Risk factors and incidence of posttransplant diabetes mellitus in Mexican kidney recipients

BACKGROUND: Many risk factors are associated with the development of posttransplant diabetes mellitus (PTDM), which has adverse effects on graft and patient survival. We report the incidence and risk factors associated with the development of PTDM in Mexican kidney recipients. METHODS: In a retrospective cohort study, we included kidney transplants performed between January 1, 1994 and December 31, 2000; all patients were followed up for at least 1 year posttransplantation. PTDM was defined as fasting blood glucose >126 mg/dL on at least two occasions. Statistical analysis included estimation of crude relative risk (RR) with 95% confidence intervals (CI). Adjusted RR and 95% CI by logistic regression were used. RESULTS: We studied 522 kidney recipients. Fifty three (10.1%) cases of PTDM were identified in this cohort. Cumulative dosage of prednisone (PDN) >13 g (RR 7.6, 95% CI 1.5-16.3 p <0.0001) and the presence of >or=1 acute rejection episodes (RR 3.7, 95% CI 1.2-11.6 p <0.001 were independent risk factors associated with the development of PTDM. Obesity (RR 2.6, 95% CI 0.8-8.7, p = 0.083) and age range of 40-49 years (RR 2.0; 95% CI 0.6-7.2, p = 0.093) were identified as marginal risk factors. CONCLUSIONS: The incidence of PTDM in kidney recipients was 10.1% in our population. Cumulative PDN dosage and presence of >or=1 acute rejection episodes were independent risk factors for the development of PTDM. These results are consistent with prior studies of the diabetogenic effect of the PDN. The relationship between acute rejection and PTDM deserves further investigation in order to learn more about the role that inflammatory mechanisms may play in this association.     

Long-term efficacy and safety of anti-hyperglycaemic agents in new-onset diabetes after transplant: Results from outpatient-based 1-year follow-up and a brief review of treatment options

Background and aimsEvaluation of long-term efficacy and safety of various anti-hyperglycaemic agents (AHA) for glycaemic control in NODAT, in stable kidney transplant recipients (KTRs) during 1-year outpatient follow-up.MethodsWe collected FPG, PPG, HbA1c, serum creatinine, eGFR, blood tacrolimus level, hypoglycaemia and body weight values from an existing database of KTRs diagnosed to have NODAT. Those newly initiated on AHA over 3 months post-transplant; received standard triple immunosuppressive therapy; and followed up for 1-year after referral, were included.ResultsIn ninety-five patients’ (Male = 65), mean decrease at 1-year from baseline in FPG (185.01 ± 62.11 mg/dL), PPG (293.21 ± 85.23 mg/dL) and HbA1c (8.48 ± 1.08%) was 67.09, 126.11 and 1.4 respectively (p < 0.0001). At 1-year, mean HbA1c was 7.08 ± 0.38%, ninety-one patients achieving HbA1c ≤ 7.5%. Fifty-two patients received oral combination therapy based on linagliptin/metformin/repaglinide/gliclazide, 19 received insulin-based regimen, and 24 received linagliptin monotharapey. Thirty patients reported hypoglycaemia (10 with gliclazide and 15 with insulin) and fifty patients gained body-weight at 1-year. Mean serum creatinine and eGFR significantly improved by 0.29 and 15.77 from baseline of 1.56 ± 0.62 mg/dL and 53.95 ± 16.10 mL/min/1.73 m² respectively.ConclusionsSignificant proportion of NODAT patients achieved long-term glycemic control with improved renal function. Combination therapy was needed in most within 1-year. Linagliptin monotherapy was effective, without producing hypoglycaemia or weight gain.     

Role of sex in post-transplant diabetes mellitus development: Are men and women equal?

Introduction

Sex differences are defined as biology-linked differences between women and men that occur through the sex chromosomes and their effects on organ systems.

