Abnormal Glucose Metabolism and Metabolic Syndrome in Non-Diabetic Kidney Transplant Recipients Early After Transplantation
Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. Transplantation
(Impact Factor: 3.83).
04/2010; 89(8):1034-9. DOI: 10.1097/TP.0b013e3181d05a90
Abnormal glucose metabolism (AGM) and metabolic syndrome (MS) are individually associated with a poor cardiovascular outcome in kidney transplant recipients. We prospectively studied the relationship between AGM and MS in non-diabetic kidney transplant recipients early after transplantation.
A total of 203 de novo kidney transplant recipients underwent standard 2-hr glucose tolerance test 10 weeks after transplantation. Demographic and clinical characteristics were collected. AGM was defined as impaired fasting glucose, impaired glucose tolerance, and new onset diabetes after transplant according to the WHO criteria, and MS was defined according to the National Cholesterol Education Expert Panel criteria.
Overall, 97 patients (47.8%) met the diagnosis of AGM and 98 patients (48.3%) met the criteria of MS. AGM and MS are highly associated (chi, P<0.001). Fasting plasma glucose levels before the transplant are independent predictors common for AGM and MS. Age predicts AGM with and without MS, whereas body mass index before transplant predicts MS. Patients with impaired glucose tolerance and new-onset diabetes after transplant displayed significant worsening of their fasting plasma glucose levels during the 10-week observational period. MS and the components of MS, but not AGM, were associated with reduced transplant renal function (P=0.002).
The early screening of AGM and MS should be emphasized, and the role of early therapeutic interventions aimed at both conditions explored. The long-term follow-up of these patients will yield more insight on the significance of such findings.
Available from: Germaine Wong
- "The development of metabolic and vascular complications such as post-transplant diabetes mellitus (PTDM), hypertension and dyslipidaemia has contributed to the increased risk of CVD in this population
[4,5]. Abnormal glucose regulation including PTDM and pre-diabetes (impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) is a common complication in non-diabetic renal transplant recipients and is present in 48 to 54% of patients at 10 weeks following kidney transplantation
[6,7]. However, it has been shown that glucose regulation following transplantation is a dynamic process, with the incidence of PTDM and IGT declining from 54% at 10 weeks to 35% at 6 years, likely related to reduction in immunosuppression
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ABSTRACT: Post-transplant diabetes mellitus (PTDM) has been associated with an increased risk of cardiovascular disease (CVD) mortality following kidney transplantation, but the association between pre-diabetes (i.e. impaired fasting glucose and impaired glucose tolerance) and CVD mortality remains unclear. The aim of this study was to assess the association between abnormal glucose regulation and arterial stiffness at 3 and 15 months post-transplantation.
This is a single-centre prospective cohort study of 83 non-diabetic kidney transplant recipients who received a kidney transplant between 2008 and 2011. All patients underwent an oral glucose tolerance test (OGTT - categorised as normal, pre-diabetes or PTDM) and non-invasive measurements of arterial stiffness (aortic pulse wave velocity [PWV] and augmentation index [AIx]) 3 months post-transplantation. A sub-set of patients had repeat OGTT (n = 33) and arterial stiffness measurements (n = 28) at 15 months post-transplant.
Of the 83 patients, 52% (n = 43) had normal glucose regulation, 31% (n = 26) had pre-diabetes and 17% (n = 14) developed PTDM. Compared with recipients with normal glucose regulation, recipients with PTDM (adjusted beta = 5.61, 95% confidence interval [CI] 0.09 to 11.13, p = 0.047) but not those with pre-diabetes (adjusted beta = 3.23, 95%CI -1.05 to 7.51, p = 0.137) had significantly higher AIx 3 months after transplantation. No association was found between glucose regulation and PWV at 3 months after transplantation. There was no association between glucose regulation at 3 or 15 months and AIx and PWV at 15 months in a subset of recipients.
Early onset PTDM is associated with increased systemic vascular stiffness (AIx) but not regional stiffness of large arteries (PWV) suggesting that small vessel dysfunction may be the earliest vascular change seen with PTDM. Thus, measurements of arterial stiffness after transplantation may assist in more accurately stratifying future CVD risk of kidney transplant recipients.
Available from: Adnan Sharif
- "Our previous OGTT-based analysis of TIP study control patients at 3 months posttransplantation, however, showed 84% abnormal glucose metabolism, with 52% NODAT (16). Patients in the TIP study were older than patients in other reports, and all of them had received the more diabetogenic primary immunosuppressant tacrolimus (31) immediately after transplantation, whereas in the described analyses only 12% of patients in a United States cohort (30) and 15% of patients in a Norwegian study (29) received tacrolimus. Moreover, because patients with NODAT have an increased mortality risk (3,32), they could have been lost to cross-sectional analyses. "
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We determined prevalence, risk factors, phenotype, and pathophysiological mechanism of new-onset diabetes after transplantation (NODAT) to generate strategies for optimal pharmacological management of hyperglycemia in NODAT patients.RESEARCH DESIGN AND METHODS
Retrospective cohort study comparing demographics, laboratory data, and oral glucose tolerance test (OGTT)-derived metabolic parameters from kidney transplant recipients versus subjects not receiving transplants.RESULTSAmong 1,064 stable kidney transplant recipients (≥6 months posttransplantation), 113 (11%) had a history of NODAT and 132 (12%) had pretransplant diabetes. In the remaining patients, randomly assigned OGTTs showed a high prevalence of abnormal glucose metabolism (11% diabetes; 32% impaired fasting glucose, impaired glucose tolerance, or both), predominantly in older patients who received tacrolimus as the primary immunosuppressant. Compared with 1,357 nontransplant subjects, stable kidney transplant recipients had lower basal glucose, higher glycated hemoglobin, lower insulin secretion, and greater insulin sensitivity in each of the three subgroups, defined by OGTT 2-h glucose (<140, 140-199, ≥200 mg/dL). These findings were reinforced in linear spline interpolation models of insulin secretion and sensitivity (all P < 0.001) and in another regression model in which the estimated oral glucose insulin sensitivity index was substantially higher (by 79-112 mL/min m(2)) for transplant versus nontransplant subjects despite adjustments for age, sex, and BMI (all P < 0.001).CONCLUSIONS
Glucose metabolism differs substantially between kidney transplant recipients and nontransplant controls. Because impaired insulin secretion appears to be the predominant pathophysiological feature after renal transplantation, early therapeutic interventions that preserve, maintain, or improve β-cell function are potentially beneficial in this population.
Available from: François Becker
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