Evolution of tacrolimus blood levels and concentration-dose ratios in patients who develop new onset diabetes mellitus after kidney transplantation

Abstract

Summary New onset diabetes mellitus (NODM) affects kidney transplantation outcome. Several risk factors, including immunosuppressive drug levels, are related with NODM development. This analysis evaluates the incidence and risk factors of NODM in kidney transplant patients receiving tacrolimus, taking into account 6‐month blood levels and concentration‐dose ratios (CDRs). Seventy‐six patients under tacrolimus therapy who received a cadaveric renal transplant in our centre and with graft survival higher than 1 year were included in the study. NODM was defined as two fasting plasma glucose values ≥126 mg/dl or symptoms of diabetes plus casual plasma glucose concentrations ≥200 mg/dl throughout the first year. We examined previously reported variables related with NODM development. The incidence of NODM at 12 months was 27.6%. Risk factors for NODM included older age, higher first tacrolimus level, higher body mass index and lower first year weight gain. In multivariate analysis, the first year occurrence of NODM was significantly determined by the first tacrolimus blood level >20 ng/ml and age older than 50 years. CDR remains significantly higher in NODM throughout the 6 months. Older age and a high first tacrolimus blood level are associated with the development of NODM during the first year after kidney transplantation. NODM patients show higher CDR during the first 6 months.

Association of calpain-10 gene polymorphism and posttransplant diabetes mellitus in kidney transplant patients medicated with tacrolimus

“…8,10,11 Some studies had also postulated that higher levels of tacrolimus were associated to an increased risk of PTDM. 21 However, this is not the case in the present study as due to therapeutic monitoring of blood levels of the drug, tacrolimus blood concentrations were similar in both evaluated groups. The results of several prospective studies performed up to date suggest that tacrolimus affects insulin release, probably inhibiting its production, but does not precipitate insulin resistance.…”

New-Onset Diabetes after Kidney Transplantation

“…Although many patients experience considerable weight gain during the first year after transplantation, the incidence of NODAT did not correlate significantly with the amount of weight gain that the patient had during the first posttransplantation year (10,13,15). Influence of weight gain over NODAT can become more evident in long-term studies than in 1-yr studies.…”

“…Older age is the strongest and most consistent risk factor for NODAT in kidney transplantation and is reported in the majority of studies (3,7,8,(11)(12)(13)(14)(15)(16). In a study that included 2078 allograft recipients, Cosio et al (10) showed that those who were older than 45 were 2.9 times more likely to develop diabetes.…”

“…NODAT risk increases linearly for every 1 kg above 45 kg (14). As well as obesity, overweight patients (BMI Ն25 and Ͻ30 kg/m 2 ) also are at risk for developing NODAT (13). In overweight nontransplantation patients with impaired glucose tolerance (IGT), lifestyle modification has been shown to reduce the risk for type 2 diabetes after 4 yr, from 23% in the control group to 11% in the intervention group (21).…”

Posttransplant Increase of Body Mass Index is Associated with New-Onset Diabetes Mellitus after Kidney Transplantation

“…In fact, lifestylechange intervention was reported to be highly effective for preventing type 2 diabetes in the general population (Helmrich et al 1991;Tuomilehto et al 2001;Knowler et al 2002). Body mass index (BMI) is the most frequently used diagnostic indication of obesity, and higher pretransplant BMI has been reported to be an independent risk factor of NODAT (Cosio et al 2005;Rodrigo et al 2005;Bonato et al 2008). However, the effect of increase in BMI on the incidence of NODAT has not yet been established.…”