reabsorption in the proximal renal tubules. In patients with T2DM and cardiovascular disease, SGLT2 inhibitors have been shown to improve glycemic control, promote weight loss, and reduce major adverse cardiovascular events (MACE). They have also been shown to have favorable renal outcomes in patients with chronic kidney disease (CKD) reducing albuminuria and progression to end-stage renal disease; however, all studies have excluded kidney transplant patients. The objective of this review was to determine the efficacy and safety of SGLT2 inhibitors in the kidney transplant population. Methods: We conducted a literature review to identify studies which assessed the use of SGLT2 inhibitors in kidney transplant patients with either T2DM or new onset diabetes after transplant (NODAT). The outcomes assessed included blood pressure, glycemic control, body weight, kidney function, proteinuria and complications. Results: Nine studies, which included 144 patients, were extracted for review. These included x4 case series, x3 cohort studies, x1 randomized control trial (RCT), and x1 case report. The largest study was a prospective RCT from Norway, which assessed empagliflozin versus placebo in 44 patients. Majority of patients had NODAT (n=92) or T2DM (n=50). All patients had estimated glomerular filtration rate (eGFR) >30mL/min/1.73m2 and HbA1C >6.5%. The most commonly used SGLT2 inhibitors were empagliflozin (n=82), canagliflozin (n=34), and dapagliflozin (n=28). SGLT2 inhibitor use in kidney transplant patients was found to demonstrate a small or non-significant reduction in blood pressure, modest improvement in glycemic control and decrease in insulin resistance, and moderate-to-significant weight reduction. It also resulted in stable graft function and one study demonstrated a reduction in proteinuria. The most common adverse effect was urinary tract infection (n=13). There were no cases of diabetic ketoacidosis or development of new ischemic lower limb ulcerations or amputations. Conclusion: Our literature review suggests beneficial outcomes of SGLT2 inhibitor use in diabetic kidney transplant patients, with no significant adverse effects or complications. Given the limited evidence in this population, we are launching a prospective study in kidney transplant patients with either T2DM or NODAT, and with eGFR ≥30mL/min/1.73m2, to assess the efficacy and safety of SGLT2 inhibitor use in this population. To our knowledge, this will be the first prospective study in Canada assessing SGLT2 inhibitor use in diabetic kidney transplant patients.

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.

POS-363 new onset - diabetes mellitus Within 1 Year After Kidney Transplantation in Tunisian Cohort Study:risk factors

New-Onset Diabetes After Transplantation (NODAT) is serious metabolic complication which is associated with impaired graft and recipient survival, mainly due to cardiovascular events and infectious complications. The purpose of this study is to determine the incidence of NODAT and identify risk factors within the first year after kidney transplantation in one center.

Predictive Value of Triglyceride Glucose Index for the Development of New-Onset Diabetes Mellitus Following Heart Transplantation

<h3>Purpose</h3> Diabetes mellitus (DM) is a major cause of morbidity and mortality following heart transplantation (HT), with 35% being affected within 5 years. Identification of patients at risk for the development of DM could enable prevention and proper intervention. The Triglyceride Glucose (TyG) index is considered a surrogate marker of insulin resistance and is an early indicator for developing type 2 DM in the non-transplant population. We investigated the association between the TyG index and new-onset diabetes after transplantation (NODAT). <h3>Methods</h3> A total of 158 non-DM HT patients were included in the study. The risk of NODAT was assessed according to the 3-month TyG index, calculated as ln[fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. The endpoint was NODAT, defined according to the diagnostic criteria of the American Diabetes Association. <h3>Results</h3> The overall prevalence of NODAT was 20%. The TyG index in the NODAT group was significantly higher than that for the no-NODAT group (9.4 vs 8.7, p <0.001). A TyG index of 8.9 had a sensitivity of 78%, with a specificity of 70% for the prediction of NODAT. Kaplan-Meier survival analysis showed that NODAT rate was significantly higher for patients with a high vs a low TyG index (40 vs 8%, p >0.001, Fig.). Consistently, multivariable analysis, adjusted for age, gender, BMI, immunosuppression, hypertension, and dyslipidemia, showed that a high TyG index was independently associated with a significant 3.3-fold increased risk for NODAT (p = 0.03, Fig.). Patients with a high TyG index had significantly higher rates of peripheral vascular disease (21 vs 8%, p = 0.04) and allograft vasculopathy (48 vs 19%, p <0.001) than patients with a low TyG index. <h3>Conclusion</h3> The TyG index, a simple measure reflecting insulin resistance, might help identify individuals at high risk for developing NODAT. The implications of early interventions, using the TyG index as a marker, on the risk for NODAT and clinical outcomes, should be evaluated.

Impact of New Onset Diabetes after Transplantation (NODAT) on Heart Transplantation Recipients

Impact of New Onset Diabetes after Transplantation (NODAT) on Heart Transplantation Recipients

Analysis of the frequency of single nucleotide polymorphisms in cytokine genes in patients with New Onset Diabetes After Transplant

New Onset Diabetes After Transplantation (NODAT) is a serious metabolic complication. While β-cell dysfunction is considered the main contributing factor in the development of NODAT, the precise pathogenesis is not well understood. Cytokines are thought to be involved in the inflammation of islet β-cells in diabetes; however, few studies have investigated this hypothesis in NODAT. A total of 309 kidney transplant recipients (KTRs) were included in this study. An association between kidney transplants, and the development of diabetes after transplant (NODAT) was investigated. Comparison was made between KTRs who develop diabetes (NODAT cases) or did not develop diabetes (control), using key cytokines, IL-6 G (− 174)C, macrophage mediator; IL-4 C (− 490)T, T helper (Th)-2 cytokine profile initiator; Th-1 cytokine profile initiator interferon-γ T (+ 874) A gene and TGF β1 C (+ 869) T gene polymorphisms were investigated. The genes were amplified using well-established polymerase chain reaction (PCR) techniques in our laboratory. Compared to the AA and AT genotypes of interferon gamma (IFNG), there was a strong association between the TT genotype of IFNG and NODAT kidney transplant recipients (KTRs) versus non-NODAT KTRs (p = 0.005). The AA genotype of IFNG was found to be predominant in the control group (p = 0.004). Also, significant variations of IL6 G (− 174) C, IL-4 C (− 590) T, interferon-γ T (+ 874) A gene and transforming growth factor β1 C (+ 869) T may contribute to NODAT. Our data is consistent with theTh-1/T-reg pathway of immunity. Further larger pan Arab studies are required to confirm our findings.