Impaired Insulin Sensitivity as an Underlying Mechanism Linking Hepatitis C and Posttransplant Diabetes Mellitus in Kidney Recipients

Aim of this study was to investigate the mechanism/s associating hepatitis C virus (HCV) infection and posttransplant diabetes mellitus in kidney recipients. Twenty HCV‐positive and 22 HCV‐negative kidney recipients, 14 HCV‐positive nontransplant patients and 24 HCV‐negative nontransplant (healthy) subjects were analyzed. A 3‐h intravenous glucose tolerance test was performed; peripheral insulin sensitivity was assessed by minimal modeling. Pancreatic insulin secretion, hepatic insulin uptake, pancreatic antibodies and proinflammatory cytokines in serum (tumor necrosis factor‐α, intereukin‐6, high‐sensitive C‐reactive protein) were also assessed. HCV‐positive recipients showed a significantly lower insulin sensitivity as compared to HCV‐negative recipients (3.0 ± 2.1 vs. 4.9 ± 3.0 min^?1.μU.mL^{? 1}.10⁴, p = 0.02), however, insulin secretion and hepatic insulin uptake were not significantly different. Pancreatic antibodies were negative in all. HCV status was an independent predictor of impaired insulin sensitivity (multivariate analysis, p = 0.008). The decrease of insulin sensitivity due to HCV was comparable for transplant and non‐transplant subjects. No significant correlation was found between any of the cytokines and insulin sensitivity. Our results suggest that impaired peripheral insulin sensitivity is associated with HCV infection irrespective of the transplant status, and is the most likely pathogenic mechanism involved in the development of type 2 diabetes mellitus associated with HCV infection.     

The importance of different immunosuppressive regimens in the development of posttransplant diabetes mellitus

Solid-organ transplantation is the optimal long-term treatment for most patients with end-stage organ failure. After solid-organ transplantation, short-term graft survival significantly improved (1). However, due to chronic allograft nephropathy and death with functioning graft, long-term survival has not prolonged remarkably (2). Posttransplant immunosuppressive medications consist of one of the calcineurin inhibitors in combination with mycophenolate mofetil (MMF) or azathioprine (Aza) and steroids. All of them have different adverse effects, among which posttransplant diabetes mellitus (PTDM) is an independent risk factor for cardiovascular (CV) events and infections causing the death of many transplant patients and it may directly contribute to graft failure (3). According to the criteria of the American Diabetes Association (4), diabetes mellitus (DM) is defined by symptoms of diabetes (polyuria and polydipsia and weight loss) plus casual plasma glucose concentration ≥ 11.1 mmol/L or fasting plasma glucose (FPG) ≥ 7.0 mmol/L or 2-h plasma glucose level ≥ 11.1 mmol/L following oral glucose tolerance test (OGTT). This metabolic disorder occurring as a complication of organ transplantation has been recognized for many years. PTDM, which is a combination of decreased insulin secretion and increased insulin resistance, develops in 4.9/15.9% of liver transplant patients, in 4.7/11.5% of kidney recipients, and in 15/17.5% of heart and lung transplants [cyclosporine A (CyA)/tacrolimus (Tac)-based regimen, respectively] (5). Risk factors of PTDM can be divided into non-modifiable and modifiable ones (6), among which the most prominent is the immunosuppressive therapy being responsible for 74% of PTDM development (7). Emphasizing the importance of the PTDM, numerous studies have determined the long-term outcome. On the basis of these studies, graft and patient survival is tendentiously (8) or significantly (9, 10) decreased for those developing PTDM.     

The Clinical Course and Outcomes of Post-Transplantation Diabetes Mellitus after Heart Transplantation

The aim of this study was to describe in more detail the predisposition, natural course, and clinical impact of post-transplantation diabetes mellitus (PTDM) after heart transplantation (HT). The characteristics and clinical outcomes of 54 patients with PTDM were compared with those of 140 patients without PTDM. The mean age of PTDM patients was significantly higher than controls (48.9 ± 9.3 vs 38.6 ± 13.3 yr, respectively, P = 0.001), and ischemic heart disease was a more common indication of HT (20.4% [11/54] vs 7.1% [10/140], respectively, P = 0.008). In multivariate analysis, only recipient age (odds ratio, 1.80; 95% confidence interval, 1.35-2.40; P = 0.001) was associated with PTDM development. In 18 patients (33%), PTDM was reversed during the follow-up period, and the reversal of PTDM was critically dependent on the time taken to develop PTDM (1.9 ± 1.0 months in the reversed group vs 14.5 ± 25.3 months in the maintained group, P = 0.005). The 5-yr incidence of late infection (after 6 months) was higher in the PTDM group than in the control group (30.4% ± 7.1% vs 15.4% ± 3.3%, respectively, P = 0.031). However, the 5-yr overall survival rate was not different (92.9% ± 4.1% vs 85.8% ± 3.2%, respectively, P = 0.220). In conclusion, PTDM after HT is reversible in one-third of patients and is not a critical factor in patient survival after HT.