Abnormal glucose metabolism and metabolic syndrome in non-diabetic kidney transplant recipients early after transplantation.
ABSTRACT 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.
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ABSTRACT: Risk factors associated with the progression from impaired glucose tolerance (IGT) to NIDDM were examined in data from six prospective studies. IGT and NIDDM were defined in all studies by World Health Organization (WHO) criteria, and baseline risk factors were measured at the time of first recognition of IGT. The studies varied in size from 177 to 693 participants with IGT, and included men and women followed from 2 to 27 years after the recognition of IGT. Across the six studies, the incidence rate of NIDDM was 57.2/1,000 person-years and ranged from 35.8/1,000 to 87.3/1,000 person-years. Although baseline measures of fasting and 2-h postchallenge glucose levels were both positively associated with NIDDM incidence, incidence rates were sharply higher for those in the top quartile of fasting plasma glucose levels, but increased linearly with increasing 2-h postchallenge glucose quartiles. Incidence rates were higher among the Hispanic, Mexican-American, Pima, and Nauruan populations than among Caucasians. The effect of baseline age on NIDDM incidence rates differed among the studies; the rates did not increase or rose only slightly with increasing baseline age in three of the studies and formed an inverted U in three studies. In all studies, estimates of obesity (including BMI, waist-to-hip ratio, and waist circumference) were positively associated with NIDDM incidence. BMI was associated with NIDDM incidence independently of fasting and 2-h post challenge glucose levels in the combined analysis of all six studies and in three cohorts separately, but not in the three studies with the highest NIDDM incidence rates. Sex and family history of diabetes were generally not related to NIDDM progression. This analysis indicates that persons with IGT are at high risk and that further refinement of risk can be made by other simple measurements. The ability to identify persons at high risk of NIDDM should facilitate clinical trials in diabetes prevention.Diabetes 05/1997; 46(4):701-10. · 7.90 Impact Factor
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ABSTRACT: Retrospective studies on the prevalence of posttransplant diabetes mellitus (PTDM) in patients on triple-drug immunosuppressive therapy have shown great dispersity, while the incidence of posttransplant impaired glucose tolerance (IGT) is unknown. The aim of our study was to prospectively examine the incidence of posttransplant glucose intolerance and to assess potential risk factors. Glucose intolerance was prospectively examined in 173 consecutive kidney transplant recipients by oral glucose tolerance tests (n=167) or the diagnosis of manifest diabetes mellitus (n=6) at 10 weeks after transplant. We found a high incidence of PTDM (18%) and IGT (31%). Univariate analysis revealed that age, family history of diabetes, HLA-B27 phenotype, DR mismatch, rejection, actual prednisolone dose, total methylprednisolone dose, total steroid dose, cytomegalovirus (CMV) infection, and the use of furosemide were associated with PTDM. Age, prednisolone dose, CMV infection, and the use of beta-blockers were associated with IGT. Gender, body mass index, donor source, and cyclosporine level did not influence glucose tolerance. Prednisolone dose, age, family history of diabetes, CMV infection, and HLA-B27 phenotype were independent predictors of PTDM with the use of multiple stepwise logistic regression analysis. Age, prednisolone dose, and the use of a beta-blocker were associated with IGT in the multivariate model. Both univariate and multivariate linear regression analysis revealed a significant relationship between the 2-hr serum glucose and prednisolone dose. The risk of developing PTDM was 5% per 0.01 mg/kg/day of increase in prednisolone dose. Increased prednisolone dose and older age are strongly associated with the development of posttransplant glucose intolerance.Transplantation 11/1997; 64(7):979-83. · 3.78 Impact Factor
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ABSTRACT: To investigate the mechanism of diabetogenic action of cyclosporin A (CsA), 7 male Wistar albino rats received 10 mg/kg/day of the drug for 4 weeks (CsA). The results were compared with controls (C); blood CsA levels measured weekly remained stable throughout the experiment (mean +/- SEM) (X = 2657.9+/-155.1 ng/ml). Intravenous glucose load (0.75 g/kg) performed after 2 weeks of CsA therapy showed glucose intolerance in treated animals as evaluated by the glucose area under the curve (CsA = 409.2+/-17.8 vs. C = 313.3+/-12.6 umol x ml(-1) x min(-1)) (p < 0.05) with insulin levels being similar in the two groups (CsA = 8603.9+/-1645.5 vs. C = 9571.9+/-828.5 pmol x ml(-1) x min(-1)). After 4 weeks of CsA administration, glucose intolerance was maintained (CsA = 398.6+/-35.6 vs. C = 301.7+/-23.0 umol x ml(-1) x min(-1)) (p < 0.05) associated with a significant decrease in insulin secretion (CsA = 4404.9+/-2392.0 vs. C = 10075.9+/-2861.0 pmol x ml(-1) x min(-1) (p < 0.05). These results suggest that CsA induced a state of insulin resistance preceding the failure of insulin secretion. After 4 weeks, the pancreatic insulin content was also decreased (CsA = 0.7+/-0.1 vs. C = 1.4+/-0.5 mU/mg) (p < 0.05). Maximal insulin binding to isolated adipocytes was not affected by CsA (CsA = 7.4+/-2.6 vs. C = 6.4+/-2.0%), although glucose transport and oxidation decreased after CsA treatment (p < 0.05). In conclusion, glucose intolerance induced by CsA in Wistar albino rats is due to decreased insulin production and impaired insulin action by a post-binding mechanism.Hormone and Metabolic Research 12/1998; 30(11):663-7. · 2.15 Impact Factor