Glucose Metabolism After Renal Transplantation

Abstract

OBJECTIVEWe 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 METHODSRetrospective 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 m2) for transplant versus nontransplant subjects despite adjustments for age, sex, and BMI (all P < 0.001).CONCLUSIONSGlucose 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.

2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2018

“…Whereas posttransplantation hyperglycemia is an important risk factor for subsequent PTDM, a formal diagnosis of PTDM is optimally made once the patient is stable on maintenance immunosuppression and in the absence of acute infection (100-102). The OGTT is considered the gold standard test for the diagnosis of PTDM (97,98,103,104). However, screening patients using fasting glucose and/or A1C can identify high-risk patients requiring further assessment and may reduce the number of overall OGTTs required.…”

Dynamics of Glucose Metabolism After Kidney Transplantation

“…However, differences in relative contribution compared to a non-transplant population have been reported [5]. As in type 2 diabetes, reduced ß-cell function will eventually result in overt PTDM [5]. This is underlined by the fact that PTDM and type 2 diabetes share several risk genes, most of which affect ß-cell function [9, 10].…”

“…However, differences in relative contribution compared to a non-transplant population have been reported [5]. As in type 2 diabetes, reduced ß-cell function will eventually result in overt PTDM [5].…”

“…As in type 2 diabetes, insulin sensitivity and -secretion are key determinants of glucose homeostasis after transplantation [5-8]. However, differences in relative contribution compared to a non-transplant population have been reported [5].…”

Insulin resistance and beta-cell dysfunction in people with prediabetes according to criteria based on glycemia and glycosylated hemoglobin

“…Use of participants' data for research purposes has been approved by the Hospital Management Committee. Part of the data were already included in previous studies [9,10].…”